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Development of Nanocomposites for Bone Grafting
Abstract
This article reviews nanocomposites focusing on their impact and recent trends in the field of bone grafting. Although autogenous- and allogeneic-bone grafts have been used for a long time in bone therapies, there is still a donor shortage and infection risk. As an alternative, synthetic biomaterials have been developed and clinically used as bone grafts, but most of them differ substantially from natural bone either compositionally or structurally. It remains a great challenge to design an ideal bone graft that emulates nature’s own structure. Owing to the composition and structural similarity to natural bone, most of the current investigations involve the use of nanocomposites, particularly hydroxyapatite/collagen system, as promising bone grafts, but it is surprising that none of the reports review the rationale and design strategy of such nanocomposites in detail for the benefit of researchers. Accordingly, this article addresses the state-of-the-art of those nanocomposites and provides suggestions for future research and development. This review provides an overview of the nanocomposite strategy of bone, bone grafting, synthetic approaches to bone structure, development of nanocomposites from the conventional monolithic biomaterials, and recently developed processing conditions for making nanocomposites. The review is expected to be useful for readers to gain an in-sight on the state-of-the-art of nanocomposites as a new class of synthetic bone grafts.
... Partial flexibility coupled with the superior strength of natural biomineralized tissues (bones and teeth) are attributed to the presence of bioorganic polymers (predominantly collagen type I fibers) coupled with the natural ceramic (largely a poorly crystalline ionsubstituted calcium-deficient hydroxyapatite (CDHA) phase, referred to as 'bioapatite')refer to Table 1 [18][19][20][21][22]. In bones, elastic collagen fibers align with the primary direction of tension. ...
... With regard to CaPO4-based formulations, various methods have been realized to combine matrix and dispersion components to form biocomposites. For example, mechanical blending or mixing, ball milling, compounding, compression, and casting into a polymer-solvent solution followed by solvent evaporation, e.g., by freeze-drying, dispersion of CaPO4 particles, or whisking into a liquid monomer, followed by polymerization, a melt extrusion of CaPO4/polymer mixtures, and co-precipitation or co-deposition, as well as a rapid prototyping, selective laser sintering, and 3D printing [22,37,[170][171][172][173]. Four-dimensional printing, in which the resulting 3D shape is able to morph into different forms in response to environmental stimulus, with the fourth dimension being the timedependent shape change after the printing, is used as well [174]. ...
... In the case of CaPO4 biocomposites with metals, a powder metallurgy approach [201,202] combining direct ink writing with liquid pressure infiltration [203], as well as various types of additive manufacturing [204,205], can be used. The details of various production methods are well described in other publications [22,37,117,170,171]. Furthermore, additional types of preparation techniques are briefly mentioned below when describing the individual CaPO4-based formulations. ...
The goal of this review is to present a wide range of hybrid formulations and composites containing calcium orthophosphates (abbreviated as CaPO4) that are suitable for use in biomedical applications and currently on the market. The bioactive, biocompatible, and osteoconductive properties of various CaPO4-based formulations make them valuable in the rapidly developing field of biomedical research, both in vitro and in vivo. Due to the brittleness of CaPO4, it is essential to combine the desired osteologic properties of ceramic CaPO4 with those of other compounds to create novel, multifunctional bone graft biomaterials. Consequently, this analysis offers a thorough overview of the hybrid formulations and CaPO4-based composites that are currently known. To do this, a comprehensive search of the literature on the subject was carried out in all significant databases to extract pertinent papers. There have been many formulations found with different material compositions , production methods, structural and bioactive features, and in vitro and in vivo properties. When these formulations contain additional biofunctional ingredients, such as drugs, proteins, enzymes , or antibacterial agents, they offer improved biomedical applications. Moreover, a lot of these formulations allow cell loading and promote the development of smart formulations based on CaPO4. This evaluation also discusses basic problems and scientific difficulties that call for more investigation and advancements. It also indicates perspectives for the future.
... Permanent implants, like hip or temporary biodegradable implants, and knee prostheses, like pins and screws, are two categories of orthopedic metallic implants [2]. Stainless steel, cobalt-chromium alloys, and titanium have all been utilized to create durable implants [3,4]. Nonetheless, the utilization of enduring metal implants [5-7] may give rise to certain issues. ...
... Mg and its alloys possess mechanical properties such as elastic module (41)(42)(43)(44)(45) and density (1.74-1.84 g/cm 3 ), which are comparable to those of bone (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) GPa, 1.8-2.1 g/cm 3 ). Then, this issue is substantially lower when compared to other biodegradable materials like zinc (Zn) based alloys, and iron-manganese (Fe-Mn) [2]. ...
... Mg and its alloys possess mechanical properties such as elastic module (41)(42)(43)(44)(45) and density (1.74-1.84 g/cm 3 ), which are comparable to those of bone (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) GPa, 1.8-2.1 g/cm 3 ). Then, this issue is substantially lower when compared to other biodegradable materials like zinc (Zn) based alloys, and iron-manganese (Fe-Mn) [2]. ...
... Calcium phosphate based materials are the most popular bioactive ceramics for skeletal reconstructions because their compositions are close to the mineral part of bone [2][3][4][5][6]. Unfortunately, this group of bioceramics exhibits cannot be used as heavily loaded bearing applications because of their poor mechanical properties [2,5]. ...
... In recent years, nanomaterials have received much attention from various researchers to the development of modern health care industry and have improved the quality of human life. Prostheses and implants are being developed from nanostructured materials with the unique properties that can lead to novel tissue engineering [3,5]. In this research, Nanocrystalline hydroxyapatite (HA) powder was prepared from natural buffalo bone by a high speed vibro-milling method and then calcine at various temperatures. ...
... Thus, it can be confirmed that hydroxyapatite nanopowder is high purity and from table 1 can find the ratio to molar calcium to phosphorus was 1.66, which was close to the 1.67 stoichiometric value of pure hydroxyapatite. It's have been maintained above that HA is a class of calcium phosphate based ceramics which exhibits good properties as biomaterial, such as biocompatibility, bioactivity, osteoconductivity, direct bonding to bone, etc [1][2][3][4][5][6]8]. Many authors reported to a wide range of available calcium phosphates which there are potential formulation depended on the relation between the Ca/P ratio, acidity and solubility [1,8]. ...
The preparation of hydroxyapatite nanopowders in this experiment demonstrated a novel method for milling of animal bone powder to nanoparticle size prior to calcination. The buffalo bone was deproteinized by hot water before it was dried at 200°C for 24 h. The resulting product was crushed into small pieces and milled in a ball mill pot for 24 h. After that, the bone powders were ground by a high speed vibro-milling method with various milling times. Characteristics of the powders were investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDS). The experimental results of SEM showed that the shape of the buffalo bone particles was regular with the particle size less than 100 nm from using high speed vibro-milling time of 2 h. The buffalo bone nanopowder were calcined at various temperatures. XRD and SEM results showed that material obtained is a HA according to JCPDS file-9432 pattern in a 1.66 Ca/P molar ratio at calcination temperature of 600°C. The average diameter of powder less than 100 nm.
... Spondylosyndesis procedures also indicate the unmet requirement for massive autologous bone grafting procedures, which has augmented the most conventional in-patient treatment over the last two decades [23,24]. Nonetheless, its value is severely compromised by its limited availability and donor site morbidity [25]. Reviewing new bone restoration strategies is the need of the hour, the significance of which is driven by the excruciating pain correlated with bone injury and the rising therapeutic and socio-economic shortcomings. ...
... Different imaging techniques used as theragnostic tools for visualizing bone tissue, adapted from[14,25]. ...
Nanomaterial-based tissue engineering strategies are precisely designed and tweaked to contest specific patient needs and their end applications. Though theragnostic is a radical term very eminent in cancer prognosis, of late, theragnostic approaches have been explored in the fields of tissue remodulation and reparation. The engineering of theragnostic nanomaterials has opened up avenues for disease diagnosis, imaging, and therapeutic treatments. The instantaneous monitoring of therapeutic strategy is expected to co-deliver imaging and pharmaceutical agents at the same time, and nanoscale carrier moieties are convenient and efficient platforms in theragnostic applications, especially in soft and hard tissue regeneration. Furthermore, imaging modalities have extensively contributed to the signal-to-noise ratio. Simultaneously, there is an accumulation of high concentrations of therapeutic mediators at the defect site. Given the confines of contemporary bone diagnostic systems, the clinical rationale demands nano/biomaterials that can localize to bone-diseased sites to enhance the precision and prognostic value for osteoporosis, non-healing fractures, and/or infections, etc. Furthermore, bone theragnostics may have an even greater clinical impact and multimodal imaging procedures can overcome the restrictions of individual modalities. The present review introduces representative theragnostic polymeric nanomaterials and their advantages and disadvantages in practical use as well as their unique properties.
... The prediction ability was evaluated by the mean absolute error (MAE) and Pearson's correlation coefficient (r). [23] Ca/P ratio ≤ 1.67 [7,23] Interaction with ions HCO 3 − , Cl − , F − , Na + , K + , Mg 2+ , etc. [24] Interaction with organic additives Glutathione (GSH/GSSG), DA, GLU n , CH 3 COOH (HAc), LAC, acidic amino acids (Asp and Glu), citrate, etc. [14][15][16][17][18][19] Interaction with biomolecules Collagen Non-collagenous proteins (osteocalcin, etc.) [24,25] Geological apatite ...
... The prediction ability was evaluated by the mean absolute error (MAE) and Pearson's correlation coefficient (r). [23] Ca/P ratio ≤ 1.67 [7,23] Interaction with ions HCO 3 − , Cl − , F − , Na + , K + , Mg 2+ , etc. [24] Interaction with organic additives Glutathione (GSH/GSSG), DA, GLU n , CH 3 COOH (HAc), LAC, acidic amino acids (Asp and Glu), citrate, etc. [14][15][16][17][18][19] Interaction with biomolecules Collagen Non-collagenous proteins (osteocalcin, etc.) [24,25] Geological apatite ...
Apatite is the principal inorganic component of biological hard tissues such as bone and teeth, and thus is essential to the existence of vertebrate life. Because carbonate species and chloride ions are ubiquitous in the fluids of vertebrate life forms, and these species are known to compete with phosphate species, it is critical to understand the influence of these anions on the nucleation of biological apatite. In this study, the important roles of carbonate and chloride ions in mediating inorganic calcium phosphate (CaP) phase nucleation are revealed both theoretically and experimentally. Theoretical investigations suggest that the Ca-O coordination number is an important descriptor for the nucleation of CaP and the interface interaction of the CaP-additive. Positive surface charges on the outermost Ca2+ ions of CaP clusters could attract carbonate species and Cl− ions, promoting the formation of CaP phase. In the presence of carbonate species and Cl− ions, the crystallization of hydroxyapatite (HA) from its precursor brushite (DCPD) has been observed in our experimental studies. The Cl− ion-doped B-type HA is proposed to be the most likely biological apatite based on equilibrium oxygen isotope fractionation and vibrational spectroscopic analysis. The insight gained here may help rationalize the control of biomineralization, and will guide the synthesis of anion-doped biological functional apatite materials.
... This means a faster and better integration of the implant to the tissue. [41][42][43] It is also thought that the dense structures observed in the EDX analysis originated from the content of HA and rich content of expanded perlite. ...
... Increased surface area also positively affects bone formation. 36,41,43 ...
This study was aimed to coat a hybrid bioceramic composite onto Ti 6 Al 4 V by using hydrothermal method. The Hybrid bioceramic composite for coating was prepared by reinforcing different rations of expanded perlite (EP) and 5 wt.% chitosan into synthesized Hydroxyapatite (HA). Coating was performed at 1800°C for 12 hours. The coated specimens were gradually subjected to a sintering at 6000°C for 1 hour. For in vitro analysis, the specimens were kept in Ringer’s solution for 1, 10, and 25 days. All specimens were examined by SEM, EDX, FTIR, and surface roughness analyses for characterizing. It was concluded that as the reinforcement ratio increased, there was an increase in coating thickness and surface roughness. The optimum reinforcement ratio for expanded perlite can be 10 wt.% (A3-B3). With increasing ratio of calcium (Ca) and phosphate (P) (Ca/P), the surface becomes more active in body fluid and then observed the formation of the hydroxycarbonate apatite (HCA) layer. As the waiting time increased, there was an increase in the formation of an apatite structure.
... Current advances in bone substitutes began with studies by Barth and Ollier in the 1890s, who tested different materials for bone replacement in animals for the first time. Over the past four decades, a variety of materials from metals, ceramics, polymers and their composites have been developed and successfully used for bone grafting (Murugan and Ramakrishna, 2005). ...
... This enhances osteointegration with a favorable host immune reaction. In this regard, hydroxyapatite-coated titanium alloys introduced and are widely used in orthopedic surgery (Murugan and Ramakrishna, 2005). ...
Successful bone tissue engineering strategies require 3D scaffolds with controllable properties tailored to the intended clinical applications. The scaffold as a temporary substrate for cells to live and grow, must be degraded over time and replaced with the host tissue gradually. However, despite remarkable advances in bone tissue engineering, adjusting the rate of scaffold degradation with the ability of host tissue to regenerate, is still one of the main challenges. To date, most studies on bone tissue engineering have addressed the role of scaffold properties in cell differentiation and bone regeneration, and scaffold degradation has received less attention. For this reason, an understanding of bone tissue engineering materials and their degradation process is valuable if we are to exploit their potential for the regeneration of bone defects. In this review, we specifically have focused on bone scaffold materials. Bone scaffold materials can be degraded through hydrolytic, oxidative, enzymatic, stimuli-assisted, and cell-mediated reactions. In various studies, chemical composition, structure, surface modification and fabrication method of scaffolds have been introduced as influencing factors in the degradation of scaffolds. Herein, not only the degradation mechanisms of materials used in bone scaffolds have been discussed, but also the approaches used by researchers to control the rate of degradation are pointed out.
... Their versatility makes them suitable for various aspects of bone tissue engineering. Ongoing research on PNCs will help address the challenges and demands of bone tissue engineering [143][144][145]. Antibacterial activity [180] Content courtesy of Springer Nature, terms of use apply. ...
Polymer nanocomposites (PNCs) are strengthened by including nanoparticles at a nanoscale. Due to their extraordinary properties, the two-dimensional nanomaterials of 2D are increasingly being regarded as nanofillers in PNCs. An overview of the development of 2D nanomaterial-based PNCs, including manufacturing methods, structural applications, and bio-medical applications such as drug delivery, tissue engineering, gene therapy, cancer therapy, and dental composites, is provided in this review. Nanoparticles may be synthesised with a variety of techniques, for example in situ polymerisation, sol–gel processing, mixed melted materials, and composite solutions. The properties of PNCs have been enhanced by including graphene and other 2D nanomaterials, which enable them to be used in energy generation, storage applications as well as tissue engineering. More recently, the introduction of biological functionalities by combining polymers and 2D nanomaterials has opened new possibilities for these advanced nanocomposites in tissue engineering applications. Specifically, because of their increased cell adhesion, growth, and proliferation, 2D nanomaterial-based polymer composites have shown potential as scaffolds for both soft tissue regeneration and hard tissue engineering. Overall, innovative biomedical applications result from synergistic interactions between the polymer matrix and 2D nanomaterials.
Graphical Abstract
... These properties are attributed to the structure of bone, which forms a matrix with collagen, whereas biological apatite acts as an inorganic phase. 4,5 Recently, bone repair materials mimicking this structure have attracted substantial attention from scholars. These bone repair materials primarily consist of biopolymers and inorganic ceramics. ...
Objectives
Despite being an important research topic in oral biomaterials, few studies have demonstrated the differences between poly(d,l-lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and poly(d,l-lactic acid)/hydroxyapatite (PDLLA/HA). In this study, PLGA/HA and PDLLA/HA scaffolds were prepared using three-dimensional (3D) printing technology and implanted into radius defects in rabbits to assess their effects on bone regeneration.
Methods
In this study, 6 mm × 4 mm bone defects were generated in the bilateral radii of rabbits. 3D-printed PLGA/HA and PDLLA/HA scaffolds were implanted into the defects. X-ray imaging, micro-computed tomography, and hematoxylin–eosin staining were performed to observe the degradation of the materials, the presence of new bone, and bone remodeling in the bone defect area.
Results
The PLGA/HA scaffolds displayed complete degradation at 20 weeks, whereas PDLLA/HA scaffolds exhibited incomplete degradation. Active osteoblasts were detected in both groups. The formation of new bone, bone marrow cavity reconstruction, and cortical bone remodeling were better in the PLGA/HA group than in the PDLLA/HA group.
Conclusions
PLGA/HA scaffolds performed better than PDLLA/HA scaffolds in repairing bone defects, making the former scaffolds more suitable as bone substitutes at the same high molecular weight.
... Up to now, a variety of scaffolds biomaterials have been developed, [4][5][6][7] including bioactive ceramics (e.g., MAO, [8] HA, [9][10][11] ), biodegradable polymers (e.g., PLA, [12] BDSPs [13] ), and biodegradable metals (e.g., Mg, [14][15][16] Zn, [17] Ti [18,19] ). It is worth noting that Mg alloys have attracted extensive attention owing to special features in mechanical properties [20,21] and biological functions, [22] such as the close elastic modulus and density with human cortical bone, [23,24] good biodegradability and biocompatibility. ...
Porous Mg alloys scaffolds are considered as an attractive strategy for bone repair due to their good biodegradability, biocompatibility, and suitable mechanical properties. In this study, porous Mg–1Zn–1Ca–xMn (x = 0, 0.2, 0.5, 0.8) scaffolds with cubic pore structure are prepared, and the size of main pore and interconnected pores of the scaffolds are predicted to be 355–450 and 30–50 μm, respectively. Among the four scaffolds, Mg–1Zn–1Ca–0.8Mn scaffold possesses good mechanical properties, with a maximum yield strength of 27.1 and an elastic modulus of 0.66 GPa. However, Mg–1Zn–1Ca–0.5Mn scaffold exhibits the optimal corrosion resistance with a corrosion rate 1.02 mm year⁻¹ after 5 days immersion in Hank's solution. This is mainly attributed to α‐Mn phase, which is uniformly distributed on the substrate and uniformly degraded.
... Scaffold materials can be broadly categorized into natural, and synthetic (157). Biomaterials can be classified into metal, ceramic, polymer, and composite (161). The advantages and disadvantages of each material should be taken into consideration before utilizing them for OMF hard or soft tissue regeneration and based on the desired functionality of the material on a specific tissue. ...
Oral and maxillofacial (OMF) defects are not limited to humans and are often encountered in other species. Reconstructing significant tissue defects requires an excellent strategy for efficient and cost-effective treatment. In this regard, tissue engineering comprising stem cells, scaffolds, and signaling molecules is emerging as an innovative approach to treating OMF defects in veterinary patients. This review presents a comprehensive overview of OMF defects and tissue engineering principles to establish proper treatment and achieve both hard and soft tissue regeneration in veterinary practice. Moreover, bench-to-bedside future opportunities and challenges of tissue engineering usage are also addressed in this literature review.
... Generally, in addition to porosity and structure, also volume fraction, shape and dimension of HAp particles strongly influence the mechanical properties of composite scaffolds. Moreover, it has been proved that nanocrystalline HAp (nHAp) offers better results than microcrystalline HAp with respect to osteoblast adhesion, differentiation and proliferation, as well as biomineralization [9,10]. Pek et al. [6] successfully prepared collagen nanoapatite composite scaffold by freeze-drying a collagen slurry mixed with carbonated apatite (CAP) and HAp nanocrystals as inorganic component. ...
Natural bone ECM is a hierarchical nanocomposite made of an inorganic phase deposited within an organic matrix. In order to mimic the bone highly organized hybrid structure and functionality, strategies that allow assembling ceramic and polymer phase can be applied. To this aim, we investigated an insitu growth method able to nucleate a nanoHydroxyapatite (nHAp) phase into and around the interconnected porous structure of chitosan sponges. By increasing the calcium and phosphate concentration in the meta-stable solution used for the nHAp nucleation, the inorganic phase raised proportionally, in the range 10%-30% wt. In order to be compared with nHAp loaded scaffolds, pure chitosan samples have been produced by cross-linking biopolymer with arginine. Moreover, nHAp loaded samples, containing the 20 % wt of inorganic phase have been prepared by simply mixing low crystalline nHAp powders with the chitosan gel. The in situ nucleation method highlighted evident advantages in terms of nanophase distribution and mechanical performances with respect to a merely mixing procedure.
... Metal matrix composites are primarily used due to their load-bearing abilities and high mechanical properties, which make them preferable to polymer and ceramic composites [1,2]. Cobalt-chromium, titanium, and stainless steel alloys have been used [3,4], but their elastic modulus and strength are higher than those of human bone. As a result, they invite a severe stress-shielding effect and release metallic ions, and bone density decreases with time. ...
In this study, porous magnesium (Mg) scaffolds were investigated with varying strontium (Sr) and constant zinc (Zn) concentrations through the powder metallurgy process. All samples were examined at room temperature to evaluate their microstructure, mechanical and in-vitro degradation behavior, and biological properties. Results indicated that the addition of Sr was associated with fine average grain size, increased mechanical strength, and a decreased corrosion rate. All samples show small isolated and open interconnected pores (porosities: 18-30%, pores: 127-279 µm) with a suitable surface roughness of less than 0.5 µm. All samples have mechanical properties that are hemocompatible and closer to those of natural bone. Mg-4Zn-2Sr has the highest hardness (102.61 ± 15.1 HV) and compressive strength (24.80 MPa) than Mg-4Zn-0.5Sr (85 ± 8.5 HV, 22.14 MPa) and Mg-4Zn-1Sr (97.71 ± 11.2 HV, 18.06 MPa). Immersion results revealed that samples in PBS solutions have excellent degradability properties, which makes them a promising biodegradable material for orthopaedic applications. The scaffold with the highest Sr concentration shows the best optimized mechanical and degradation behavior out of the three scaffolds, with a 2.7% hemolysis rate.
... Apart from stiffness, fast-stress-relaxation alginate gels carrying hMSCs could promote bone formation in vivo through mechanotransduction compared with those slow-stressrelaxation ones, and substantial bone regeneration is even found in the former group even without transplanted cells. [42] Mechanical deformation of the surrounding matrix was reported to affect the formation of neovascular networks in vitro and in vivo. [43] Loading of compliant fixation plates at the implantation time disrupts nascent vessel formation and vascular ingrowth, and then, impaires bone regeneration, whereas delayed loading of compliant fixation plates after 4 weeks of implantation stimulates vascular network remodeling and enhances large segmental bone regeneration. ...
To systematically unveil how substrate stiffness, a critical factor in directing cell fate through mechanotransduction, correlates with tissue regeneration, novel biodegradable and photo‐curable poly(trimethylene carbonate) fumarates (PTMCFs) for fabricating elastomeric 2D substrates and 3D bone scaffolds/nerve conduits, are presented. These substrates and structures with adjustable stiffness serve as a unique platform to evaluate how this mechanical cue affects the fate of human umbilical cord mesenchymal stem cells (hMSCs) and hard/soft tissue regeneration in rat femur bone defect and sciatic nerve transection models; whilst, decoupling from topographical and chemical cues. In addition to a positive relationship between substrate stiffness (tensile modulus: 90–990 kPa) and hMSC adhesion, spreading, and proliferation mediated through Yes‐associated protein (YAP), opposite mechanical preference is revealed in the osteogenesis and neurogenesis of hMSCs as they are significantly enhanced on the stiff and compliant substrates, respectively. In vivo tissue regeneration demonstrates the same trend: bone regeneration prefers the stiffer scaffolds; while, nerve regeneration prefers the more compliant conduits. Whole‐transcriptome analysis further shows that upregulation of Rho GTPase activity and the downstream genes in the compliant group promote nerve repair, providing critical insight into the design strategies of biomaterials for stem cell regulation and hard/soft tissue regeneration through mechanotransduction.
... As bone tissue engineering (BTE) is mainly based on the formation of tissues and bone mechanics, scaffolds, cells, and growth factors are the three main components of BTE. The useful characteristics of bones, such as their role in body structure, defense of key internal organs, facilitation of mobility, and storage of calcium and phosphate-based minerals, have increased the significance of bone tissue engineering [8,9]. Additionally, the growing importance of bone tissue engineering has been influenced by the rise in knee and hip replacement procedures over the last few years as well as the drawbacks of existing treatment options such as allografts, autografts, and ceramic and metallic implants [10]. ...
Hydroxyapatite (HA, Ca 10 (PO 4) 6 (OH) 2)-based porous scaffolds have been widely investigated in the last three decades. HA, with excellent biocompatibility and osteoconductivity, has made this material widely used in bone tissue engineering. To improve the mechano-biological properties of HA, the addition of clay to develop HA-based composite scaffolds has gained considerable interest from researchers. In this study, a cost-effective method to prepare a HA-clay composite was demonstrated via the mechanical mixing method, wherein kaolin was used because of its biocompatibility. Prawn (Fenneropenaeus indicus) exoskeleton biowaste was utilized as a raw source to synthesize pure HA using wet chemical synthesis. HA-clay composites were prepared by reinforcing HA with 10, 20, and 30 wt.% of kaolin via the mechanical mixing method. A series of characterization tools such as XRD, FTIR, Raman, and FESEM analysis confirmed the phases and characteristic structural and vibrations bonds along with the morphology of sintered bare HA, HA-kaolin clay composite, and kaolin alone, respectively. The HA-clay composite pellets, uniaxially pressed and sintered at 1100 • C for 2 h, were subjected to a compression test, and an enhancement in mechanical and physical properties, with the highest compressive strength of 35 MPa and a retained open porosity of 33%, was achieved in the HA-kaolin (20 wt.%) clay composite, in comparison with bare HA. The addition of 20% kaolin to HA enhanced its compressive strength by 33.7% and increased its open porosity by 19% when compared with bare HA. The reinforcement of HA with different amounts (10, 20, 30 wt.%) of kaolin could open up a new direction of preparing biocomposite scaffolds with enhanced mechanical properties, improved wear, and better cell proliferation in the field of bone tissue engineering.
... It is difficult to fully reproduce native bone apatite in vitro. Several types of calcium phosphate (CaP)based bone substitutes have been explored in the literature [82]. We used HA-Nc because HA is natural mineral and component of the bone, comprising about 50% of the bone weight [83], and is highly bioactive and biocompatible, and mimics well the mineral composition of bone in vertebrates. ...
Age-related musculoskeletal disorders, including osteoporosis, are frequent and associated with long lasting morbidity, in turn significantly impacting on healthcare system sustainability. There is therefore a compelling need to develop reliable preclinical models of disease and drug screening to validate novel drugs possibly on a personalized basis, without the need of in vivo assay. In the context of bone tissue, although the osteocyte network is a well-recognized therapeutic target, current in vitro preclinical models are unable to mimic its physiologically relevant and highly complex structure. To this purpose, several features are needed, including an osteomimetic extracellular matrix, dynamic perfusion, and mechanical cues (e.g., shear stress) combined with a 3D culture of osteocytes. Here we describe, for the first time, a high throughput microfluidic platform based on 96-miniaturized chips for large-scale preclinical evaluation to predict drug efficacy. We bioengineered a commercial microfluidic device that allows real-time visualization and equipped with multi-chips by the development and injection of a highly stiff bone-like 3D matrix, made of a blend of collagen-enriched natural hydrogels loaded with hydroxyapatite nanocrystals. The microchannel, filled with the ostemimetic matrix and osteocytes, is subjected to passive perfusion and shear stress. We used scanning electron microscopy for preliminary material characterization. Confocal microscopy and fluorescent microbeads were used after material injection into the microchannels to detect volume changes and the distribution of cell-sized objects within the hydrogel. The formation of a 3D dendritic network of osteocytes was monitored by measuring cell viability, evaluating phenotyping markers (connexin43, integrin alpha V/CD51, sclerostin), quantification of dendrites, and responsiveness to an anabolic drug. The platform is expected to accelerate the development of new drug aimed at modulating the survival and function of osteocytes.
... 55 Collagen-1 is a major component of natural bone and has an osteoconductive effect on bone regeneration. 56,57 Osteogenic protein expression levels of rat bone marrow mesenchymal stem cells were observed aer 21 days of osteogenic induction on scaffolds inoculated with three structures. Fig. 7 shows the expression of osteogenic proteins on DLP 3D printed HA scaffolds of BCC, FCC, and TPMS structures. ...
In the field of bone engineering, porous ceramic scaffolds are in great demand for repairing bone defects. In this study, hydroxyapatite (HA) ceramic scaffolds with three different structural configurations, including the body-centered cubic (BCC), the face-centered cubic (FCC), and the triply periodic minimal surface (TPMS), were fabricated through digital light processing (DLP) based 3D printing technologies. The effects of the structural configurations on the morphologies and mechanical properties of the DLP-based 3D printed HA scaffolds were characterized. Furthermore, in vitro evaluations, including in vitro cytocompatibility, bone alkaline phosphatase (ALP) activity assay, and protein expression, were conducted to assess HA scaffold behavior. Finally, we evaluated the effects of structural configurations from these aspects and selected the most suitable structure of HA scaffold for bone repair.
... Bone repair is a biological process consisting of the self-regeneration of the tissue that heals itself without a fibrous scar [1][2][3]. Nevertheless, bone defects with critical dimensions need to be treated with a clinical intervention [4]. Repair of bone defects is one of the challenges surgeons face in clinical practice which remains unsatisfied with traditional methods (autologous bone grafting or bone from a donor): 5% to 10% of the annual fractures fail to achieve complete repair causing harm to both the patient and the health care system [5,6]. ...
This study aims to critically analyse the workflow of the in situ bioprinting procedure, presenting a simulated neurosurgical case study, based on a real traumatic event, for collecting quantitative data in support of this innovative approach. After a traumatic event involving the head, bone fragments may have to be removed and a replacement implant placed through a highly demanding surgical procedure in terms of surgeon dexterity. A promising alternative to the current surgical technique is the use of a robotic arm to deposit the biomaterials directly onto the damaged site of the patient following a planned curved surface, which can be designed pre-operatively. Here we achieved an accurate planning-patient registration through pre-operative fiducial markers positioned around the surgical area, reconstructed starting from computed tomography images. Exploiting the availability of multiple degrees of freedom for the regeneration of complex and also overhanging parts typical of anatomical defects, in this work the robotic platform IMAGObot was used to regenerate a cranial defect on a patient-specific phantom. The in situ bioprinting process was then successfully performed showing the great potential of this innovative technology in the field of cranial surgery. In particular, the accuracy of the deposition process was quantified, as well as the duration of the whole procedure was compared to a standard surgical practice. Further investigations include a biological characterisation over time of the printed construct as well as an in vitro and in vivo analysis of the proposed approach, to better analyse the biomaterial performances in terms of osteo-integration with the native tissue.
... 113 115 HAp is an extremely suitable ceramic for constructing bones as it stimulates growth factors (e.g., bone morphogenic protein) and encourages ALP in mesenchymal stem cells. 116 The use of synthetic HAp alone in bone regeneration application is limited due to very low solubility in the body°uids and mismatch between the mechanical properties of implant and native bone tissue due to its brittle nature. 117 ...
Trauma, disease and various pathological conditions of bone may lead to the need of bone grafts and their substitutes to the affected patients. Bone grafting is a surgical process that repairs, rebuilds or replaces the lost bone. The main function of bone grafts is to induce osteoconduction, osteoinduction and osteogenesis along with providing the structural support for adherence and proliferation of bone cells at the implanted site. Bone grafts are available in a variety of substances broadly categorized into natural and synthetic grafts. The gold standard is autografts, where the bone from a person’s own body is used for implant. Other than autogenous grafts, allografts, xenografts and various isolated or polymer composites of calcium phosphate, tricalcium phosphate, calcium sulfate and hydroxyapatite are available. Zeroing in on an ideal bone graft for a specific clinical situation is a surmounting task as all grafts do not have the same properties. Hence, this review presents a deep study on the history of bone developments in the field of tissue engineering. It presents a thorough account on the natural and synthetic biodegradable electrospun polymers used for scaffolding purpose to engineer the bone.
... In compare to chemical precursors bio-based resources are economical and HAp extracted from this resources are highly preferable for removal of heavy metal ions due to its low water solubility and greater stability under redox conditions. The elemental components of HAp are hydrogen, oxygen, phosphorous and calcium along with carbon which is expected to have no toxicity 10 . Moreover, HAp isolated from biogenic resources have received considerable attention in the field of dental and bone tissue engineering because of its chemical, structural and morphological resemblance with human hard tissue minerals [11][12][13] . ...
Hydroxyapatite (HAp) is a broadly studied bioceramic for biomedical implant and bone tissue regeneration. Despite this, it is a good adsorbent of heavy metal ions. Its chemical formula is Ca10 (PO4)6(OH) 2. It was extracted by the calcination process from Ostrich bone. The obtained HAp was characterized by X-ray diffraction (XRD) and Fourier transforms infrared (FTIR) spectroscopy and was used for removal of lead (II) ion from aqueous solutions. A series of experiments were conducted in order to determine the effects of pH, contact time and sorbent dosage in a optimize condition for maximum adsorption. The results showed that the removal efficiency of Pb (II) ions reached 99.04% with an initial concentration of 50 mgL1 , pH range; 3 to7 and 1 hour contact time. The adsorption rate of Pb (II) ions onto the HAp was found incredibly fast and equilibrium was reached within 5 minute. Within this time 72.32% of lead (II) ions were removed. The equilibrium removal process of Pb (II) ions at pH range 4.5-5.5 were well described by the Langmuir isotherm model, with a maximum adsorption capacity of 430.7 mg/g. Key words: Ostrich bone, hydroxyapatite, calcinations, adsorption, Pb (II) ion, pH.
... These biomedical scaffolding requirements cannot be met by conventional single-component polymer materials and hence require a multicomponent polymer system [33]. When these polymers are made into nanocomposites, they can be used for imaging and targeting and show enormous potential in tissue engineering as they improve mechanical and functional properties and improve adhesion compared to conventional composites [34,35]. ...
Biological macromolecules like polysaccharides/proteins/glycoproteins have been widely used in the field of tissue engineering due to their ability to mimic the extracellular matrix of tissue. In addition to this, these macromolecules are found to have higher biocompatibility and no/lesser toxicity when compared to synthetic polymers. In recent years, scaffolds made up of proteins, polysaccharides, or glycoproteins have been highly used due to their tensile strength, biodegradability, and flexibility. This review is about the fabrication methods and applications of scaffolds made using various biological macromolecules, including polysaccharides like chitosan, agarose, cellulose, and dextran and proteins like soy proteins, zein proteins, etc. Biopolymer-based nanocomposite production and its application and limitations are also discussed in this review. This review also emphasizes the importance of using natural polymers rather than synthetic ones for developing scaffolds, as natural polymers have unique properties, like high biocompatibility, biodegradability, accessibility, stability, absence of toxicity, and low cost.
... The mechanical properties of PMHA composite scaffold were similar to those of cancellous bone. [20] The degradation behaviors of the composite scaffolds were investigated based on the changes in morphology and weight loss rate after being soaked in PBS solution (Figure 2e-g). The morphology and weight of the PLGA scaffold did not change significantly after 6 months of degradation. ...
The combined design of scaffold structure and multi‐biological factors is a prominent strategy to promote bone regeneration. Herein, a composite scaffold of mesoporous hydroxyapatite (HA) microspheres loaded with the bone morphogenetic protein‐2 (BMP‐2) and a poly(DL‐lactic‐co‐glycolic acid) (PLGA) matrix is constructed by 3D printing. Furthermore, the chemokine stromal cell‐derived factor‐1α (SDF‐1α) is adsorbed on a scaffold surface to achieve the sequential release of the dual‐biofactors. The results indicate that the rapid release of SDF‐1α chemokine on the scaffold surface effectively recruits bone marrow‐derived mesenchymal stem cells (BMSCs) to the target defect area, whereas the long‐term sustained release of BMP‐2 from the HA microspheres in the degradable PLGA matrix successfully triggers the osteogenic differentiation in the recruited BMSCs, significantly promoting bone regeneration and reconstruction. In addition, these structures/biofactors specially combining scaffold exhibit significantly better biological performance than that of other combined scaffolds, including the bare HA/PLGA scaffold, the scaffold loaded with SDF‐1α or BMP‐2 biofactor alone, and the scaffold with surface SDF‐1α and BMP‐2 dual‐biofactors. The utilization of mesoporous HA, the assembly method, and sequential release of the two biofactors in the 3D printed composite scaffold present a new method for future design of high‐performance bone repairing scaffolds.
... Human bone has a heterogeneous microstructure and can be considered a natural nanocomposite, due to its main composition of collagen and hydroxyapatite nanocrystals (25-50 nm) [6,8,9]. Thus, to fulfill the requirements for orthopedic application materials, bionanocomposites are a promising material for orthopedic applications as they combine biocompatible polymers and inorganic nanofillers to obtain unique structure and properties for biomedical use [10][11][12]. ...
Injection-molded nanocomposites of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) with 6 % of 3-hydroxyvalerate (HV) and amino-nanodiamonds (nD-A) were produced and characterized to investigate the effect of functionalized nanodiamonds on mechanical and biological behavior to bone replacement application. To prepare mixtures of PHBHV and nD-A in different concentrations, nD-A was dispersed in chloroform by sonication with 40 % of amplitude. Three specimens were characterized by infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (DRX), differential scanning calorimetry (DSC), 3-point flexural tests, dynamic mechanical analysis (DMA), and scanning electron microscopy (SEM). FTIR and TGA evidenced the existence of interactions between the nD-A and PHBHV. The crystallinity degree of PHBHV slightly reduced (~9 %) in nanocomposites and the morphology of the crystals changed. Nanocomposites achieved satisfactory dispersion and distribution of nD-A for low concentrations. Elastic modulus (E) increased from 1.96 ± 0.20 (PHBHV) to 2.59 ± 0.19 GPa (PHBHV/1.0%nD-A) (30 %). Despite the relatively limited dispersion, PHBHV/2.0 % nD-A had the best combination of E, strength, and maximum deformation. It had the highest glass transition temperature (43.1 vs 40.3 °C of PHBHV) and the best adhesion coefficient and reinforcement effectiveness. PHBHV-nD-A did not induce toxicity in 7 days and allowed cell fixation and expansion. These bionanocomposites should be considered for supplementary studies for bone tissue engineering.
... Bu çalışmada cam ergitme metodu kullanılarak literatürde AW cam seramik üretimi için kullanılan kompozisyon ile AW bileşenlerini içeren amorf yapıda cam ürünlerin üretimi başarılmıştır [14]. AW cam üretimi sırasında prosesin hassas bir şekilde kontrolü oldukça zor olması sebebiyle bu çalışmada monolitik olarak AW camının eldesi oldukça önemlidir. ...
... In recent years, there have been more and more research toward nanocomposites by closely mimicking the biological environment and natural matrix. Especially, the properties of nanocomposites can be modified to meet the functional requirements of each tissue, which makes it an excellent choice for tissue engineering applications [9,10]. Nanoscale scaffolds are needed to provide a suitable niche for interactions between cells and the extracellular matrix (ECM) and guide cell behaviors [11]. ...
Nanocomposites are materials that are usually created by introducing appropriate nanoparticles into a macroscopic matrix, enabling the resulting bulk nanocomposites remarkable characteristics in electrical, thermal conductivity, mechanical, optical, magnetic properties, and so on. Such nanocomposite materials are of great importance for biomedical applications, particularly promising for tissue engineering scaffolds. Recent trends in the nanocomposites field show bio-based/environmentally friendly materials to be among the components in these nanocomposite materials. Particular attention has been paid to the use of bio-based/biodegradable polymers as a matrix component in nanocomposite applications, because of their great widespread potential and advantages over other traditional synthetic materials. In this chapter, we focus on the current research trends of the tissue engineering scaffolds based on nanocomposite materials and mainly introduce the properties, types, manufacturing techniques, and tissue engineering applications of various nanocomposite biomaterials. Besides, challenges and prospects associated with nanocomposite biomaterials for the tissue engineering field were discussed. We believe that this chapter provides a new envision for building functional nanocomposite materials for broad biomedical applications.
... HA exists in the physiological environment and is an important component of the bone matrix [38]. The structure of HA is crystallographically similar to that of bone mineral, which is not only bioactive but also osteoconductive, non-toxic and non-immunogenic [39,40]. An HA coating can be prepared by various processes [41][42][43][44][45][46], among which plasma spraying is the most common technology because of its high deposition rate and low cost. ...
Dental implants have been widely applied in partially and fully edentulous patients and have shown predictable clinical outcomes, but there are still many cases of implant failures, such as osseointegration failure and peri-implant inflammation. To improve the success rate of implants, especially in improving osseointegration and antibacterial performance, various methods of implant surface modification have been applied. Surface modification methods covered include sandblasting with large-grit corundum and acid etched (SLA), plasma spraying, plasma immersion ion implantation (PIII), sputter-deposition, selective laser melting (SLM), anodic oxidation, microarc oxidation, sol-gel coating, alkaline heat treatment (AH) and Layer-by-Layer (LBL) self-assembly. This review comprehensively summarizes the influence of each method on osseointegration and biofilm attachment. The mechanical, chemical and biological disadvantages of these methods are involved. Besides, the mechanisms behind such techniques as increasing surface roughness to expand superficial area and enhance the adhesion of osteoblastic cells are discussed.
... Young's modulus is approximately GPa for native bone, and tensile and compressive strengths are approximately MPa, which are determined by the location of the bone in the body or by the specific location within the bone. Compared with cancellous bone, cortical bone exhibits much higher Young's modulus (7 -30 GPa vs. 50 -500 MPa), tensile strength (50 -150 MPa vs. 1.2 -20 MPa), compressive strength (167 -193 MPa vs. 1.9 -10 MPa), and strain to failure (1 -3% vs. 5 -7%) in the longitudinal direction [8,9] . ...
The major apparatuses used for three-dimensional (3D) bioprinting include extrusion-based, droplet-based, and laser-based bioprinting. Numerous studies have been proposed to fabricate bioactive 3D bone tissues using different bioprinting techniques. In addition to the development of bioinks and assessment of their printability for corresponding bioprinting processes, in vitro and in vivo success of the bioprinted constructs, such as their mechanical properties, cell viability, differentiation capability, immune responses, and osseointegration, have been explored. In this review, several major considerations, challenges, and potential strategies for bone bioprinting have been deliberated, including bioprinting apparatus, biomaterials, structure design of vascularized bone constructs, cell source, differentiation factors, mechanical properties and reinforcement, hypoxic environment, and dynamic culture. In addition, up-to-date progress in bone bioprinting is summarized in detail, which uncovers the immense potential of bioprinting in re-establishing the 3D dynamic microenvironment of the native bone. This review aims to assist the researchers to gain insights into the reconstruction of clinically relevant bone tissues with appropriate mechanical properties and precisely regulated biological behaviors.
... The theory of contact guidance has some of its pioneering studies at Princeton University (New Jersey-USA), where Soboyejo et al documented that linear patterned microgrooves potentially induce osseointegration, reduce scar tissue formation (Chen et al., 2007b;Levy et al., 2007;Mwenifumbo et al., 2007;Soboyejo et al., 2001aSoboyejo et al., , 2001bSoboyejo et al., , 2002 enhance bone ingrowth, and supports mechanical interlocks (Glass-Brudzinski et al., 2002;Murugan & Ramakrishna, 2005). ...
This article presents comprehensive insights and a review of cell/surface interactions on Ti-6AI-4V surfaces that are relevant to biomedical implants. The effects of surface texture are discussed for the development of biomedical implants for applications in orthopedics and dentistry. These include textured screws that have been developed along with Arginine Glycine Aspartate (RGD)-coated surfaces to enable improved osseointegration and robustness of interfaces between Ti-6Al-4V surfaces and bone cells/tissues. Following an initial review of cell-surface interactions in in-vitro studies, the results of in-vivo animal studies/human trials are presented. Measurements of adhesion and interfacial robustness are also presented before discussing their implications for the development of robust RGD-coated and textured biomedical Ti-6Al-4V surfaces.
... The abundance of free hydroxyl groups on the CNC surface can lead to various chemical modifications or the generation of novel composites with unique properties [12]. These properties and many other properties such as biocompatibility, stiffness, and high elastic modulus make the CNC proper for many applications such as drug delivery, green catalysts, polymer nanocomposite as structural reinforcement, electronics, and antimicrobial shielding [10,[13][14][15][16]. ...
Catalysts, especially heterogeneous catalysts, play an essential role in organic transformation reactions. Hence, we use a composite of cellulose nanocrystals (CNC) and Fe3O4 NPs as new support for indium(III) and evaluate the performance of fabricated Fe3O4/CNC-In(III) catalyst in the synthesis of two different heterocyclic compounds: Tetrazole and phthalazine derivatives. Although metal oxides and metal NPs are in the spotlight due to their excellent catalytic activity, they are limited in application due to their self-agglomeration in the reaction mixture, resulting in reduced performance. The addition of CNC to Fe3O4 NPs due to rich-hydroxyl sites on the CNC surface and its interaction turns Fe3O4/CNC into a stable and appropriate substrate for the immobilization of indium(III). The formation and physicochemical properties of the catalyst were endorsed by FT-IR, SEM, TEM, EDS, XRD, TGA, and elemental mapping analysis. In addition, the synthesis of substituted 2-(1H-tetrazole-5-yl) acrylonitrile and 2H-indazolo[2,1-b]phthalazinetriones was performed under solvent-free conditions; this feature is another advantage of the current procedure. Utilization of sustainable natural materials and low-cost chemicals, short reaction time, high catalytic activity, magnetic feature and easy separation with external magnet, excellent reusability without showing substantial activity loss for six runs, and uniform distribution are some of the significant advantages of this catalyst.
The schematic diagram illustrates the possible mechanism underlying the synergistic effect of polyanion and polycation on the process of mineralization which enhances the mechanical properties of assembled mineralized collagen films.
Porous Zn scaffold, as a novel biodegradable metallic material, has emerged as a promising candidate for biomedical applications. In this paper, by using carbamide particles as the pore-making agent and Zn and Mg powders as the starting materials, porous Zn-Mg alloy scaffolds were fabricated via the low-temperature sintering route. A so-called one-step hydrothermal method was applied to form a hydrophobic film on surface of the porous Zn alloy scaffolds. The degradability of the porous Zn alloy scaffolds coated with/without hydrophobic film in the simulated body fluid (SBF) was investigated, and the results show that the hydrophobic film, which can adhere well to the metal substrate with thickness around 50 μm, can effectively delay the degradation of porous Zn alloy scaffolds; the degradation rates of porous Zn alloy scaffolds coated by the hydrophobic film are 26–57% lower than those of porous scaffolds without coating; especially the degradation rate of the porous Zn-5 wt.%Mg scaffold with the coating in SBF, which is 0.32 mg/(cm2 day), is at the same level as that of pure Zn.
Nanotechnological science encompasses the development and production of newer nanomaterials. The utilization of these nanomaterials has driven substantial progress in a wide range of fields, including bioengineering and environmental science. Bio-derived nanomaterials and their composites have gained considerable interest due to their eco-friendly nature, renewable characteristics, minimized carbon footprint, and abundant presence within our ecosystem. Given these distinctive attributes of nanomaterials, certain composites can be custom-designed and refined for potential applications in tissue engineering. This chapter primarily focuses on the current trends in research in tissue engineering (TE) scaffolds crafted from biological nanomaterials. It introduces the characteristics, fabrication methods, and TE applications of various bio-based nanomaterials. Additionally, it addresses the challenges and possibilities presented by the use of these biomaterials in the field of TE. This chapter also offers a fresh perspective on creating functional bio-nanomaterials for a wide variety of biomedical applications.
In industries as diverse as automotive, aerospace, medical, energy, construction, electronics, and food, the engineering technology known as 3D printing or additive manufacturing facilitates the fabrication of rapid prototypes and the delivery of customized parts. This article explores recent advancements and emerging trends in 3D printing from a novel multidisciplinary perspective. It also provides a clear overview of the various 3D printing techniques used for producing parts and components in three dimensions. The application of these techniques in bioprinting and an up-to-date comprehensive review of their positive and negative aspects are covered, as well as the variety of materials used, with an emphasis on composites, hybrids, and smart materials. This article also provides an updated overview of 4D bioprinting technology, including biomaterial functions, bioprinting materials, and a targeted approach to various tissue engineering and regenerative medicine (TERM) applications. As a foundation for anticipated developments for TERM applications that could be useful for their successful usage in clinical settings, this article also examines present challenges and obstacles in 4D bioprinting technology. Finally, the article also outlines future regulations that will assist researchers in the manufacture of complex products and in the exploration of potential solutions to technological issues.
Bone tissue engineering involving scaffolds is recognized as the ideal approach for bone defect repair. However, scaffold materials exhibit several limitations, such as low bioactivity, less osseointegration, and poor processability, for developing bone tissue engineering. Herein, a bioactive and shape memory bone scaffold was fabricated using the biodegradable polyester copolymer's four-dimensional fused deposition modeling. The poly(ε-caprolactone) segment with a transition temperature near body temperature was selected as the molecular switch to realize the shape memory effect. Another copolymer segment, i.e., poly(propylene fumarate), was introduced for post-cross-linking and improving the regulation effect of the resulting bioadaptable scaffold on osteogenesis. To mimic the porous structures and mechanical properties of the native spongy bone, the pore size of the printed scaffold was set as ∼300 μm, and a comparable compression modulus was achieved after photo-cross-linking. Compared with the pristine poly(ε-caprolactone), the scaffold made from fumarate-functionalized copolymer considerably enhanced the adhesion and osteogenic differentiation of MC3T3-E1 cells in vitro. In vivo experiments indicated that the bioactive shape memory scaffold could quickly adapt to the defect geometry during implantation via shape change, and bone regeneration at the defect site was remarkably promoted, providing a promising strategy to treat bone defects in the clinic, substantial bone defects with irregular geometry.
Using carbamide granules as the pore-making agent, Zn-xMg alloys (x = 0 wt.%, 5 wt.%, 10 wt.%, 15 wt.%, 20 wt.%) foams with open-cell structures (porous Zn alloys) and porosity of 50 % were fabricated by means of reactive sintering powder metallurgy. The effect of Mg on the cell wall microstructures, compositions, and compression behaviors of porous Zn alloys were investigated. The results show that sintering at a temperature of 350°C can make Zn react with Mg to form intermetallics/solution, leading to effectively establishing the metallurgical bonding. When a proper Mg was added, the formed intermetallics are beneficial for improving the compression yield strength of porous Zn alloys, but too high Mg addition leads to compression strength decrease. The porous Zn-10 wt.% Mg alloy possesses the best compression property, whose compression strength is 12.4 MPa and Young’s modulus is 0.332 GPa. The fabricated porous Zn alloys possess comparable mechanical properties with those of cancellous bones, whose compression strength and Young’s modulus are 7–10 MPa and 0.259–0.332 GPa, respectively.
Biomaterials are synthetic materials used in making devices for replacing parts of a living being and to function efficiently while interacting with living tissue. Contrary to orthodox medicine in which damaged parts are amputated, the emergence of biomaterials has changed the trend. Different biomaterials including biomedical implants are being developed for different uses within the biomedi-cal field. Thus, biomedical implants are a rapidly advancing class of biomaterials that are currently used for the replacement of diseased parts or damaged tissues in the human body which may be either soft or hard tissues. These materials are developed to meet the structural and biocompatibility needs; hence, they are expected to be safe and acceptable to the human body system as the patient grows. Therefore, the age group and growth rate of the patients that need biomed-ical implants are parts of the critical factors that required adequate attention. Accordingly, this paper reviews the effects of the human age group and growth on the characteristics and responses of biomedical implants developed from bulk or nanomaterials for use in the human body system. Since, growth is a function of the age group in humans, and the three major age groups respond to growth at different rates, thus, the need to pay adequate attention to this. The review provides suitable information on the demand from each age group and provides the necessary guides on the selection of appropriate biomaterials with respect to age and growth. Hence, the need to have classifications of implants referring to; childhood implants, adolescent implants, and adult implants that focused on challenges that are common to each group.
Nowadays, biodegradable materials are considered the suitable solution for most global problems. Therefore, many types of research were made to study their properties to develop the applied methods, and introducing the concept of biodegradable polymer nanocomposites leads to the improvement of several applications like wound dressing, drug delivery, bone tissue engineering, etc. The biodegradation process generally breaks an extensive material into simpler and less complex substances, and the prefix bio refers to the reliance on vital ways. The breakdown of the material may occur through microbial enzymes, as it is one crucial biological method that analyzes polymeric materials in the environment owing to the dependence of microbes on them as a source of their nutrition. Decomposition may occur by enzymes located in the body due to their ability to catalyze the breakdown of materials. The presence of additives such as nanomaterials with the polymer affects the rate of its decomposition and the non-biotic factors present, affecting the biodegradation rate.
Strontium is a kind of element which can promote the increase of bone density and benefit the growth of bone tissue. This study combined Strontium hydroxyapatite (Sr-HAp) with magnesium oxychloride cement (MOC) to prepare a bioactive material with good osteogenic activity and degradability. The results revealed that the incorporation of 10 wt.% Sr-HAp densified the structure of MOC, slowed down the degradation rate of hydration product phase 5 in water, and enhanced the water resistance of MOC. After soaking for 28 d, the compressive strength of Sr-HAp/MOC decreased by 53%, which was lower than that of MOC (93%) and HAp/MOC (61%) without adding Sr-HAp. During the degradation process in vitro, Sr-HAp/MOC continuously released Sr2+ and the cumulative concentration of Sr2+ released in vitro after 7 d of immersion was 1.27±0.15 ppm. When Sr-HAp/MOC was soaking in simulated body fluid, Sr-HAp induced the growth and deposition of bone-like component hydroxyapatite crystals on MOC’s surface, improving MOC’s bioactivity. After implantation of femur defect in rats, the new bone tissue grew from outside to inside around Sr-HAp/MOC, which showed Sr-HAp/MOC had better osteogenic activity. MOC was containing 10 wt.% Sr-HAp can not only provide strong support for bone defects but also have the potential to promote bone regeneration.
Raman spectroscopy and Synchrotron Radiation Fourier-Transform Infrared (SR-µFTIR): Mapping have been increasingly applied as a good tool in archaeological research. The chronology of ancient samples is an essential step in archeology, and carbon dating using atomic force microscopy is the main technique. Nevertheless, the availability of instrumentation, sample preparation, and cost are barriers that limit the wide usage. The study was aimed to develop a method utilizing Raman spectroscopy and Synchrotron Radiation Fourier-Transform Infrared (SR-µFTIR) Mapping to identify ancient teeth and sort them chronologically. Furthermore, Raman spectroscopy was used to evaluate the preservation of collagen and the crystallinity of Apatite in ancient teeth. The age of fourteen ancient teeth descent from different individuals (8 from Roman period-1500BC and 4 from Byzantine period-641AD) was confirmed using carbon dating via atomic force spectrometry. The ancient teeth along with modern teeth were investigated using microRaman spectroscopy (oscillation and mapping). The typical Raman spectrum of the dentin for ancient samples was recorded and then compared to the modern teeth. The ratio of the phosphate 𝑃𝑂4 3− the band at 963 cm-1 to organic CH band at 2950 cm-1 was calculated for all samples. Raman mapping was recorded for cross-section teeth samples. The AMS data showed that the ages of the samples were 3400-3800 and 1240-1350 years for Roman and Byzantine teeth, respectively. The phosphate ν1 𝑃𝑂4 3− vibration band at (963 cm-1 ) in ancient teeth was shifted 3 cm-1 toward higher wavenumber compared to modern dentin samples (960 cm-1 ). The intensity and broadening of the carbonate apatite band at 1050 cm-1 were directly proportional to the aging. The intensity of the organic part triplet peaks at (2882, 2950, 2962) decreased with age. The ratio of phosphate band to organic C-H band was 0.346-0.388 and 0.122-0.136 for Roman and Byzantine teeth, respectively. According to the Raman mapping, the organic material in ancient teeth degraded and diffused, while in modern tooth it concentrated. Raman spectroscopy (intensity at 963 cm1 to 2950 cm-1) can be used as a qualitative tool to chronologically sort the archeological teeth samples before the use of carbon dating. The preliminary dating by Raman spectroscopy can recognize if a tooth or bone sample is archaeological or not. This step may save time and money and shall be assigned as a pre-request for AMS analysis. Raman mapping may help to explore archeological samples for best-preserved organic matter, hence identify the best candidates for further analysis (DNA extraction). In the future, the proposed method can be expanded and applied in specific cases in ancient osteology.
Phosphate glasses of various classes proven to be promising element used for diverse applications including one for clinical needs. As a bioactive glass, phosphate glass proven its potential for biomedical application. These glasses usually have certain characteristic limitations like low mechanical strength, etc. mainly by virtue of their subatomic elemental prototype structure. Earlier attempts ensured that the property of phosphate glasses can be tailor-made by incorporating suitable metal oxides of desired quantity. Accomplishment of property enhancement attempt on phosphate glasses mainly lies on the nature of element has been chosen and its quantity to be incorporated within the glass network. Amongst various metal oxides, Na2O, CaO, Ag2O, TiO2, MgO and ZnO, etc. are the few found to be suitable to get accommodation within the phosphate glass network and become a promising clinical substitute. Each metal oxide, in the choice of incorporation, has unique nature and hence results with unique characteristics after incorporating with phosphate glass. Clinical utility standards of each phosphate glass with selective additive metal oxide depends on their analytical results. Quantity of additive incorporation also significant and plays crucial role in defining its characteristics. Thus, the changes in structural, mechanical, thermal and in vitro bioactive properties of phosphate-based glasses found to be different with respect of additive incorporations.
The influences of graphene oxide (GO) and carboxyl functionalized multi-wall carbon nanotubes (f-MWCNTs) on mechanical and biological performances bone cements used as the bone substitute are investigated. The bioresorbable and bioceramics were prepared of calcium sulfate diydrate, tetra calcium phosphate and dicalcium phosphate dihydrate is fabricated by a solid-state high temperature process. Then the bioceramic is mixed with carboxymethyl cellulose, gelatin and nanocarbons. The addition of 0.5 wt% f-MWCNT and 1 wt% GO is found to increase the compressive strength of the resultant nanocomposite by %50 and %55, respectively, in comparison to that of the bare bone cement. 1 wt% GO incorporated bone substitutes had the optimum mechanical properties which had compressive modulus and compressive strength of 1.9 ± 0.3 and 35.8 ± 0.5 MPa, respectively. Moreover, GO is found to be more effective than f-MWCNT in stabilizing pH. The degradation rate of the bone cement is stabilized through GO incorporation but increased by incorporating f-MWCNT. Bone substitutes up to 1 wt% nanocarbons exhibit biocompatibility and MC3T3-E1 pre-osteoblasts were mineralized after 14 days of cell culture. The results demonstrate that the physicochemical properties of the nanocomposites are significantly affected by the concentration and surface properties of nanocarbons.
The biodegradable nanocomposite of poly(methacrylated pyromellitylimidoalanine) (PM(PMA-ala)) and hydroxyapatite (HAp) was prepared by dispersing nanosized needle-like HAp particles prepared by homogeneous precipitation under hydrothermal condition into the crosslinked PM(PMA-ala) network via in-situ photo-polymerization. The conversion of carbon carbon double bonds of multifunctional anhydride monomers after the heat treatment can be over 90%, and the HAp needles are distributed homogeneously in the PM(PMA-ala) crosslinking network. By increasing the content of HAp, the mechanical properties of HAp/PM(PMA-ala) nanocomposite is improved two to three times those of PM(PMA-ala) itself. Furthermore, in contrast with PM(PMA-ala), the nanocomposite HAp/PM(PMA-ala) has higher modulus retention and lower mass loss at the same degradation time, and this tendency will be enhanced as the increase of the content of HAp.
This paper reviews the past, present, and future of the hydroxyapatite (HAp)-based biomaterials from the point of view of preparation of hard tissue replacement implants. Properties of the hard tissues are also described. The mechanical reliability of the pure HAp ceramics is low, therefore it cannot be used as artificial teeth or bones. For these reasons, various HAp-based composites have been fabricated, but only the HAp-coated titanium alloys have found wide application. Among the others, the microstructurally controlled HAp ceramics such as fibers/whiskers-reinforced HAp, fibrous HAp-reinforced polymers, or biomimetically fabricated HAp/collagen composites seem to be the most suitable ceramic materials for the future hard tissue replacement implants.(Received February 03 1997)(Accepted July 25 1997)
Bone marrow stromal cells are progenitors of skeletal tissue components such as bone, cartilage, the hematopoiesis-supporting stroma, and adipocytes. In addition, they may be experimentally induced to undergo unorthodox differentiation, possibly forming neural and myogenic cells. As such, they represent an important paradigm of post-natal nonhematopoietic stem cells, and an easy source for potential therapeutic use. Along with an overview of the basics of their biology, we discuss here their potential nature as components of the vascular wall, and the prospects for their use in local and systemic transplantation and gene therapy.
Completely densified hydroxyapatite ceramics were successfully sintered in a 500 W microwave oven within 5 - 10 min at sintering temperature of 1100 - 1300 deg C. Compared with the hydroxyapatite ceramics sintered by the conventional method, the microwave sintered hydroxyapatite ceramics have the following characteristics: denser microstructure and finer grain size, as well as the improved mechanical strength, and the process consumes a small fraction of the energy and time of conventional sintering.
Glutaraldehyde was used as a crosslinkage agent for the preparation of porous hydroxyapatite/collagen nanocomposites. Hydroxyapatites (HAp) are the suitable bone subsitutes that gives biocompatible, bioactive, biodegradable and osteoconductive properties of natural bone. The microstructures of the composites were observed by scanning electron microscopy and the chemical reaction between HAp nanocrstals and functional groups of collagen was evaluated using diffuse reflection method. The self-alignment of collagen bundles occured during natural drying and HAp crystals with collegen fiber were intensified by glutaraldehyde.
Xenogeneic bone procured from the slaughterhouse waste was deproteinated by heat treatment method intended for use as a bone
substitute. The effect of heat treatment was investigated by thermal analysis and by physico-chemical methods such as X-ray
powder diffraction (XRD) and Fourier transformed infrared (FTIR) spectroscopy. The heat treatment temperatures for the bovine
bone samples were predetermined by thermogravimetric (TG) analysis. The XRD results revealed that the process of heat treatment
promoted the crystallinity of bone samples, particularly at 700 and 900†C. There was no secondary phase transformation detected
for heat- deproteinated bone except the presence of the hydroxyapatite (HA) phase, which indicated its phase purity even at
a higher temperature. The FTIR spectra of raw bone and bone heated at 300†C indicated the presence of organic macromolecules
whereas these disappeared in the samples heated at 500, 700 and 900†C, which suggested the removal of antigenic organic matters
around 500†C. The same results were also confirmed quantitatively by calculating the amount of collagen using hydroxyproline
estimation. There was no significant change in the TG-thermogram of bone heated at 500, 700 and 900†C, which indicated their
thermal stability. These findings implied that the heat treated bone at 500†C had properties similar to carbonated HA with
low crystallinity, while 700 and 900†C samples had the same with higher crystallinity. As low temperature treatment does not
alter morphological and structural properties, we propose that the 500†C heat treated xenogeneic bone may act as an excellent
osteogenic bone substitute.
Hydroxyapatite (Ca10(PO4)6(OH)2:HA) with highly designed microstructures is required for bone filling materials and tissue engineering of cultured bones. This study deals with the shape control of HA particles and preparation of HA sheet from fibrous HA. Fibrous particles of HA with the aspect ratio of about 60 were prepared hydrothermally at 150 °C from the mixed solution of calcium acetate and phosphoric acid. The aspect ratio of the fibrous particles depended on the concentration and the value of Ca/P ratio of the mixed solution. The HA sheet must be a biostable material according to the soaking test with simulated body fluid.
Electrospinning is a process by which high voltages are used to produce an interconnected membrane-like web of small fibers (10–500 nm in diameter). This novel fiber spinning technique provides the capacity to lace together a variety of types of polymers, fibers, and particles to produce ultrathin layers. Of particular interest are electrospun membranes composed of elastomeric fibers, which are under development for several protective clothing applications. The various factors influencing electrospun nonwoven fibrous membrane structure and transport properties are discussed. Performance measurements on experimental electrospun fiber mats compare favorably with transport properties of textiles and membranes currently used in protective clothing systems. Electrospun layers present minimal impedance to moisture vapor diffusion required for evaporative cooling. There may be special considerations in the application of elastomeric membranes for protective clothing. Effects of membrane distortion upon transport behavior of the structure might be significant. Preliminary measurements have found that changes in elastomeric membrane structure under different states of biaxial strain were reflected in measurements of air flow through the membrane. Changes in membrane structure are also evident in environmental scanning electron microscope (SEM) images of the pore/fiber rearrangement as the membrane is stretched. Experimental measurements and theoretical calculations show electrospun fiber mats to be extremely efficient at trapping airborne particles. The high filtration efficiency is a direct result of the submicron-size fibers generated by the electrospinning process. Electrospun nanofiber coatings were applied directly to an open cell polyurethane foam. The air flow resistance and aerosol filtration properties correlate with the electrospun coating add-on weight. Particle penetration through the foam layer, which is normally very high, was eliminated by extremely thin layers of electrospun nanofibers sprayed on to the surface of the foam. Electrospun fiber coatings produce an exceptionally lightweight multifunctional membrane for protective clothing applications, which exhibits high breathability, elasticity, and filtration efficiency.
This is a comprehensive and accessible overview of what is known about the structure and mechanics of bone, bones, and teeth. In it, John Currey incorporates critical new concepts and findings from the two decades of research since the publication of his highly regarded The Mechanical Adaptations of Bones. Crucially, Currey shows how bone structure and bone's mechanical properties are intimately bound up with each other and how the mechanical properties of the material interact with the structure of whole bones to produce an adapted structure. For bone tissue, the book discusses stiffness, strength, viscoelasticity, fatigue, and fracture mechanics properties. For whole bones, subjects dealt with include buckling, the optimum hollowness of long bones, impact fracture, and properties of cancellous bone. The effects of mineralization on stiffness and toughness and the role of microcracking in the fracture process receive particular attention. As a zoologist, Currey views bone and bones as solutions to the design problems that vertebrates have faced during their evolution and throughout the book considers what bones have been adapted to do. He covers the full range of bones and bony tissues, as well as dentin and enamel, and uses both human and non-human examples. Copiously illustrated, engagingly written, and assuming little in the way of prior knowledge or mathematical background, Bones is both an ideal introduction to the field and also a reference sure to be frequently consulted by practicing researchers.
This paper reviews the current understanding of adhesion between a synthetic polymer and a second material. The second material may be inorganic, such as glass, or it may be another polymer but is assumed to be smooth. No attempt is made to be definitive; rather the aim is to give a broad picture of the issues and understanding that the author considers to be important. The adhesion of pressure sensitive adhesives is considered separately from that of more rigid polymers as Van der Waals forces alone can cause significant adhesion only with the former materials. Attempt is made to distinguish between two important issues, the method by which the materials interact at a molecular or polymer chain level and the crack tip deformation process that occur within the polymer. It is these deformation processes that dissipate the energy described by the interface toughness. A tough adhesive bond requires sufficient interface coupling to induce considerable deformation close to the interface within the bulk material.
A nano-hydroxyapatite/collagen composite was prepared by precipitation of hydroxyapatite from an aqueous solution onto collagen. Mouse peritoneal macrophages were used to investigate the in vitro biodegradation of the composite. The results showed the mechanism of phagocytosis and extracellular degradation process. The cells that belong to the mononuclear phagocyte system showed some morphological characteristics similar to those of osteoclasts and made pits on the composite surface. The local modification of the material surface by the cell was another phenomenon distinguishable from the degradation process. The degradation and modification made the material porous with s widely varying Ca/P ratio.
Hydroxyapatite reinforced polyethylene composites of 0. 3, 0. 4 and 0. 5 volume fraction were machined and implanted into the lateral condyles of New Zealand White Rabbits. The response of the surrounding tissue was assessed using histology and electron microscopy techniques for periods up to 6 months. Preliminary data is also presented from push-out tests showing the level of the interfacial shear strength of the implant/bone interface.
A suitable method was developed to enhance the use of coralline hydroxyapatite (CHA) as carrier in drug delivery systems. CHA was surface modified by grafting with glycidylmethacrylate using redox initiators. FT-IR spectroscopy and X-ray diffraction were employed for the proof of grafting and phase purity of the graft copolymer. An antibiotic agent, gentamicin, was incorporated into unmodified CHA (UCHA) and surface modified CHA (SCHA). The percentage of loading and release profiles of gentamicin for UCHA and SCHA were evaluated and compared. It was found that the SCHA exhibited higher loading efficiency for gentamicin than the UCHA. In-vitro release profile of gentamicin was assayed by elution in phosphate buffered saline of pH 7.4 at 37°C. The in-vitro release of gentamicin from SCHA occurred up to 12 days, w hereas it was 9 days for UCHA, for the release of most of the gentamicin incorporated. This prolonged release of gentamicin from SCHA was attributed to more interaction between the amino groups of gentamicin and epoxy groups. The results suggest that the SCHA coupled with gentamicin could serve as an effective method of administrating local chemotherapy primarily when used as a strut graft for bone defects.
Chemically and thermally treated bovine bone has been proposed as an alternative to bone grafts and synthetic bone substitutes. Fluorinated bovine hydroxyapatite (FBHA) was prepared by two different methods at low and high temperatures. The effect of reaction temperature and fluorine concentration on the crystal morphology, phase purity and functional groups were observed by X-ray diffraction (XRD) method and FT-IR spectroscopy. The XRD results indicted that [3 0 0] reflection peak was shifted towards higher angle due to fluorination. The a-axis dimensions of both the FBHA samples were found to be decreased with the fluorination. The FT-IR spectra of FBHA samples confirm partial fluorination into the hydroxyl group of bovine hydroxyapatite. The in vitro physiological stability study was performed in phosphate buffered saline (PBS) of pH 7.4 at 37 °C and the samples were found to be quite stable for about a month. These results suggest the tremendous potential of fluorinated bovine hydroxyapatite as a bone substitute due to their bioactive nature.
The aim of the present clinical study was to test whether or not the addition of recombinant human bone morphogenetic protein-2 (rhBMP-2) to a xenogenic bone substitute mineral (Bio-Oss®) will improve guided bone regeneration therapy regarding bone volume, density and maturation. In 11 partially edentulous patients, 34 Brånemark implants were placed at two different sites in the same jaw (five maxillae, six mandibles) requiring lateral ridge augmentation. The bone defects were randomly assigned to test and control treatments: the test and the control defects were both augmented with the xenogenic bone substitute and a resorbable collagen membrane (Bio-Gide®). At the test sites, the xenogenic bone substitute mineral was coated with rhBMP-2 in a lyophilization process. Following implant insertion (baseline), the peri-implant bone defect height was measured from the implant shoulder to the first implant–bone contact. After an average healing period of 6 months (SD 0.17, range 5.7–6.2), the residual defects were again measured and trephine burs were used to take 22 bone biopsies from the augmented regions. The healing period was uneventful except for one implant site that showed a wound dehiscence, which spontaneously closed after 4 weeks. Later at reentry, all implants were stable. At baseline, the mean defect height was 7.0 mm (SD 2.67, range 3–12 mm) at test and 5.8 mm (SD 1.81, range 3–8 mm) at control sites. At reentry, the mean defect height decreased to 0.2 mm (SD 0.35, range 0–1 mm) at test sites (corresponding to 96% vertical defect fill) and to 0.4 mm (SD 0.66, range 0–2 mm) at the control site (vertical defect fill of 91%). Reduction in defect height from baseline to reentry for both test and control sites was statistically significant (Wilcoxon Pt-test Pt-test PTo cite this article:Jung RE, Glauser R, Schärer P, Hämmerle CHF, Sailer HF, Weber FE. Effect of rhBMP-2 on guided bone regeneration in humans. A randomized, controlled clinical and histomorphometric study. Clin. Oral Impl. Res, 14, 2003; 556–568
An attempt was made to enhance the bioresorbability of hydroxyapatite (HA) by controlling its particle size to nano/submicron level. A wet chemical method was employed for the synthesis of HA nanocrystals at low temperature in an aqueous medium having the ability of bioresorbtion in stimulated body fluid. The prepared free flowing nano HA was characterized for its phase purity, chemical homogeneity and functionality. The obtained results indicated that it has nanoscale morphological structure with mean particle size of 220nm in diameter. Further, its ionic dissolution rate was found to be quite higher than conventional HA and closer to biological apatite owing to its nanostructure processing. Accordingly, it suggests that the nano-HA has superior bioresorbtion and close chemical and crystallographic structure with natural bone apatite.
Hydroxyapatite nanofibers were prepared by a simple route at ambient conditions, by which the reaction of calcium chloride and sodium phosphate took place. The length and diameter were 160–220 and 5 nm, respectively. The microstructure of the resultant nanofibers was studied by means of X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transmission infrared spectrometer (FTIR) and Raman spectra. It has been found that hydroxyapatite nanofibers have high crystalline and fairly pure phase.
Osteoblast cells were separated from the neonatal rat calvaria and co-cultured on a novel mineralized hydroxyapatite/collagen/poly(lactic acid) composite scaffold. By using this static cell culture, a three-dimensional osteoblasts/composite bone-like was constructed in vitro. The culture process was observed by scanning electron microscopy, fluorescence microscopy, confocal laser scanning microscopy, and histological analysis. Cells were observed to spread and proliferate throughout the inner-pores of the scaffold material. After a 12-day culture, the cells had grown into the interior scaffold about 200–400 μm depth of the composite by histological section observation. This mobile behavior of osteoblasts appeared to be similar to the composition and hierarchical structure of bone tissue. The adherence and migration of osteoblast cells in this three-dimensional composite is clinically important for large bone defect repair based on tissue engineering.
With the current widespread application of surgical implants, consideration of the effects of the human environment on the implantable materials and of the influence of the materials on the human cells and tissues has become essential. When implanted in the body, all implantable materials undergo chemical or electrochemical dissolution at some finite rate which may alter appreciably with time. Also, the human environment imposes mechanical forces upon surgical implants, usually of low magnitude and high frequency of application. In this review, the tendency of implantable materials to undergo mechanical, chemical, electrochemical, and mechanicochemical failure is described. The results of available accelerated laboratory tests on specimens studied under conditions that simulate those in the human body are compared with observations on implants after their removal from humans and experimental animals. The potentially deleterious side-effects of implant dissolution on adjacent and distant tissues such as tissue toxicity, hypersensitivity, altered resistance to infection, hypercoagulation of the blood, and malignant transformation are described. Also, the effects of mechanical forces imposed by implants on adjacent tissues are discussed. Finally, the primary goals for future research on implantable materials and surgical implants are outlined.
A designed hierarchical structure was made by self-assembly of nano-fibrils of mineralized collagen resembling extracellular matrix. The collagen fibrils were formed by self-assembly of collagen triple helices. Hydroxyapatite (HA) crystals grew on the surface of these fibrils in such a way that their c-axes were oriented along the longitudinal axes of the fibrils. The mineralized collagen fibrils aligned parallel to each other to form mineralized collagen fibers. For the first time, the new hierarchical self-assembly structure of collagen−hydroxyapatite composite was verified by conventional and high-resolution transmission electron microscopy.
Hydroxyapatite lathlike monocrystalline particles were prepared using high-energy dispersing equipment in combination with a pH shock-wave method. The Ca/P atomic ratios were very close to theoretical, and the acidic group content was very small. The particles were nonporous, with anisotropic crystal growth and average grain size ∼140–1300 nm in length, ∼20–100 nm in width, and ∼10–40 nm in thickness. The high-speed dispersing equipment created the proper hydrodynamic conditions for lathlike particle growth in the [001] direction. The hydroxyapatite particles formed aggregates of 1–5 μm average diameter.
The nucleation of hydroxyapatite (HAp) crystal through chemical interaction with collagen was investigated. A collagen membrane was soaked in a supersaturated simulated body fluid (1.5 SBF) solution with ion concentrations at 1.5 times that of normal simulated body fluid (1.0 SBF). A few carbonate-containing HAp crystals were formed mostly on the edge-side of the collagen membrane after 4 weeks. In the Fourier-transform infrared spectometry (FTIR) results, the carboxylate band of the collagen membrane showed red chemical shifts after the formation of HAp crystals, which coincided well with the decrease of the calculated bond orders of the carboxylate group when chelated with a calcium ion, which emulated the first-step nucleation of HAp crystal on the carboxylate group of collagen. The result implies that the binding of a calcium ion to the carboxylate group of collagen is one of the key factors for the nucleation of HAp crystals in a 1.5 SBF solution.
A novel method for preparing calcium hydroxyapatite (Ca10(PO4)6(OH)2: HAp) fibers has been developed. HAp fibers can be prepared successfully by heating a compact consisting of calcium metaphosphate (ß-Ca(PO3)2) fibers with Ca(OH)2 particles in air at 1000°C and subsequently treating the resultant compact with dilute aqueous HCl solution. The ß-Ca(PO3)2 fibers and the Ca(OH)2 in the compact were converted into fibrous HAp and CaO phases by the heating, and the CaO phase was removed by acid-leaching. HAp fibers obtained in the present work were 40-150 µm in length and 2-10 µm in diameter. The fibers had almost the same dimensions as those of the ß-Ca(PO3)2 fibers.
The coating of a carbonate-containing hydroxyapatite (HAp) on a nonbioactive collagen membrane via a biomimetic method has been investigated. The collagen membranes were soaked in a simulated body fluid (SBF) solution with and without citric acid, and carbonate-containing HAp formed only in the SBF solution that contained citric acid. The results were explained in terms of the strong chelation ability of citric acid with the calcium ion. Practical application may involve the inclusion of citric acid in the SBF solution to promote the formation of HAp on previously nonbioactive collagen membranes.
A hydroxyapatite/collagen/chondroitin sulfate nanocomposite that partly mimicked the composition of cartilage was synthesized through a novel precipitation method, using a calcium hydroxide suspension and phosphoric acid solutions that contained several mixing ratios of type II collagen (Col) and chondroitin sulfate (ChS). The precipitates were shaped and consolidated via filter pressing and subsequent cold isostatic pressing, respectively. A preferential alignment of the crystallographic c-axis of the hydroxyapatite nanocrystals along the longitudinal direction of the Col and ChS mixture was observed. The fracture strength and Vickers hardness of the nanocomposites were in the ranges of 35–50 and 119–219 MPa, respectively. This nanocomposite may be applicable for use as a bone substitute, because of its potential capability of bone remodeling through endochondral ossification.
Well-dispersed sol with crystalline hydroxyapatite (HAp) was obtained directly by milling a mixture comprising Ca(OH)2, an aqueous solution of H3PO4 and a dispersant, an ammonium salt of polyacrylic acid. The average crystallite size of HAp was below 20 nm. Ca/P molar ratio of the product was 1.51 0.04, i.e. Ca deficient from stoichiometric HAp. Minimum apparent viscosity was attained at a dispersant concentration 0.92wt% of sol. An as-milled sol was diluted by a factor 10–2.61 solid wt% to give a Newtonian fluid of 2 mPa s. From the diluted sol, we obtained a few m thick dense film of HAp by dip coating on the slide glass precoated by chitosan.
In the presence of fine silk cocoon (silk fibroin, SF) powder, a low viscosity sol of nano-hydroxyapatite (HAp, Ca10(PO4)6(OH)2)—SF was synthesized by a wet mechanochemical reaction. Nano crystals of HAp are oriented along their c-axis. The secondary structure of SF was changed by milling. A uniform thin gel film was obtained by a simple dip coating on the glass substrate precoated by chitosan.
One of the most important objectives in biomaterials science is the development of new materials for bone substitution. It has been found that hydroxyapatite (HAp), which is the most widely studied bioceramic, has an excellent biocompatibility and a certain degree of bioactivity [1, 2]. However, HAp is limited in its use because it is brittle compared with natural bone. In order to improve the toughness and bioactivity of bone substitution materials, biocomposites made of HAp and biocompatible organic components or bioactive glass have been developed in recent years [3-10]. Among these materials, HAp/collagen composite is of special interest because it mimics the composition of natural bone [7-10]. Preliminary study reveals that this composite has a better osteo-inductive capacity in cell culture than monolithic HAp [9]. So far, HAp/collagen composite is still at the initial stage of development. It is well known that HAp is nanometre sized and deposits in an orderly way on the collagen matrix in natural bone. However, with the synthetic methods reported, it is not easy to obtain either a uniformly mixed composite [7], or a fine crystal sized material [8-10], while these two factors are important to the bioactivity of the composite [2]. Therefore, new methods are needed to obtain an HAp/collagen composite which mimics not only the composition but also the microstructure of natural bone. This letter reports a new preparation method of HAp/ collagen composite in which nanometre sized HAp is homogeneously dispersed in collagen matrix. The results of biological testing will be published separately. Commercially purchased HAp powder and type 1 insoluble collagen from bovine achilles tendon were used as starting materials. Firstly, i g HAp was dissolved in 150 ml, 0.1 N HC1 at 20 °C and 450 mg type i collagen was added to the solution, which was then ultra-sonicated, using a Model Gl125 ultrasonator, until a thoroughly mixed slurry was obtained. Secondly, this solution was diluted to 2000 ml with distilled water, and 23.376 g NaC1 was added to increase the stability of the calcium containing solution [11]. This resulted in a 5 mM calcium solution with pH 3.0. At the third step, the solution was gently stirred at 20 °C, and 0.05 M potassium hydroxide solution was added in drops to the calcium solution to adjust the pH to 7.4. When the pH exceeded about 7.0, the solution became supersaturated and HAp started to precipitate onto the collagen. The solution was maintained at pH 7.4 for 10 min, after which the composite was harvested by centrifugation at 5000 rpm and freeze-dried. The
A new process is described for preparing dense, polycrystalline hydroxylapatite. This material has close to theoretical density
and is free of fine pores and second phases. The best material has an average compressive strength of 917 MN m−2 (133×103 psi), and polished samples have an average tensile strength of 196 MN m−2 (28.4×103 psi). The material is highly translucent, and the degree of translucence depends upon processing conditions. The relationship
between processing variables and microstructure, strength, and translucence is described. This dense hydroxylapatite has good
promise for bone implants and dental applications.
Combinations of hydroxyapatite (HAP) and bone morphogenetic protein (BMP) are anticipated to provide potent alternatives
to autogenous bone grafts. In this study, porous HAP rods were treated with 1 μg or 5 μg of rhBMP-2 subperiosteally implanted
on the cranial bone of rabbits. The HAP rods were then removed 3, 6, or 9 weeks after implantation and subjected to physical
strength determinations. Even the control group, without addition of rhBMP-2 to the rods, demonstrated significantly increased
three-point bending strength at 9 weeks compared with that before implantation. Groups receiving rhBMP-2-treated rods showed
significant increases in strength beginning at 3 weeks. In histological examination, a slight degree of bone formation was
seen around the HAP rods in the control group; however, clearly visible bone formation was found penetrating the rod pores
of the rhBMP-2 groups. Histological examination also revealed that bone formation was inclined to be greater at the higher
dose, 5 μg, of rhBMP-2. Results indicated that rhBMP-2, even in a small dose, increases the strength of porous HAP, which
is basically a ceramic and thus has the characteristic disadvantage of being fragile, at a relatively early stage following
implantation as the result of bone ingrowth to the pores of HAP.
To fabricate an artificial bone material having bone-like nanostructure and chemical composition, a composite composed of hydroxyapatite (HAp) and collagen was synthesized under a biomimetic condition through the self-organization mechanism between HAp and collagen. The hydroxyapatite/collagen (HAp/Col) composite prepared demonstrated bone-like orientation that the c-axes of HAp nanocrystals were regularly aligned along collagen fibrils. Considering crystallography, driving force of the self-organization of HAp and collagen was assumed to be an interaction between their surfaces, i.e., Ca2+ ions on the HAp crystals and dissociated carboxyl residues on the collagen molecules. Biocompatibility of the HAp/Col composite was similar to or better than that of HAp ceramics that are known to have an excellent biocompatibility. Bone tissue reactions of the composite demonstrated osteoclastic resorption of the composite followed by new bone formation by osteoblasts, which is very similar to the reaction of a transplanted autogenous-bone. From these results, we conclude that the HAp/Col composite can be successfully utilized as an artificial bone material in both the medical and dental fields as an in vivo filler and in vitro tissue regenerator.
Select functions of osteoblasts (bone-forming cells) on nanophase (materials with grain sizes less than 100 nm) alumina, titania, and hydroxyapatite (HA) were investigated using in vitro cellular models. Compared to conventional ceramics, surface occupancy of osteoblast colonies was significantly less on all nanophase ceramics tested in the present study after 4 and 6 days of culture. Osteoblast proliferation was significantly greater on nanophase alumina, titania, and HA than on conventional formulations of the same ceramic after 3 and 5 days. More importantly, compared to conventional ceramics, synthesis of alkaline phosphatase and deposition of calcium-containing mineral was significantly greater by osteoblasts cultured on nanophase than on conventional ceramics after 21 and 28 days. The results of the present study provided the first evidence of enhanced long-term (on the order of days to weeks) functions of osteoblasts cultured on nanophase ceramics; in this manner, nanophase ceramics clearly represent a unique and promising class of orthopaedic/dental implant formulations with improved osseointegrative properties.
Osteoblast adhesion on nanophase alumina (Al2O3) and titania (TiO2) was investigated in vitro. Osteoblast adhesion to nanophase alumina and titania in the absence of serum from Dulbecco’s modified Eagle medium (DMEM) was significantly (P<0.01) less than osteoblast adhesion to alumina and titania in the presence of serum. In the presence of 10% fetal bovine serum in DMEM osteoblast adhesion on nanophase alumina (23 nm grain size) and titania (32 nm grain size) was significantly (P<0.05) greater than on conventional alumina (177 nm grain size) and titania (2.12 μm grain size), respectively, after 1, 2, and 4 h. Further investigation of the dependence of osteoblast adhesion on alumina and titania grain size indicated the presence of a critical grain size for osteoblast adhesion between 49 and 67 nm for alumina and 32 and 56 nm for titania. The present study provides evidence of the ability of nanophase alumina and titania to simulate material characteristics (such as surface grain size) of physiological bone that enhance protein interactions (such as adsorption, configuration, bioactivity, etc.) and subsequent osteoblast adhesion.
In this paper the semi-interpenetrating network (semi-IPN) technique was used for the first time to prepare bone implant composites containing hydroxyapatite (HAP) nanocrystals. The prepared nanocomposites are expected to combine several property advantages including good mechanical strength, modified degradation rate and excellent osteoconductivity. The semi-IPN matrix based on the linear poly (ε-caprolactone) (l-PCL) and the network poly (ε-caprolactone) (net-PCL) structures are revealed to be phase separation structures. The morphology of net-PCL is featured by intracrosslinked microdomains (1–10 μm) that further interconnect with each other to form the network over the whole sample. The net-PCL component is totally amorphous at room temperature for the nanocomposites containing HAP up to 12.3 wt%. Further, the crystallinity of l-PCL is greatly decreased due to the presence of net-PCL as compared with that for pure l-PCL. The incorporation of l-PCL into the net-PCL network could significantly improve the mechanical properties of pure net-PCL. A great improvement in mechanical properties is observed for the nanocomposites if the HAP content is increased to 15.8 wt%. This transition is in agreement with that the net-PCL component changes from amorphous state to crystalline state at this composition.
Calcium phosphate (CaP) compounds are becoming of increasingly great importance in the fiel of biomaterials and, in particular, as bone substitutes. Recent discoveries have accelerated this process, but have simultaneously rendered the field more complicated for the everyday user. Subtle differences in composition and structure of CaP compounds may have a profound effect on their in vivo behaviour. Therefore, the main goal of this article is to provide a simple, but comprehensive presentation of CaP compounds. Reference is made to the most important commercial products.
An overview of various biomedical applications of polymer-composite materials reported in the literature over the last 30 years is presented in this paper. For the benefit of the readers, general information regarding structure and function of tissues, types and purpose of implants/medical devices, and various other materials used, are also briefly presented. Different types of polymer composite that are already in use or are investigated for various biomedical applications are presented. Specific advantages of using polymer-composite biomaterials in selected applications are also highlighted. The paper also examines the critical issues and scientific challenges that require further research and development of polymer composite materials for their increased acceptance in the biomedical industry.
Calcium phosphate ceramics, β-calcium pyrophosphate (Ca2P2O7), β-tricalcium phosphate (Ca3(PO4)2), hydroxyapatite (Ca10(PO4)6(OH)2) and tetracalcium phosphate (Ca4(PO4)2O), were prepared. The calcium:phosphorus ratios and microporosities were 1 (31.6%), 1.5 (1.6%), 1.66 (1%) and 2 (34.6%) respectively. Samples (15 mm × 10 mm × 2 mm), abraded with No. 2000 alumina powder, were implanted into the tibial metaphysis of mature male rabbits. Failure load, when an implant detached from the bone or the bone itself broke, was measured. At 10 wk after implantation, the failure loads in β-calcium pyrophosphate, β-tricalcium phosphate, hydroxyapatite and tetracalcium phosphate were 31.65 ± 9.90 N, 72.81 ± 19.01 N, 49.49 ± 17.25 N and 43.22 ± 14.99 N respectively. At 25 wk after implantation, the values were 47.04 ± 14.90 N, 71.34 ± 19.50 N, 69.09 ± 16.17 N and 62.03 ± 18.62 N respectively. Histologically, bone bonding behaviour of calcium phosphate ceramics did not vary with the calcium:phosphorus ratio, as observed by contact microradiogram, Giemsa surface staining and scanning electron micrograph-electron probe micro analysis. There was no intervening soft tissue at the interface of bone and ceramics. Hydroxyapatite or tricalcium phosphate are used as bone substitutes. However, their mechanical strength is insufficient for weight-bearing and they are used as bone filler. This study showed that the apparent insignificance of strict calcium:phosphorus ratio with respect to the biological results greatly simplifies processing of calcium phosphate ceramics for clinical application. In clinical application, calcium phosphate ceramics with different Ca:P can be used as bone fillers for bone defects or bone cavities under non-weight-bearing conditions.
A nano-composite of bone-like apatite/collagen was prepared by a new method—low-temperature in situ synthesis using calcium nitrate, diammoniun hydrogen phosphate and cow hide collagen as starting materials. The composite was investigated via X-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It was found that bone-like nanoapatite particles were distributed uniformly in collagen fibrils in the composite. The composite with homogeneous microstructure was similar to natural bone in crystallite phase composition and crystal size. The biomimetic composite is expected to exhibit desirable properties in biomedical applications.
Bone defects are generally filled using autologous implants because artificial bone materials have low bioaffinity. However, natural bone can induce infections and antigenic reaction, therefore, the preparation of artificial material with composition, structure and biological feature comparable to those of bone is a goal to be pursued. The aim of this work was to follow a biologically inspired approach performing a direct nucleation of hydroxyapatite (HA) on self-assembled collagen fibers to set up a collagen–hydroxyapatite nanocrystals composite as a new particularly attractive material for bone repair and reconstruction. X-ray diffractometric technique, thermogravimetric (TG–DTG), spectroscopic (FT-IR, ICP), microscopic (SEM, TEM) analyses have been used to highlight the likeness of the artificial biomimetic HA/Col composite with natural bone tissue.