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Scaffolds in Tissue Engineering Bone and Cartilage
Abstract
Musculoskeletal tissue, bone and cartilage are under extensive investigation in tissue engineering research. A number of biodegradable and bioresorbable materials, as well as scaffold designs, have been experimentally and/or clinically studied. Ideally, a scaffold should have the following characteristics: (i) three-dimensional and highly porous with an interconnected pore network for cell growth and flow transport of nutrients and metabolic waste; (ii) biocompatible and bioresorbable with a controllable degradation and resorption rate to match cell/tissue growth in vitro and/or in vivo; (iii) suitable surface chemistry for cell attachment, proliferation, and differentiation and (iv) mechanical properties to match those of the tissues at the site of implantation. This paper reviews research on the tissue engineering of bone and cartilage from the polymeric scaffold point of view.
... Three-dimensional printing was developed in the early nineties at the Massachusetts Institute of Technology by Sachs and his collaborators. It is a technique that applies inkjet printing of a binder in the process of handling powdered materials [132,133]. ...
... A key advantage of this technique is the absence of organic solvents, but drawbacks include the inability to incorporate growth factors, high operating temperatures, and a limited range of applicable polymers. The benefits of using this technique for scaffold preparation are high porosity with no usage of toxic solvents, good mechanical strength and flexibility of processing and material handling; however, its applicability to biodegradable polymers excludes a few, like PCL and PLA [104,133]. The fusion and deposition modelling technique, represented in Figure 5, involves adding molten material in extremely thin layers. ...
... A key advantage of this technique is the absence of organic solvents, but drawbacks include the inability to incorporate growth factors, high operating temperatures, and a limited range of applicable polymers. The benefits of using this technique for scaffold preparation are high porosity with no usage of toxic solvents, good mechanical strength and flexibility of processing and material handling; however, its applicability to biodegradable polymers excludes a few, like PCL and PLA [104,133]. ...
Presently, millions worldwide suffer from degenerative and inflammatory bone and joint issues, comprising roughly half of chronic ailments in those over 50, leading to prolonged discomfort and physical limitations. These conditions become more prevalent with age and lifestyle factors, escalating due to the growing elderly populace. Addressing these challenges often entails surgical interventions utilizing implants or bone grafts, though these treatments may entail complications such as pain and tissue death at donor sites for grafts, along with immune rejection. To surmount these challenges, tissue engineering has emerged as a promising avenue for bone injury repair and reconstruction. It involves the use of different biomaterials and the development of three-dimensional porous matrices and scaffolds, alongside osteoprogenitor cells and growth factors to stimulate natural tissue regeneration. This review compiles methodologies that can be used to develop biomaterials that are important in bone tissue replacement and regeneration. Biomaterials for orthopedic implants, several scaffold types and production methods, as well as techniques to assess biomaterials’ suitability for human use—both in laboratory settings and within living organisms—are discussed. Even though researchers have had some success, there is still room for improvements in their processing techniques, especially the ones that make scaffolds mechanically stronger without weakening their biological characteristics. Bone tissue engineering is therefore a promising area due to the rise in bone-related injuries.
... [17]. Scaffoldbased methods are therefore receiving significant attention due to their versatility, the wide availability of both synthetic and natural polymers, and the obtainable three-dimensional porous structures, which facilitate cell growth, nutrient diffusion, tissue regeneration, and scaffold biodegradation [18][19][20][21][22][23][24][25]. ...
Cardiovascular diseases remain a leading cause of mortality globally, with atherosclerosis representing a significant pathological means, often leading to myocardial infarction. Coronary artery bypass surgery, a common procedure used to treat coronary artery disease, presents challenges due to the limited autologous tissue availability or the shortcomings of synthetic grafts. Consequently, there is a growing interest in tissue engineering approaches to develop vascular substitutes. This review offers an updated picture of the state of the art in vascular tissue engineering, emphasising the design of scaffolds and dynamic culture conditions following a biomimetic approach. By emulating native vessel properties and, in particular, by mimicking the three-layer structure of the vascular wall, tissue-engineered grafts can improve long-term patency and clinical outcomes. Furthermore, ongoing research focuses on enhancing biomimicry through innovative scaffold materials, surface functionalisation strategies, and the use of bioreactors mimicking the physiological microenvironment. Through a multidisciplinary lens, this review provides insight into the latest advancements and future directions of vascular tissue engineering, with particular reference to employing biomimicry to create systems capable of reproducing the structure–function relationships present in the arterial wall. Despite the existence of a gap between benchtop innovation and clinical translation, it appears that the biomimetic technologies developed to date demonstrate promising results in preventing vascular occlusion due to blood clotting under laboratory conditions and in preclinical studies. Therefore, a multifaceted biomimetic approach could represent a winning strategy to ensure the translation of vascular tissue engineering into clinical practice.
... Today, great attention is paid to developing printable materials (inks) that are mechanically strong, biocompatible and degradable and support tissue regeneration. Organ printing is a novel approach to cellbased tissue engineering allowing to create cell-laden hydrogel scaffolds with a tailored external shape and internal morphology [4]. ...
Recently, tissue engineering has been revolutionised by the development of 3D-printed scaffolds, which allow one to construct a precise architecture with tailored properties. In this study, three different composite materials were synthesised using a combination of polylactic acid (PLA), polyhydroxyalkanoates (PHA), poly(3-hydroxybutyrate) (PHB) and hydroxyapatite (HA) in varying weight percentages. Morphological properties were evaluated by scanning electron microscopy showing a uniform distribution of HA particles throughout the matrix, indicating good compatibility between the materials. Furthermore, the printed scaffolds were tested under pressure using a load cell to examine mechanical strength. Scanning electron microscopy (SEM) analysis showed favorable dispersion, biological compatibility together with enhanced bioactivity within the PHB/PHA/PLA/HA composite matrixes. Thus, this paper demonstrates the successful design and implementation of these composite structures for tissue-engineering applications and highlights the effective development of biocompatible scaffold designs with improved functionality.
... Despite the advantages of natural hydrogels such as good biocompatibility and low cytotoxicity [43], batch-to-batch variability, poor control over material properties, and difficulty in processing are serious barriers to their scaling up and implementation in clinical practice [35,44]. ...
Basic fibroblast growth factor (FGF2 or bFGF) is critical for optimal wound healing. Experimental studies show that local application of FGF2 is a promising therapeutic approach to stimulate tissue regeneration, including for the treatment of chronic wounds that have a low healing potential or are characterised by a pathologically altered healing process. However, the problem of low efficiency of growth factors application due to their rapid loss of biological activity in the aggressive proteolytic environment of the wound remains. Therefore, ways to preserve the efficacy of FGF2 for wound treatment are being actively developed. This review considers the following strategies to improve the effectiveness of FGF2-based therapy: (1) use of vehicles/carriers for delivery and gradual release of FGF2; (2) chemical modification of FGF2 to increase the stability of the molecule; (3) use of genetic constructs encoding FGF2 for de novo synthesis of protein in the wound. In addition, this review discusses FGF2-based therapeutic strategies that are undergoing clinical trials and demonstrating the efficacy of FGF2 for skin wound healing.
... In recent years, researchers have discovered an effective solution for repairing bone defects caused by diseases or trauma, using the power of additive manufacturing (3D-printing) and the outstanding properties of titanium alloys, stainless steels and others. Specifically, Ti6Al4V is a titanium alloy with excellent biocompatibility, corrosion resistance, and combination of good load carrying capacity and toughness, make it the preferred choice for manufacturing of medical devices for orthopedic and dental applications [3][4][5]. ...
Existing implants used with Total Knee Arthroplasty (TKA), Total Hip Arthroplasty (THA), and other joint reconstruction treatments, have displayed premature failures and frequent needs for revision surgery in recent years, particularly with young active patients who represent more than 55% of all joint reconstruction patients. Bone cement and stress shielding have been identified as the major reasons for premature joint failures. A breakdown of the cement may happen, and revision surgery may be needed because of the aseptic loosening. The significant mismatch of stiffness properties of patient trabecular bones and metallic implant materials in joint reconstruction surgery results in the stress shielding phenomenon. This could lead to significant bone resorption and increased risk of bone fracture and the aseptic loosening of implants. The present project introduces an approach for development of customized cellular structures to match the mechanical properties and architecture of human trabecular bone. The present work aims at fulfilling the objectives of the introduced approach by exploring new designs of customized lattice structures and texture tailored to mimic closely patients’ bone anisotropic properties and that can incorporate an engineered biological press-fit fixation technique. The effects of various lattice design variables on the mechanical performance of the structure are examined through a systematic experimental plan using the statistical design of experiments technique and analysis of variance method. All tested lattice designs were explored under realistic geometrical, biological, and manufacturing constraints. Of the four design factors examined in this study, strut thickness was found to have the highest percent contribution (41%) regarding the structure stiffness, followed by unit cell type, and cell size. Strut shape was found to have the lowest effect with only 11% contribution. The introduced solution offers lattice structure designs that can be adjusted to match bone stiffness distribution and promote bone ingrowth and hence eliminating the phenomenon of stress shielding while incorporating biological press-fit fixation technique.
... It was discovered that the strength of these biocomposites decreased as the CaPO4 level increased [285]. However, the biocompatibility of such biocomposites increases as the CaPO4 filler causes an increased initial flash spread of serum proteins compared to more hydrophobic polymer surfaces [286]. Furthermore, experimental results of those biocomposites showed enhanced cellular activity and good cell-material interactions compared to the corresponding polymers alone [279]. ...
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.
... Tissue engineering is a perspective method to repair bone defects by a combination of biomaterial science, cell biology, and biomedical engineering. 8,9 Significantly, modifying osteogenic genes in bone marrow mesenchymal stem cells (BMSCs) has become a promising therapeutic approach. Currently, functional gene molecules such as DNA plasmid, 10,11 siRNA, 12 and miRNA 13 have been employed to bone tissue engineering. ...
Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR‐136‐5p or Smurf1 expression were transfected into BMSCs. The effects of miR‐136‐5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR‐136‐5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR‐136‐5p/BMSCs/β‐TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro‐CT and HE staining. Elevating miR‐136‐5p‐3p or suppressing Smurf1 could stimulate OD of BMSCs. miR‐136‐5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR‐136‐5p on the OD of BMSCs. miR‐136‐5p/BMSCs/β‐TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1‐targeting miR‐136‐5p‐modified BMSCs combined with 3D‐printed β‐TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.
... Most of the current spherical microcarriers are biodegradable, allowing for the match between tissue formation and material degradation. Generally, natural polymers are more biocompatible, but the degradation rate of synthetic polymers is more easily modulated by molecular weight and chemical composition [183,184]. Meanwhile, depending on the size of the defect and the animal model, choosing microcarriers with sizes in a narrow range can effectively prevent cellular nutrient deficiency at the scaffold center. ...
Microcarrier applications have made great advances in tissue engineering in recent years, which can load cells, drugs, and bioactive factors. These microcarriers can be minimally injected into the defect to help reconstruct a good microenvironment for tissue repair. In order to achieve more ideal performance and face more complex tissue damage, an increasing amount of effort has been focused on microcarriers that can actively respond to external stimuli. These microcarriers have the functions of directional movement, targeted enrichment, material release control, and providing signals conducive to tissue repair. Given the high controllability and designability of magnetic and electroactive microcarriers, the research progress of these microcarriers is highlighted in this review. Their structure, function and applications, potential tissue repair mechanisms, and challenges are discussed. In summary, through the design with clinical translation ability, meaningful and comprehensive experimental characterization, and in-depth study and application of tissue repair mechanisms, stimuli-responsive microcarriers have great potential in tissue repair.
... In this technique, a 3D printer extrudes and deposits a thermoplastic material in a molten state through a nozzle, layer by layer, to create a 3D scaffold or structure [5]. Material extrusion 3D printing offers precise control over scaffold design and has shown promising applications in various tissue engineering applications, including cartilage [6], bone [7], skin [8], and vascular tissues [9]. ...
The significance of rheology in the context of bio three-dimensional (3D) printing lies in its impact on the printing behavior, which shapes material flow and the layer-by-layer stacking process. The objective of this study is to evaluate the rheological and printing behaviors of polycaprolactone (PCL) and dimethyl sulfone (DMSO2) composites. The rheological properties were examined using a rotational rheometer, employing a frequency sweep test. Simultaneously, the printing behavior was investigated using a material extrusion 3D printer, encompassing varying printing temperatures and pressures. Across the temperature range of 120–140 °C, both PCL and PCL/DMSO2 composites demonstrated liquid-like behavior, with a higher loss modulus than storage modulus. This behavior exhibited shear-thinning characteristics. The addition of DMSO2 10, 20, and 30 wt% into the PCL matrix reduced a zero-shear viscosity of 33, 46, and 74% compared to PCL, respectively. The materials exhibited extrusion velocities spanning from 0.0850 to 6.58 mm/s, with velocity being governed by the reciprocal of viscosity. A significant alteration in viscosity by temperature change directly led to a pronounced fluctuation in extrusion velocity. Extrusion velocities below 0.21 mm/s led to the production of unstable printed lines. The presence of distinct viscosities altered extrusion velocity, flow rate, and strut diameter. This phenomenon allowed the categorization of pore shape into three zones: irregular, normal, and no-pore zones. It underscored the importance of comprehending the rheological aspects of biomaterials in enhancing the overall quality of bio-scaffolds during the 3D printing process.
... An important property of the scaffold is that it should mimic the natural extracellular matrix (ECM) until the cells populating the scaffold synthesize their own ECM [19]. Therefore, the scaffold should have similar properties to natural bone regarding its three-dimensional porous structure, biocompatibility and bioresorbability, and surface texture for appropriate cell migration and proliferation [20]. Bone ECM plays an important role for cell adhesion, proliferation and the regulation of many biological functions like responses to growth factors and differentiation. ...
In certain situations, bones do not heal completely after fracturing. One of these situations is a critical-size bone defect where the bone cannot heal spontaneously. In such a case, complex fracture treatment over a long period of time is required, which carries a relevant risk of complications. The common methods used, such as autologous and allogeneic grafts, do not always lead to successful treatment results. Current approaches to increasing bone formation to bridge the gap include the application of stem cells on the fracture side. While most studies investigated the use of mesenchymal stromal cells, less evidence exists about induced pluripotent stem cells (iPSC). In this study, we investigated the potential of mouse iPSC-loaded scaffolds and decellularized scaffolds containing extracellular matrix from iPSCs for treating critical-size bone defects in a mouse model. In vitro differentiation followed by Alizarin Red staining and quantitative reverse transcription polymerase chain reaction confirmed the osteogenic differentiation potential of the iPSCs lines. Subsequently, an in vivo trial using a mouse model (n = 12) for critical-size bone defect was conducted, in which a PLGA/aCaP osteoconductive scaffold was transplanted into the bone defect for 9 weeks. Three groups (each n = 4) were defined as (1) osteoconductive scaffold only (control), (2) iPSC-derived extracellular matrix seeded on a scaffold and (3) iPSC seeded on a scaffold. Micro-CT and histological analysis show that iPSCs grafted onto an osteoconductive scaffold followed by induction of osteogenic differentiation resulted in significantly higher bone volume 9 weeks after implantation than an osteoconductive scaffold alone. Transplantation of iPSC-seeded PLGA/aCaP scaffolds may improve bone regeneration in critical-size bone defects in mice.
... Conventional methods of manufacturing porous scaffolds include foam rendering, solvent casting, and freeze-drying [21]. These methods provide limited control over scaffold chemistry, macrostructure, and porosity. ...
The reconstruction of bone deficiencies remains a challenge due to the limitations of autologous bone grafting. The objective of this study is to evaluate the bone regeneration efficacy of additive manufacturing of tricalcium phosphate (TCP) implants using lithography-based ceramic manufacturing (LCM). LCM uses LithaBone TCP 300 slurry for 3D printing, producing cylindrical scaffolds. Four models of internal scaffold geometry were developed and compared. The in vitro studies included cell culture, differentiation, seeding, morphological studies and detection of early osteogenesis. The in vivo studies involved 42 Wistar rats divided into four groups (control, membrane, scaffold (TCP) and membrane with TCP). In each animal, unilateral right mandibular defects with a total thickness of 5 mm were surgically performed. The animals were sacrificed 3 and 6 months after surgery. Bone neoformation was evaluated by conventional histology, radiology, and micro-CT. Model A (spheres with intersecting and aligned arrays) showed higher penetration and interconnection. Histological and radiological analysis by micro-CT revealed increased bone formation in the grafted groups, especially when combined with a membrane. Our innovative 3D printing technology, combined with precise scaffold design and efficient cleaning, shows potential for bone regeneration. However, further refinement of the technique and long-term clinical studies are crucial to establish the safety and efficacy of these advanced 3D printed scaffolds in human patients.
... Some, like bisphenol A (BPA), raise concerns about endocrine disruption and potential carcinogenicity [50]. Others, like thiols, may exhibit cytotoxicity at high concentrations [51]. Choosing safe and biocompatible monomers becomes the first line of defense in minimizing polymer toxicity. ...
Organosulfur-based polymers have unique properties that make them useful for targeted and managed drug delivery, which can improve therapy while reducing side effects. This work aims to provide a brief review of the synthesis strategies, characterization techniques, and packages of organosulfur-based polymers in drug delivery. More importantly, this work discusses the characterization, biocompatibility, controlled release, nanotechnology, and targeted therapeutic aspects of these important structural units. This review provides not only a good comprehension of organosulfur-based polymers but also an insightful discussion of potential future prospectives in research. The discovery of novel organosulfur polymers and innovations is highly expected to be stimulated in order to synthesize polymer prototypes with increased functional accuracy, efficiency, and low cost for many industrial applications.
... Resorptionsprozess einsetzt und körpereigenes Gewebe deren Funktion schrittweise übernimmt. Knochen-Scaffolds werden durch Verfahren der additiven Fertigung 3D-gedruckt, was die patientenspezifische Konfiguration der Implantatarchitektur ermöglicht [9]. So können die notwendige Gewebe(neu)formation und -regeneration über einen Zeitraum bis zu einigen Jahren Jedoch werden trotz intensiver Forschung -im Jahr 2023 wurden immerhin mehr als 20.000 Studien zum Thema Knochen-Scaffolds und Knochen-Tissue-Engineering veröffentlicht -nur eine Handvoll Innovationen insofern in die klinische Praxis umgesetzt, dass diese tatsächlich "from bench to bedside" gelangen [11,12]. ...
... 9 Replicating this complexity in a laboratory setting proves to be a daunting task. 10,11 In addition, the customization potential of bioprinting introduces significant regulatory challenges. Navigating the regulatory landscape for personalized bioprinted products is complex, as current frameworks are primarily designed for mass-produced medical devices and pharmaceuticals. ...
Biofabrication, broadly described as “a process that results in a defined product with biological function,” has undergone a revolution in recent years. This revolution has led to an explosion of literature containing valuable data and insights on bioactive materials and machine learning-aided design. However, the accessibility and comprehension of this rich data source remain a challenge, necessitating the creation of a comprehensive database. Herein, we present the manufacturing multi-organs database (MMDB), a real-time updating database developed to foster an all-inclusive understanding of biofabrication by leveraging machine learning for standardized analysis of material properties and manufacturing processes. The MMDB aids in identifying commonly used cells, materials, and culture strategies in biofabrication by analyzing over 5000 papers related to 37 human organs. Leveraging machine learning models, it predicts optimal printing parameters and organ functionality metrics, thereby streamlining experimental designs and reducing costs. In addition, MMDB offers knowledge services that encompass hotspot analysis, trend identification, international collaboration analysis, and comprehensive knowledge maps of organ functions and biomaterials. We believe that the MMDB, serving as a crucial and readily accessible knowledge base, will fundamentally facilitate the design and optimization of biofabrication experiments. Moreover, by accelerating the discovery of optimal parameters, the MMDB has the potential to offer invaluable insights into organ function, propelling the field of biofabrication toward more efficient and effective organ manufacturing.
... PCL is a biodegradable polymer widely used in biomedical applications (Scaffaro et al. 2016a), for the expansion of bioprocesses (Scaffaro et al. 2016b), and in tissue engineering, mainly as a matrix material in composites (Arif et al. 2022). The applicability of PCL in hard-tissue repair is restricted by the high elongation at break and relatively low elastic modulus of ductile polymers (Hutmacher 2000). All of these factors have led to numerous scientific studies that have focused on the creation of high-performance electrospun PCL scaffolds, such as biopolymer blends (Bauer et al. 2016), and the utility of nanofillers (Ghorbani et al. 2015). ...
Bioabsorbable and biodegradable composites have experienced rapid growth, owing to their high demand in the biomedical sector. Polymer-cellulose nanocrystal (CNC) compounds were developed using a medical-grade poly (ε-caprolactone) (PCL) matrix to improve the stiffness and load-bearing capacity of pure PCL. Five PCL/CNCs filament grades were melt-extruded, pelletized, and fed into an industrial bioplotter to fabricate specimens. To assess the effects of CNCs on pure PCL, 14 tests were conducted, including rheological, thermomechanical, and in situ micro-mechanical testing, among others. The porosity and dimensional accuracy of the samples were also documented using micro-computed tomography while scanning electron microscopy was employed for morphological characterization. Overall, the 4.0 wt % CNCs loading accomplished the optimum mechanical response, with an increase in its tensile (19.1%) and flexural strength (12.6%) compared to pure PCL. Concurrently, this grade exhibited the highest MFR, minimum porosity, and highest nominal-to-actual geometric accuracy, thereby convincingly interpreting the reinforcement mechanisms.
This study aimed to address a significant challenge in the application of bacterial cellulose (BC) within tissue engineering and regenerative medicine by tackling its inherent insolubility in water and organic solvents. Our team introduced a groundbreaking approach by utilizing zinc sulfate (ZnSO 4 ) as a solvent to render BC soluble, a novel contribution to the literature. Subsequently, the obtained soluble BC was combined with varying concentrations of polyvinylpyrrolidone (PVP). Notably, we pioneered the fabrication of BC/PVP composite scaffolds with customizable fiber surface morphology and regulated degradation rates through the electrospun technique. Several key parameters, such as PVP concentration (8%, 15%, 12%, and 20% w/v), applied voltage (22, 15, and 12 kV), and a fixed nozzle‐collector distance of 10 cm with a flow rate of 0.9 mL/h, were systematically evaluated so as to find the optimum parameter created BC/PVP product with electrospun. For electrospun BC/PVP products, a voltage of 12 kV was found to be optimal. Intriguingly, our findings revealed enhanced cell adhesion and proliferation in BC/PVP electrospun products compared with using PVP membranes alone. Specifically, cell viability for PVP and PVP/BC electrospun products was determined as 50.73% and 79.95%, respectively. In terms of thermal properties, the BC/PVP electrospun product exhibited a mass loss of 82.6% at 380°C, while PVP alone experienced 90.2% mass loss at around 280°C. Furthermore, the protein adhesion capacities were measured at 62.3 ± 1.2 μg for PVP and 99.4 ± 2 μg for BC/PVP electrospun products, whereas product showed no biodegradation over 28 days and had notable water retention capacity. In conclusion, our research not only successfully attained nanofiber morphology but also showcased enhanced cell attachment and proliferation on the BC/PVP electrospun product.
Three-dimensional printed porous scaffolds offer biophysical and biochemical support for surrounding cells, mimicking the extracellular matrix (ECM) in bone tissue engineering. Bone tissue engineering scaffold is intended to provide hydrophilicity, cytocompatibility and delivery of diverse bioactive molecules such as growth factors and enzymes to exhibit cell attachment, proliferation, osteogenic differentiation and calcification. Alkaline phosphatase enzyme is an essential biomolecule due to its significant role in bone mineralization and cell differentiation. This study immobilizes alkaline phosphatase enzyme (ALP) and dopamine on a 3D-printed polycaprolactone/TiO 2 nanocomposite via solvent soaking. Characterization includes contact angle, compressive strength test, EDX, ATR, and XRD analysis. In vitro cell studies on PCL, PCL/nTiO 2 , PCL/nTiO 2 /Dopamine, and PCL/nTiO 2 /dopamine/ALP 3D-printed scaffolds evaluate osteogenic differentiation and cell viability using ALP activity on rat adipose-derived mesenchymal stem cells (MSCs) and MTT assay on the L929 cell line. FTIR confirms nanoparticle presence in the scaffold, while XRD and compressive tests show that the crystallinity degree and mechanical properties of the PCL scaffold are higher than nanocomposite scaffolds. Dopamine increases the hydrophilicity of PCL, enhancing biological behavior and expressing significant osteogenic effects. The PCL/nTiO2/Dopamine/ALP group shows the most ALP activity after 3 days. ALP assay exhibits acceptable differentiation in the absence of ALP for nanocomposite scaffolds after 7 days of incubation. TiO 2 considerably increases osteogenic differentiation after 10 days, up to about 100%, compared to the sample containing osteogenic medium. This study highlights the potential for designing novel biofunctionalized 3D nanocomposite scaffolds with osteogenic properties for bone tissue engineering applications.
The integration of scaffolds, signalling cues, and cellular components is essential in tissue engineering to create an in vivo equivalent environment that supports physiological function. Scaffolds provide mechanical reinforcement for cellular proliferation and differentiation while providing cues that instruct the development of cells during culture. Alginate (Alg) is a versatile biopolymer for scaffold engineering. However, due to a lack of intrinsic cell-binding sites, thus far, Alg must be functionalized for cellular adhesion. Here, we demonstrate proof-of-concept, bioactive additive-free, microstructured Alg (M-Alg) scaffolds for neuron culture. The M-Alg scaffold was formed by introducing tetrapod-shaped ZnO (t-ZnO) microparticles as structural templates in the Alg that were subsequently removed. These transparent, porous, additive-free Alg-based scaffolds with neuron affinity are promising for neuroregenerative and organoid- related research.
Highlights
Tetrapod-shaped ZnO (t-ZnO) microparticles are used as a template for the fabrication of open interconnected channels and textured surfaces in 3D printed microstructured alginate (M-Alg) scaffolds.
Primary mouse cortical neurons seeded on the 3D printed M-Alg scaffolds show improved adhesion and maturation with extensive neural projections forming inside the scaffolds.
Shape-morphing hydrogels have emerged as a promising biomaterial due to their ability to mimic anisotropic tissue composition by creating an out-of-plane and in-plane gradient due to differences in local swelling...
Cellulose nanocrystal (CNC), as a renewable resource, with excellent mechanical performance, low thermal expansion coefficient, and unique optical performance, is becoming a novel candidate for the development of smart material. Herein, the recent progress of CNC‐based chirality nanomaterials is uncovered, mainly covering structure regulations and function design. Undergoing a simple evaporation process, the cellulose nanorods can spontaneously assemble into chiral nematic films, accompanied by a vivid structural color. Various film structure‐controlling strategies, including assembly means, physical modulation, additive engineering, surface modification, geometric structure regulation, and external field optimization, are summarized in this work. The intrinsic correlation between structure and performance is emphasized. Next, the applications of CNC‐based nanomaterials is systematically reviewed. Layer‐by‐layer stacking structure and unique optical activity endow the nanomaterials with wide applications in the mineralization, bone regeneration, and synthesis of mesoporous materials. Besides, the vivid structural color broadens the functions in anti‐counterfeiting engineering, synthesis of the shape‐memory and self‐healing materials. Finally, the challenges for the CNC‐based nanomaterials are proposed.
Gingival Ünite Greftinin Periodontal Plastik Cerrahide Kullanımı Ezgi GÜRBÜZ Zeki KAÇAR Damla Kan KARABIYIK Fatma KAVRUK Gerodontoloji ve Periodontal Durum Yasemin Beliz ÖNDER Dicle ALTINDAL Dental Mikrocerrahinin Gelişimi ve Periodontolojide Kullanımı Özlem SARAÇ ATAGÜN Periodontal Doku Mühendisliğinde Yeni Yaklaşımlar Eda ÇETİN ÖZDEMİR İmplant Tedavisi Açısından Canalis Sinuosusun Konik Işınlı Bilgisayarlı Tomografi ile Değerlendirilmesi Emrah BİLEN Hamide DURSUN ZAHİTOVİC Periodontitis ve Romatoid Artrit Başak BIYIKOĞLU Tümer TEKİN Dental İmplant Başarısızlığının Etiyolojisi ve Yönetimi Sema Nur Sevinç GÜL Ladise Ceylin HAS Endodontik Periodontal Lezyonlar Sema Nur SEVİNÇ GÜL Faezeh NADERLOU Dişeti Çekilmelerinde Güncel Tedavi Yaklaşımları Egemen TAYAN Periodontal Hastalıklar ve Covid-19 Arasındaki İlişki Egemen TAYAN Ceren GÖKMENOĞLU
Glycosaminoglycans (GAGs) are ubiquitous components in the cartilage extracellular matrix (ECM). Ultrastructural arrangement of ECM and GAG-mediated interactions with collagen are known to govern the mechanics in articular cartilage, but these interactions are less clear in other cartilage types. Therefore, this article reviews the current literature on ultrastructure of articular, auricular, meniscal, and nasal septal cartilage, seeking insight into GAG-mediated interactions influencing mechanics. Ultrastructural features of these cartilages are discussed to highlight differences between them. GAG-mediated interactions are reviewed under two categories: interactions with chondrocytes and interactions with other fibrillar macromolecules of the ECM. Moreover, efforts to replicate GAG-mediated interactions to improve mechanical integrity of tissue-engineered cartilage constructs are discussed. In conclusion, studies exploring cartilage specific GAGs are poorly represented in the literature, and the ultrastructure of nasal septal and auricular cartilage is less studied compared with articular and meniscal cartilages. Understanding the contribution of GAGs in cartilage mechanics at the ultrastructural level and translating that knowledge to engineered cartilage will facilitate improvement of cartilage tissue engineering approaches.
Bioinspired strategies for scaffold design and optimization were improved by the introduction of Additive Manufacturing (AM), thus allowing for replicating and reproducing complex shape and structures in a reliable manner,...
The repair of critical-sized bone defect caused by trauma or disease poses a remarkable clinical challenge. Even though conventional methods such as autografts and allografts have been commonly used, they each have corresponding shortcomings limiting their clinical application. Generally, existing biomaterials such as metals and cements cannot meet the clinical needs. Therefore, there is a critical need for the development of biomimetic and bioactive three-dimensional (3D) scaffolds for bone regeneration. The use of hydrogels is considered a promising strategy in bone tissue engineering due to their highly aqueous 3D network structure and functional characteristics. This chapter focuses on use of natural and synthetic hydrogel scaffolds inspired by extracellular matrix (ECM) biology and structure for bone tissue engineering. Firstly, we discuss the requirements of hydrogel substitutes, the type of hydrogels used and their properties, as well as the combination of hydrogels with growth factors, cells, drugs, and inorganic components. Afterwards, current fabrication strategies are presented, with the emphasis on the implantable hydrogels and injectable hydrogels. Finally, the current challenges, considerations, and future directions are discussed in order to provide new directions for the design and clinical use of hydrogel scaffolds in bone regeneration. We believe that recent advances in the multifunctional bioactive hydrogels offer important information to researchers in the field and clinicians to generate new perspectives on bone repair.
Polycaprolactone (PCL) scaffolds were fabricated using the solvent casting and particulate leaching techniques, using sodium chloride (NaCl) particles ranging in size from 425 to 450 µm, as the porogen. Curcuma comosa extract (CC) utilized in this study has anti-inflammatory, anti-oxidative, anti-atherosclerotic, and estrogenic properties that benefit both skin and bone tissues. PCL scaffolds were immersed in a CC solution to create CC-loaded scaffolds. The PCL to NaCl weight ratios varied between 1:8, 1:10, and 1:12, while the concentration of CC was either 0.5 or 1.0 mg/mL. Based on the findings, the pore diameters of the neat and CC-loaded PCL scaffolds ranged from 280 to 332 µm. Increasing NaCl content resulted in the scaffolds being more porous, thus having low compressive moduli and releasing high amounts of CC. Both water retention and weight loss of the scaffolds increased with an increasing submersion time in a buffer solution. These scaffolds released no substances that were detrimental to both mouse fibroblast (NCTC clone 929) and mouse osteoblast (MC3T3-E1) cells. While the presence of CC in the PCL scaffolds showed no significant effect on the attachment of MC3T3-E1 cells, it significantly supported their proliferation. All these suggested that the CC-loaded PCL scaffolds could be used as cartilage scaffolding materials.
Recently, we attempted to optimize the microstructures of composite materials, composed of collagen fibers and hydroxyapatite (HAp) particles, by mimicking bone microstructures. This study further investigates these materials to clarify how the tensile strength of the HAp/collagen composite fiber bundles is affected by the electric current used during their preparation via electrophoresis. The collagen fiber preparation and HAp deposition were carried out using the bioinspired method and biomimetic deposition, respectively. The tensile strength was evaluated by micromechanical testing. The tensile strength of collagen fiber bundles and HAp/collagen composite fiber bundles increased and then decreased with increasing electric current. This indicated a trade-off relationship between tensile strength and bundling. The optimal electrophoresis current value was determined to be 4–5 mA. Additionally, the optimal method to introduce the adhesive protein to the bundles was discussed.
The synthesis, characterization, and ring-opening polymerization (ROP) activity of a family of niobium and tantalum alkoxide catalysts was studied.
Large bone defects are the leading contributor to disability worldwide, affecting approximately 1.71 billion people. Conventional bone graft treatments show several disadvantages that negatively impact their therapeutic outcomes and limit their clinical practice. Therefore, much effort has been made to devise new and more effective approaches. In this context, bone tissue engineering (BTE), involving the use of biomaterials which are able to mimic the natural architecture of bone, has emerged as a key strategy for the regeneration of large defects. However, although different types of biomaterials for bone regeneration have been developed and investigated, to date, none of them has been able to completely fulfill the requirements of an ideal implantable material. In this context, in recent years, the field of nanotechnology and the application of nanomaterials to regenerative medicine have gained significant attention from researchers. Nanotechnology has revolutionized the BTE field due to the possibility of generating nanoengineered particles that are able to overcome the current limitations in regenerative strategies, including reduced cell proliferation and differentiation, the inadequate mechanical strength of biomaterials, and poor production of extrinsic factors which are necessary for efficient osteogenesis. In this review, we report on the latest in vitro and in vivo studies on the impact of nanotechnology in the field of BTE, focusing on the effects of nanoparticles on the properties of cells and the use of biomaterials for bone regeneration.
Bioactive glass (BG)–polymer composites are promising materials for bone grafting in bone tissue regeneration. BG provides rigidity and can initiate bone growth, whereas the polymer matrix provides flexibility and biocompatibility. However, due to the complex composition of BG, incorporation into the polymer matrix is difficult and often leads to unwanted porosity and low interface strength between both components. In this study, we investigate the surface treatment of commercially available micronized melt-derived BG with varying compositions (45S5 and 1393) to improve its incorporation into a poly(lactic-co-glycolic acid) (PLGA) matrix by improving surface roughness, surface charge and active sites on the BG. The surfaces of BG are modified by treatment in simulated body fluid (SBF) for 3 days prior to composite production. This leads to the formation of carbonated hydroxyapatite on the surface of both BG types, as demonstrated by XRD, FTIR, XPS and EDX. This also leads to a change in surface texture and an increase in specific surface area from initially 3 to 116 m² g⁻¹ and from 2 to 65 m² g⁻¹ for 45S5 and 1393, respectively. Subsequently, composite PLGA–BG microspheres are fabricated using a probe-ultrasonication assisted solid-in-oil-in-water emulsion method. Additionally, the surface interaction of bioactive glasses with PLGA is discussed in detail.
In contrast to the freeze-drying process, the rehydration process of freeze-dried foods remains unclear. This study investigated the rehydration of freeze-dried soybean curd, also known as tofu, and elucidated its breakage mechanism during rehydration, which impairs texture. The rehydration of freeze-dried tofu was observed at different water temperatures (20, 40, 70, and 100 ℃), with the required rehydration time found to decrease with increasing water temperature. Furthermore, tofu was found to absorb water faster in cracks formed during production than in the porous body. Crack expansion was observed only in high-temperature water, leading to breakage of the tofu. Environmental scanning electron microscopy revealed that tofu expanded when a sufficient amount of water was absorbed. Accordingly, crack expansion in high-temperature water is attributed to the stress concentration at the tip of the crack, which is caused by differences in the rehydration rate and resulting stiffness between the porous body and cracks.
A photo-crosslinked nanocomposite hydrogel was prepared by incorporating an osteo-inductive inorganic nanoparticle for endogenous bone regeneration.
In vitro skin models are validated methods for screening cosmetics and pharmaceuticals, but still have limitations. The bilayer poly(ε‐caprolactone) scaffold/membrane model described here overcomes some of these deficits by integrating a solution electrospun (SES) membrane at the dermoepidermal interface and a melt electrowritten (MEW) scaffold that provides an optimal open‐pore environment for the dermis. To the knowledge, this scaffold/membrane model is the only one capable of creating a properly differentiated, full thickness skin model with neosynthesized extracellular matrix (ECM) in only 18 days. Both the wavy and straight fiber scaffold designs create a well‐organized dermis, but dermal collagen organization differs between designs. Adding cells and vitamin C to the scaffolds improves the mechanical properties to more closely mimic native human skin. These findings establish bicomponent scaffolds as a promising advancement for rapidly creating different skin models with varied properties. The versatility and adaptability of the described model can be used for studying how the biological and physical microenvironment impact skin, and testing dermo‐cosmetics and pharmaceutical treatments on different ages of skin. Furthermore, it can be an excellent new tool for studying wound healing and development into its use as a graft or wound dressing is ongoing.
Biodegradable rods of polyglycolide or lactide-glycolide copolymer were used in the internal fixation of a variety of fractures and osteotomies in 516 patients. A clinically manifest foreign-body reaction occurred in 41 patients (7.9%), producing a fluctuant swelling at the implantation site after an average of 12 weeks. Spontaneous sinus formation or surgical drainage yielded a sterile exudate containing liquid remnants of the degrading implants. After prompt drainage this discharge subsided within three weeks. Histological examination showed a typical nonspecific foreign-body reaction with abundant giant cells both in patients with the reaction and in some patients with an uneventful clinical course. The factors determining the nature of the reaction were probably related to the local capacity of the tissues to clear the polymeric debris. The reactions did not influence the clinical or radiographic results, but recognition of the incidence and the features of the reaction is necessary in view of the increasing use of such implants.
Synthetic polymer scaffolds designed for cell transplantation were reproducibly made on a large scale and studied with respect to biocompatibility, structure and biodegradation rate. Polyglycolic acid (PGA) was extruded and oriented to form 13 microns diameter fibers with desired tenacity. Textile processing techniques were used to produce fibrous scaffolds with a porosity of 97% and sufficient structural integrity to maintain their dimensions when seeded with isolated cartilage cells (chondrocytes) and cultured in vitro at 37 degrees C for 8 weeks. Cartilaginous tissue consisting of glycosaminoglycan and collagen was regenerated in the shape of the original PGA scaffold. The resulting cell-polymer constructs were the largest grown in vitro to date (1 cm diameter x 0.35 cm thick). Construct mass was accurately predicted by accounting for accumulation of tissue components and scaffold degradation. The scaffold induced chondrocyte differentiation with respect to morphology and phenotype and represents a model cell culture substrate that may be useful for a variety of tissue engineering applications.
Poly(L-lactic acid) and its copolymers with D-lactic and glycolic acid were used to fabricate various porous biodegradable scaffolds suitable for tissue engineering and drug delivery based on a thermally induced phase separation (TIPS) technique. A variety of parameters involved in TIPS process, such as types of polymers, polymer concentration, solvent/nonsolvent ratio, and quenching temperature, were examined in detail to produce a wide array of micro- and macroporous structures. A mixture of dioxane and water was used for a binary composition of solvent and nonsolvent, respectively In particular, the coarsening effect of pore enlargement affected by controlling the quenching temperature was used for the generation of a macroporous open cellular structure with pore diameters above 100 mu m. The use of amorphous polymers with a slow cooling rate resulted in a macroporous open cellular structure, whereas that of semicrystalline polymers with a fast cooling rate generated a microporous closed cellular structure. The fabricated porous devices loaded with recombinant human growth hormone (rhGH) were tested for the controlled delivery of rhGH, as a potential additional means to cell delivery. (C) 1999 John Wiley & Sons, Inc.
Three Dimensional Printing is a process for the manufacture of tooling and functional prototype parts directly from computer models. Three Dimensional Printing functions by the deposition of powdered material in layers and the selective binding of the powder by “link-jet” printing of a binder material. Following the sequential application of layers, the unbound powder is removed, resulting in a complex threedimensional part. The process may be applied to the production of metal, ceramic, and metal-ceramic composite parts. An experiment employing continuous-jet ink-jet printing technology has produced a three-dimensional ceramic part constructed of 50 layers, each 0.005 in. thick. The powder is alumina and the binder is colloidal silica. The minimum feature size is 0.017 in., and features intended to be 0.5000 in. apart average 0.4997 in. apart in the green state and 0.5012 in. apart in the cured state, with standard deviations of 0.0005 in. and 0.0018 in., respectively. Future research will be directed toward the direct fabrication of cores and shells for metal casting, and toward the fabrication of porous ceramic preforms for metal-ceramic composite parts.
Biomaterials are substances that are used in prostheses or in medical devices designed for treatment, augmentation, or replacement any tissue, organ or function of the body. Both natural and synthetic materials are used as biomaterials.
In the not too distant past, organ transplantation was considered a futuristic concept. However, things considered miraculous in one era may be merely remarkable in another (Langer and Vacanti, 1995). Over the last half of this century, development of techniques for tissue and organ transplantation have been revolutionary. Along with the tremendous advances in the field of transplantation, new problems have emerged needing solutions. It is in this context that the field of tissue engineering has emerged over the last decade (Vacanti and Vacanti, 1996).
Tissue engineering, which includes the development of replacements for damaged or diseased tissues and organs, is a rapidly growing new field that draws upon the expertise of chemists, chemical engineers, and materials scientists in addition to biologists and physicians. Polymeric biomaterials have played an important role thus far in tissue engineering and hold great promise for future applications. Some of the uses of polymeric biomaterials in tissue engineering have included immunoprotective membranes for cell transplantation (Pathak et al, 1992; Sefton et al, 1987) and scaffolds to support and guide tissue growth (Cima et al, 1990; Freed et al, 1994; Mooney et al, 1995).
In reviewing the scientific literature of hard-tissue repair/generation, it can be concluded that it is worthwhile to evaluate the possibility of obtaining synergistic effects by combining bioresorbable scaffolds with other factors stimulatory to osteogenesis. Theoretically, this can occur at different principal levels. Cytokines, including growth factors such as BMP, the IGFs, TGF-b, PDGF, may be stimulatory to the differentiation of cells of the osteoblastic lineage, thus having the potential to promote an increased recruitment of osteogenic cells. The IGFs, TGF-b, and PDGF are known to stimulate the synthetic capacity of mature osteoblasts. In addition, the FGFs are angiogenic and may thus improve nutrition for a healing bone defect by an early establishment of the vascular bed. At present, the field of growth-stimulatory factors is strongly expanding. Even though the effects on bone of such factors are far from being completely elucidated, it may be expected that some of them will be of clinical relevance in the future. Future developments of de novo biodegradable and bioresorbable carrier and matrix materials treated with growth factors should have the objectives: biointeractive and biomi-metic devices/implants endowed with cell or cell-based signals; a synthetic extracellular matrix for enhanced cell interaction, cell polarization, or remodeling; and a temporal and/or spatial delivery of bioactive agents over short and long time-periods.
Building on the knowledge base of conventional tissue grafts and disparate fields of science and engineering, great strides have been made in the field of tissue engineering with regard to replacement and assembly of functional tissue equivalents. The development of tissue-engineered constructs (TECs) involves a complex underlying interplay of mechanisms. A case in point is the provision of a microvasculature. What nature appears to readily provide has become a crux in the current TEC design. To be sure, the future design of clinically translatable TECs will continue to involve multidisciplinary research and training to address the current and future design limitations realized with TECs. Many current design limitations are not insurmountable, but only require innovative approaches and/or development of new technologies. Once titanium alloys were the implant scaffolds of choice. But today there are biodegradable polymers, “smart” polymers, and biomimetic materials. The future for the development of clinically translatable TECs is just beginning to be fathomed.
Organ or tissue failure remains a frequent, costly, and serious problem in health care despite advances in medical technology. The large number of patients suffering from tissue losses or organ failures is demonstrated by the approximately 8 million surgical procedures and 40 to 90 million hospital days required annually to treat these problems (Langer and Vacanti, 1993). Available treatments now include transplantation of organs from one individual to another, performing surgical reconstruction, use of mechanical devices (e.g., kidney dialyzer), and drug therapy. However, these treatments are not perfect solutions. Transplantation of organs is limited by the lack of organ donors, possible rejection, and other complications. For example, there are only 3000 donors available in contrast to 30,000 patients who die from liver failure each year (American Liver Foundation, 1988). Mechanical devices cannot perform all functions of an organ, e.g., kidney dialysis can only help remove some metabolic wastes from the body. Likewise, drugs can only replace limited biochemical functions of an organ or tissue, and physiologic control of drug levels comparable to the control systems of the body is difficult to achieve. For example, although diabetes can be partially treated by administration of insulin, it is still the leading cause of chronic renal failure and blindness (Chukwuma, 1995; Hoelscher et al, 1995; Sander and Wilson, 1993). This is partly due to difficulties in controlling the drug level in vivo (Levesque et al, 1992). Financially, the cost of surgical procedures is very high ($150,000 for a liver transplant). It is estimated that almost half of the United States $800 billion in annual health care costs are due to loss or malfunction of tissue or organs (Langer and Vacanti, 1993).
The science of biodegradable materials is most often associated with problems of environmental control. The need to avoid accumulation of permanent ecological litter is obvious and methods to do so will not be considered in this discussion. Rather, the emphasis will be on polymers with the potential for degradation within the living organism. More specifically, polymers which display structural integrity and, as a consequence, mechanical utility, will be considered while polymeric drugs or carriers which function in solution, such as polyvinyl pyrollidone and dex-tran, both reported as useful blood extenders, will not.
A standard protocol is proposed which has been used to study comparatively the degradation mechanism of bioresorbable poly(~-hydroxy acids) with respect to macromolecular structural characteristics and solid-state morphologies. As a first approach, the hydrolytic degradation of poly(gL-lactic acid) (PLA50) parallelepipedic specimens (15mm x 10mm x 2mm), processed by compression moulding and machining, was investigated in two aqueous media: iso-osmolar saline and pH 7.4 phosphate buffer. Various techniques (namely weighing, size-exclusion chromatography (SEC), potentiometry, cryometry and enzymatic assay) have been applied to these specimens in order to monitor the degradation. Data show conclusively that the degradation of massive PLA50 specimens proceeds more rapidly in the centre than at the surface. This feature has been related to the formation of an outer layer of slowly degrading polymer, which is caused by surface phenomena and entraps degrading macromolecules. Only oligomers can diffuse and dissolve in the surrounding media. Accordingly, the number of carboxylic groups present in the inner part of the degrading specimens becomes larger than at the surface and accelerates ester bond cleavage. The resultant autocatalytic mechanism explains well the fact that partially degraded PLA50 exhibits bimodal SEC chromatograms although this polymer is amorphous.
Autogenous cell transplantation is one of the most promising new techniques being developed for bone generation as it eliminates problems of donor site scarcity, immune rejection and pathogen transfer. Osteoblasts obtained from an individual patient can be grown in culture and seeded onto a three-dimensional scaffold that will slowly degrade and resorb as the bone or cartilage structures grow and assimilate in vivo. The three-dimensional (3D) scaffold provides the necessary support for cells to maintain their differentiated state and defines the overall shape of the new bone and cartilage. The necessity of using a scaffold structure as the basic template of engineering tissues has encouraged the study the application of advanced manufacturing technologies in this field. For example, rapid prototyping (RP) technologies such as fused deposition modeling (FDM) can be used to fabricate complex 3D structures based on two-dimensional (2D) cross-sectional data obtained by slicing a computer-aided design (CAD) models. FDM is currently being applied in our laboratory to fabricate bioresorbable 3D scaffolds of various porosities and micro-architecture for tissue engineering bone.
Tissue engineering is a relatively new and emerging interdisciplinary field that applies the knowledge of bioengineering, the life sciences, and the clinical sciences in solving the critical medical problems of tissue loss and organ failure. It involves the application of engineering principles of transport and reaction phenomena, as well as methods of analysis to understand the complex biological processes that occur in tissue development and repair. Frequently, the knowledge of molecular phenomena and cellular interactions with surface, biochemical, and mechanical environments is employed. Tissue engineering has been formally defined as “the application of the principles and methods of engineering and the life sciences to the fundamental understanding of structure–function relationships in normal and pathological mammalian tissues and the development of biological substitutes that restore, maintain, or improve tissue function.” The donor scarcity, technical difficulties, expense, and complex labor-intensive care associated with conventional tissue and organ transplantation provide a significant impetus for the development of tissue-engineered therapies. Tissue engineering is a field with an enormous potential to make truly significant contributions to mankind over the next decades. As life expectancy continues to rise, the potential pool of recipients of tissue-engineered constructs is growing. Tissue-engineered products will be more available and cost-effective than donor organs. The problem of availability of a tissue-engineered product can normally be resolved using cell expansion culturing techniques.
A large variety of processes have been applied to manufacture scaffolds. However, there is no universal technique to produce scaffolds for the regeneration of all tissues. Often the requirements for a desired scaffold dictate the method of processing and the type of material used. This is dependent on the shape of a scaffold, the pore structure, a required degradation rate, drug delivery purposes, or the mechanical properties. In addition, different kinds of tissues require different scaffolds. For the repair of hard and brittle tissue, such as bone, scaffolds need to have a high elastic modulus to maintain the space designated to them and provide the tissue with enough space for growth. If scaffolds are used as a temporary load-bearing device, they should be strong enough to maintain that load for the required time without showing any symptoms of fatigue failure. Used in combination with soft tissues, the flexibility and the stiffness of the scaffold have to be within the same order of magnitude as the surrounding tissues in order to prevent the scaffold from either breaking or collapsing. The choice of a scaffold-processing technique is therefore a question of assessing critical requirements for each application of such scaffolds. However, many challenges remain in the fabrication of high load-bearing scaffolds, scaffolds with high flexibility, and the incorporation and delivery of drugs, bioactive molecules, and cells to stimulate and enhance the growth of a specific tissue.
Degradation of two lactic-glycolic copolymers, namely PLA37.5GA25 (75% DL-lactide and 25% glycolide in the feed) and PLA75GA25 (75% L-lactide and 25% glycolide) was investigated in vitro using aqueous media to model physiological conditions. Various techniques were used to monitor the effects due to hydrolytic degradation including weighing, SEC (size-exclusion chromatography), potentiometry, cryometry, enzymatic assay, X-ray scattering, H-1-nuclear magnetic resonance and differential scanning calorimetry. It was found that degradation proceeded faster in the centre than at the surface of standard parallelepipedic specimens. This feature had already been found for PLA50 (poly(DL-lactic acid)). The degradation rates of PLA37.5GA25 and PLA75GA25 were compared and it was found that intrinsically amorphous PLA75GA25 crystallized as degradation proceeded, in contrast to PLA37.5GA25. The crystallization of PLA75GA25 was related to the preferential degradation at glycolic units, which led to L-lactic-enriched fragments susceptible to crystallize. No major differences were observed between ageing in iso-osmolar saline and pH 7.4 phosphate buffer. In contrast, in the case of PLA37.5GA25, distilled water favoured surface-centre differentiation, probably because of osmotic exchange related to the absence of ionic strength.
Commercial solid freeform fabrication (SFF) systems, which have been developed for fabrication of wax and polymer parts for form and fit and secondary applications, such as moulds for casting, etc., require further improvements for use in direct processing of structural ceramic and metal parts. Defects, both surface as well as internal, are undesirable in SFF processed ceramic and metal parts for structural and functional applications. Process improvements are needed before any SFF technique can successfully be commercialized for structural ceramic and metal processing. Describes process improvements made in new SFF techniques, called fused deposition of ceramics (FDC) and metals (FDMet), for fabrication of structural and functional ceramic and metal parts. They are based on an existing SFF technique, fused deposition modelling (FDM) and use commercial FDM systems. The current state of SFF technology and commercial FDM systems results in parts with several surface and internal defects which, if not eliminated, severely limit the structural properties of ceramic and metal parts thus produced. Describes systematically, in detail, the nature of these defects and their origins. Discusses several novel strategies for elimination of most of these defects. Shows how some of these strategies have successfully been implemented to result in ceramic parts with structural properties comparable to those obtained in conventionally processed ceramics.
Focusses on preliminary studies on developing thermoplastic composite materials suitable for use in fused deposition modeling (FDM). Looks at thermotropic liquid crystalline polymers (TLCPs). Specifically aims to determine the feasibility of post-processing TLCP composite strands generated by means of the dual extrusion process using FDM to enhance the tensile properties and functionality of prototypes. Describes the experiments and gives in-depth results which include the finding that final mechanical properties of a composite prototype can be tailored to a specific application by adjusting the laydown pattern to increase the functionality of the prototype, and that these properties can be predicted by composite theory.
We studied the feasibility of creating new tissue engineered tendons, using bovine tendon fibroblasts (tenocytes) attached to synthetic biodegradable polymer scaffolds in athymic mice. Calffore- and hind-limbs were obtained from a local slaughterhouse within 6 hours of sacrifice. Tenocytes were isolated from the calf tendons. Cells were seeded onto an array of fibers composed of polymer (PGA) configured either as a random mesh of fibers, or as an array of parallel fibers. Fifty cell-polymer constructs were implanted subcutaneously in athymic mice and harvested at 3, 6, 8, 10 and 12 weeks. Grossly, all excised specimens resembled the tendons from which the cells had been isolated. Histologic sections stained with hematoxylin and eosin (H&E) and Masson's trichrome showed cells arranged longitudinally within parallel collagen fibers in the periphery. Centrally, collagen fibers were more randomly arranged, although they seemed to attain a parallel arrangement of cells and fibers over time. By 10 weeks, specimens showed very similar histologic characteristics to normal tendon. Histologically, 12-week samples were virtually identical to normal tendon. When longitudinal polymer fibers seeded with cell had been implanted, the collagen fibers seen in the neo-tendons became organized at an earlier interval of time. Biomechanical tests demonstrated linear increase in tensile strength of the neo-tendons over time. Eight-week specimens showed 30% the tensile strength of normal tendon samples of similar size. By 12 weeks, tensile strength was already 57% that of normal bovine tendon.
A standard protocol is proposed which has been used to study comparatively the degradation mechanism of bioresorbable poly(-hydroxy acids) with respect to macromolecular structural characteristics and solid-state morphologies. As a first approach, the hydrolytic degradation of poly(dl-lactic acid) (PLA50) parallelepipedic specimens (15 mm10 mm2 mm), processed by compression moulding and machining, was investigated in two aqueous media: iso-osmolar saline and pH 7.4 phosphate buffer. Various techniques (namely weighing, size-exclusion chromatography (SEC), potentiometry, cryometry and enzymatic assay) have been applied to these specimens in order to monitor the degradation. Data show conclusively that the degradation of massive PLA50 specimens proceeds more rapidly in the centre than at the surface. This feature has been related to the formation of an outer layer of slowly degrading polymer, which is caused by surface phenomena and entraps degrading macromolecules. Only oligomers can diffuse and dissolve in the surrounding media. Accordingly, the number of carboxylic groups present in the inner part of the degrading specimens becomes larger than at the surface and accelerates ester bond cleavage. The resultant autocatalytic mechanism explains well the fact that partially degraded PLA50 exhibits bimodal SEC chromatograms although this polymer is amorphous.
The field of biodegradable polymers is a fast growing area of polymer science because of the interest of such compounds for temporary surgical and pharmacological applications. Aliphatic polyesters constitute the most attractive family among which poly(-hydroxy acids) have been extensively studied. In the past two decades, several excellent reviews have been published to present the general properties of aliphatic polyesters. The aim of this paper is to complete the information collected so far with a special attention to the complex phenomena of biodegradability and biocompatibility. Indeed, the degradation of a polymer leads to the delivery of low molecular weight degradation by-products whose effects on the host body have to be considered. The consequences of the absence of standard terminology are first discussed with respect to words such as biodegradable and bioresorbable. Poly(-hydroxy acids) derived from lactic and glycolic acids are then introduced in order to make easier the critical discussions of the following problems from literature data: biocompatibility, biodegradability, bioresorbability, mechanism of hydrolysis (enzymaticvs simple chemistry), polymodality of molecular weight distributions during degradation and the effects of the presence of oligomers. Finally, some specific comments are made on other aliphatic polyesters such as poly(hydroxy butyrate) and poly(-malic acid).
In order to assess the effects of morphology on the degradation characteristics of high-molecular weight poly(l-lactic acid) (PLA100), specimens of similar sizes were processed by compression moulding and made either amorphous by quenching (PLA100A) or semicrystalline by annealing (PLA100C). PLA100A specimens were allowed to age in iso-osmolar saline and pH 7.4 phosphate buffer at 37 C for periods up to 2 years, whereas PLA100C specimens were studied in the buffer only. Various techniques were used to monitor comparatively the effects of morphology on the mechanism of hydrolytic degradation for these two types of PLA100 specimens: weighing, enzymatic assay, potentiometry, viscoelasticimetry, size-exclusive chromatography, (SEC), X-ray scattering and differential scanning calorimetry. As in the case of non-crystallizable members of the poly(-hydroxy acid) family, degradation was found to proceed more rapidly in the centre than at the surface for both PLA100A and PLA100C specimens. However, the observed multimodal SEC chromatograms have been assigned primarily to differences of degradation rates in amorphous and crystalline domains, regardless of the initial morphology. Indeed, it was found that initially amorphous PLA100A crystallized as degradation proceeded. Furthermore, PLA100A specimens retained mechanical properties for longer than semicrystalline PLA100C specimens, probably because of the sensitivity of the latter to stress and solvent microcracking. When the integrity of the polymer mass was lost, the residual crystalline matter, initially present or formed during degradation, appeared to be very resistant and was still present in a powdered form after 2 years. It is concluded that the morphology is a critical factor for the degradation of PLA100 and that the degradation of bioresorbable devices derived from this polymer should depend very strongly on both the thermal history and the initial crystallinity. The effects of the morphology do not depend significantly on the nature of the ageing medium, provided that the ionic strength is the same.
Demineralized bone powder (DBP) implanted in vivo induces endochondral bone formation (osteoinduction). Connective tissue cells migrate to the powders and they begin to produce cartilage matrix. Subsequently, vascularization is stimulated and the cartilage is replaced by bone and marrow. Demineralized bone implants have been used clinically for a variety of osseous reconstructive applications. We designed a novel three-dimensional (3-D) device to examine the mechanism of chondroinduction in vitro. Normal human dermal fibroblasts (hDFs) were cultured in 3-D collagen sponges with and without DBP. The cells migrated through the collagen lattice and they attached to and spread onto particles of demineralized bone. Cells vicinal to the DBP produced cartilage matrix proteoglycans. Induced cells expressed cartilage-specific gene products, type II collagen and aggrecan. Control hDFs did not produce cartilage matrix when cultured in plain collagen sponges. This experimental system has the potential to reveal mechanisms of gene activation and other early steps in postnatal chondro/osteoinduction. Further, these results suggest that it may be possible to engineer human cartilage for transplantation by culturing autogenous dermal fibroblasts with a chondroinductive agent.
A particulate-leaching method was developed to prepare highly porous biodegradable polymer membranes. It involves the casting of polymer/salt composite membranes followed by the dissolution of the salt. Poly(l-lactic acid) porous membranes of controlled porosity, surface/volume ratio, and crystallinity were prepared with sodium chloride, sodium tartrate or sodium citrate sieved particles. For salt weight fractions of 50 and 60 wt%, asymmetric membranes were formed, independent of salt particle size. When 70–90 wt% salt was used, the membranes were homogeneous with interconnected pores. The membrane properties were independent of the salt type and were only related to the salt weight fraction and particle size. The porosity increased with the salt weight fraction, and the median pore diameter increased as the salt particle size increased. The polymer/salt composite membranes could be quenched or annealed to yield amorphous or semicrystalline foams with desired crystallinity. All foams were 99.9 wt% salt free and had porosities as high as 0.93 and median pore diameters up to 150 μm.
The rapid expansion of supercritical solutions (RESS) is a new and promising method of particle formation. The distinguishing features of this process are the fast attainment of uniform conditions and of high supersaturations in the carrier fluid, which favor the formation of small, monodisperse particles. The technique has been applied to inorganic, organic, pharmaceutical, and polymeric materials. RESS can be used to comminute shock-sensitive solids, to produce intimate mixtures of amorphous materials, to form polymeric microspheres, and to deposit thin films. In this paper, we discuss the fundamentals, experimental methods, applications, and available results from studies of particle formation with supercritical solutions.
Three-dimensional printing (3DP) is used to create resorbable devices with complex concentration profiles within the device. 3DP is an example of a solid free-form fabrication method where both the macro- and microstructure of the device can be controlled since objects are built by addition of very small amounts of matter. Application of this novel technology for fabrication of polymeric drug delivery systems is described in this article. The drug concentration profile is first specified in a computer model of the device which is then built using the 3DP process. Complex drug delivery regimes can be created in this way, such as the release of multiple drugs or multiphasic release of a single drug. This study demonstrates several simple examples of such devices and several construction methods that can be used to control the release of the drugs. Two dyes are used as model drugs in a matrix of biocompatible polymers. The dye release rate and release time are controlled by either specifying the position of the dye within the device or by controlling the local composition and microstructure with the 3DP process. The mechanism of resorption can also be controlled by manipulating the composition and microstructure of the device during construction. Polyethylene oxide and polycaprolactone were selected as matrix materials and methylene blue and alizarin yellow were used as drug models. Devices with erosion and diffusion controls are described in this report. Spectrophotometric analysis of dye release yielded reproducible results.
An emulsion freeze-drying method for processing porous biodegradable copolymers of polylactic and polyglycolic acid (PLGA) scaffolds was developed. Scaffold porosity and pore sizes were measured using mercury porosimetry. Foams with porosity in the range 91–95%, median pore diameters ranging from 13 to 35 μm (with larger pore diameters greater than 200 μm), and specific pore area in the range 58–102 m2 g−1 were made by varying processing parameters such as water volume fraction, polymer weight percentage and polymer molecular weight. These scaffolds may find applications as structures that facilitate either tissue regeneration or repair during reconstructive operations.
Three Dimensional Printing is a process for the manufacture of tooling and functional prototype parts directly from computer models. Three Dimensional Printing functions by the deposition of powdered material in layers and the selective binding of the powder by “ink-jet” printing of a binder material. Following the sequential application of layers, the unbound powder is removed, resulting in a complex three-dimensional part. The process may be applied to the production of metal, ceramic, and metal/ceramic composite parts.An experiment employing continuous-jet ink-jet printing technology has produced a three-dimensional part comprising eight intersecting planes spaced 0.375 inches apart. Future research will be directed toward the direct fabrication of cores and shells for metal casting, and toward the fabrication of porous ceramic preforms for metal-ceramic composite parts.
Articular cartilage can tolerate a tremendous amount of intensive and repetitive physical stress. However, it manifests a striking inability to heal even the most minor injury. Both the remarkable functional characteristics and the healing limitations reflect the intricacies of its structure and biology. Cartilage is composed of chondrocytes embedded within an extracellular matrix of collagens, proteoglycans, and noncollagenous proteins. Together, these substances maintain the proper amount of water within the matrix, which confers its unique mechanical properties. The structure and composition of articular cartilage varies three-dimensionally, according to its distance from the surface and in relation to the distance from the cells. The stringent structural and biological requirements imply that any tissue capable of successful repair or replacement of damaged articular cartilage should be similarly constituted. The response of cartilage to injury differs from that of other tissues because of its avascularity, the immobility of chondrocytes, and the limited ability of mature chondrocytes to proliferate and alter their synthetic patterns. Therapeutic efforts have focused on bringing in new cells capable of chondrogenesis, and facilitating access to the vascular system. This review presents the basic science background and clinical experience with many of these methods and information on synthetic implants and biological adhesives. Although there are many exciting avenues of study that warrant enthusiasm, many questions remain. These issues need to be addressed by careful basic science investigations and both short- and long-term clinical trials using controlled, prospective, randomized study design.
Chondrocytes were cultured from cartilage harvested from the iliac apophysis and knee joints of New Zealand White (NZW) rabbits. An experimental model for growth arrest was created by excising the medial half of the proximal growth plate of the tibia of 6-week-old NZW rabbits. The cultured chondrocytes were embedded in agarose and transferred into the growth-plate defect after excision of the physis. Transfer also was performed after excision of the bony bridge in established growth arrest. In both cases, growth arrest with angular deformation of the tibia was prevented. Histologic studies confirmed the viability of the chondrocytes in the new host physis.
Biodegradable implants that release growth factors or other bioactive agents in a controlled manner are investigated to enhance the repair of musculoskeletal tissues. In this study, the in vitro release characteristics and mechanical properties of a 50:50 polylactic acid/polyglycolic acid two phase implant were examined over a 6-week period under no-load conditions or under a cyclic compressive load, such as that experienced when walking slowly during rehabilitation. The results demonstrated that a cyclic compressive load significantly slows the decrease of molecular chain size during the first week, significantly increases protein release for the first 2-3 weeks, and significantly stiffens the implant for the first 3 weeks. It was also shown that protein release is initially high and steadily decreases with time until the molecular weight declines to about 20% of its original value (approximately 4 weeks). Once this threshold is reached, increased protein release, surface deformation, and mass loss occurs. This study also showed that dynamic loading and the environment in which an implant is placed affect its biodegradation. Therefore, it may be essential that in vitro degradation studies of these or similar implants include a dynamic functional environment.
Highly pure, recombinant human osteoinductive proteins make it possible to consider programmable osteoneogenesis. Until recently, it was believed that a bioresorbable excipient or physiologic solution would suffice to transport osteoinductive agents from source to wound. After considering surgical requirements, particular bone wound circumstances, scarcity of collateral circulation, phenotype plasticity of mesenchymal progenitor cells, and the morphogens' pleiotrophic effects, it becomes clear that the issue of controlled, programmable osteoneogenesis is a more complicated proposition than can be addressed solely by application of osteoinductive protein. The essential characteristics of a manufactured bone graft substitute (BGS) device are dictated by demands placed on such a device by the surgeons who will employ them and the cells that will occupy them. This review outlines a design process for BGS devices that (1) begins by surveying BGS requirements gathered from the literature from 1991 to 1995, (2) briefly reviews recent in vitro studies of rhBMP-2 and OP- 1, (3) describes commonly encountered circumstances of recipient wound beds, (4) describes behaviors of mesenchymal cells involved in connective tissue repair and regeneration, and (5) concludes with a rationale for design of an osteoinductive bone graft substitute. Emerging from this process is a composite device consisting of a bioresorbable structural polymer, a filamentous velour of hyaluronan (HY), and an osteoinductive protein. The structural polymer, D,D-L,L-polylactic acid, fabricated in the architecture of cancellous bone, is capable of maintaining its structural and architectural properties after being thoroughly saturated with water. Within its interstices is located a filamentous velour of hyaluronan which, when fully hydrated, becomes a viscoelastic gel. It is anticipated that the osteoinductive protein will either be carried on the dried hyaluronic acid velour or in solution via the viscoelastic HY gel.
Tissue engineering is moving rapidly from potential to accepted medical practice. Use of human diploid fibroblast cells to form three-dimensional dermal replacement tissue is described. The cell source of these products is fully tested and the products may be frozen and stored prior to use. A summary of pilot clinical trials for Dermagraft()-Transitional Covering and Dermagraft()-Ulcer show the feasibility of this approach. A development program for cartilage tissue has resulted in both reconstructive and orthopedic applications that have been demonstrated in preclinical animal studies. Cardiovascular applications to prosthetic biological heart valve constructs are also discussed.
Highly porous biodegradable foams with controlled release function were fabricated by a phase separation technique. This technique involved inducing phase changes in a homogeneous solution of polymers with naphthalene or phenol used as solvents. A variety of foams with pore sizes ranging from 20 to 500 microm were made of poly(L-lactic acid) (PLLA), poly(bisphenol A-phenylphosphonate (BPA/PP), and its copolymer with poly[bis(2-ethoxy)- hydrophosphonic terephthalate] (PP/PPET). Controlled delivery capability was demonstrated by studying the release of sulforhodamine B and alkaline phosphatase (AP) from these highly porous structures. After an initial burst, AP was released from BPA/PP and PLLA foams at a near steady rate of 0.32 +/- 0.04 and 0.49 +/- 0.13 mg/day/g foam, respectively. These foams were intended for use as cell transplantation devices and tissue grafts such as synthetic bone grafts. Hydroxyapatite (HA) was added into the foams in an attempt to enhance interaction of these foams with bone. This composite was analyzed by energy dispersive spectroscopy, differential scanning calorimetry, and thermomechanical analysis. Since phosphates are known to have good affinity to calcium, poly(phosphoester) foams were treated with 1M calcium chloride solution in an attempt to study the possible interaction of the degrading poly(phosphoester) with calcium. After three weeks in 1 M calcium chloride solution, the complex modulus of the poly(phosphoester) foams changed from 40 to 1948 kPa, with a concurrent decrease in loss tangent from 0.349 to 0.170.
Tissue engineering has shown great promise for creating biological alternatives for implants. In this approach, scaffolding plays a pivotal role. Hydroxyapatite mimics the natural bone mineral and has shown good bone-bonding properties. This paper describes the preparation and morphologies of three-dimensional porous composites from poly( L -lactic acid) (PLLA) or poly( D,L -lactic acid-co-glycolic acid) (PLGA) solution and hydroxyapatite (HAP). A thermally induced phase separation technique was used to create the highly porous composite scaffolds for bone-tissue engineering. Freeze drying of the phase-separated polymer/HAP/solvent mixtures produced hard and tough foams with a co-continuous structure of interconnected pores and a polymer/HAP composite skeleton. The microstructure of the pores and the walls was controlled by varying the polymer concentration, HAP content, quenching temperature, polymer, and solvent utilized. The porosity increased with decreasing polymer concentration and HAP content. Foams with porosity as high as 95% were achieved. Pore sizes ranging from several microns to a few hundred microns were obtained. The composite foams showed a significant improvement in mechanical properties over pure polymer foams. They are promising scaffolds for bone-tissue engineering. © 1999 John Wiley & Sons, Inc. J Biomed Mater Res, 44, 446–455, 1999. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/34413/1/11_ftp.pdf
This paper reviews our research in developing novel matrices for cell transplantation using bioresorbable polymers. We focus on applications to liver and cartilage as paradigms for regeneration of metabolic and structural tissue, but review the approach in the context of cell transplantation as a whole. Important engineering issues in the design of successful devices are the surface chemistry and surface microstructure, which influence the ability of the cells to attach, grow, and function normally; the porosity and macroscopic dimensions, which affect the transport of nutrients to the implanted cells; the shape, which may be necessary for proper function in tissues like cartilage; and the choice of implantation site, which may be dictated by the total mass of the implant and which may influence the dimensions of the device by the available vascularity. Studies show that both liver and cartilage cells can be transplanted in small animals using this approach.
This article provides a concise review of bone induction. Bone induction by demineralized bone matrix is a multistep cascade. The purification and elucidation of the chemistry of osteogens will improve bone grafting methods.
Patients with fractures of the zygomatic bone were treated with high molecular weight poly(L-lactic) acid (PLLA) bone plates and screws. Three years after implantation four patients returned to our department with a swelling at the site of implantation. At the recall of the remaining patients we found an identical type of swelling after the same implantation period. To investigate the nature of the tissue reaction, eight patients were reoperated for the removal of the swelling. The implantation period of the PLLA material varied from 3.3 to 5.7 years. Microscopic evaluation and molecular weight measurements were performed. The excised material showed remnants of degraded PLLA material surrounded by a dense fibrous capsule. Ultrastructural investigation showed crystal-like PLLA material internalized by various cells. The results of this investigation suggest that the PLLA material slowly degrades into particles with a high crystallinity. The intra- and extracellular degradation rate of these particles is very low. After 5.7 years of implantation, these particles were still not fully resorbed.
In a previous article in the Journal of Oral and Maxillofacial Surgery, the initial results of treating 10 patients with solitary, unstable, displaced zygomatic fractures using resorbable poly(L-lactide) (PLLA) plates and screws was reported (Bos et al, 1987). This article describes the long-term results in these patients. Three years postoperatively, four patients returned because they were concerned about an intermittent swelling at the site of implantation. The remaining patients were recalled after the same postoperative period. All patients were examined clinically, and six patients were operated on again for evaluation of the swelling and to investigate the nature of the tissue reaction. The explanted material showed remnants of degraded PLLA surrounded by a dense fibrous capsule. The swelling was classified as a nonspecific foreign body reaction to the degraded PLLA material. Ultrastructural investigation of the degraded material showed an internalization of crystal-like PLLA material in the cytoplasm of various cells.
The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in human health care.
A new field, tissue engineering, applies the principles of biology and engineering to the development of functional substitutes
for damaged tissue. This article discusses the foundations and challenges of this interdisciplinary field and its attempts
to provide solutions to tissue creation and repair.
A novel processing technique is reported to construct three-dimensional biodegradable polymer foams with precise anatomical shapes. The technique involved the lamination of highly-porous membranes of porosities up to 90%. Implants with specific shapes were prepared made of poly(L-lactic acid) and copolymers of poly(DL-lactic-co-glycolic acid) to evaluate feasibility. The biomaterials produced have pore morphologies similar to those of the constituent membranes. The pores of adjacent layers of laminated devices are interconnected, resulting in continuous pore structures. The compressive creep behaviour of multilayered devices is also similar to that of the individual layers. Recent discoveries from our group and others that organs and tissues can be regenerated and reconstructed, using cells cultured on synthetic biodegradable polymers, renders this method useful in creating polymer-cell graft for use in cell transplantation.
The resorbable polymers polyglycolic acid (PGA) and polylactic acid (PLA) are gaining increasing importance in tissue engineering and cell transplantation. The present investigation was focused on the biocompatibility and cell retaining behavior of PGA/poly-L-lactide (PLLA) (90/10) and PLLA nonwoven structures for the in vitro development of chondrocyte-polymer constructs. The effect of the relevant monomers to chondrocytes was analyzed. Type II collagen and poly-L-lysine were compared to improve loading of PGA/PLLA and PLLA polymer nonwovens with chondrocytes. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zoliumbrom ide (MTT) test was applied for quantification. At concentrations above 2 mg/mL, glycolic acid was more cytotoxic than lactic acid. As shown by pH equilibration, the cytotoxic effect is not due merely to the acidity of the alpha-hydroxy acids. Regarding the degradation products, glycolic acid, and L(+) lactic acid, nonwovens of PLLA are more biocompatible with chondrocytes than nonwovens of polyglycolide. Collagen type II and poly-L-lysine generally improved cell seeding on resorbable polymers in tissue engineering; however, their efficiency varies depending on the type of fiber structure.
A novel method was developed to produce highly porous sponges for potential use in tissue engineering, without the use of organic solvents. Highly porous sponges of biodegradable polymers are frequently utilized in tissue engineering both to transplant cells or growth factors, and to serve as a template for tissue regeneration. The processes utilized to fabricate sponges typically use organic solvents, but organic residues remaining in the sponges may be harmful to adherent cells, protein growth factors or nearby tissues. This report describes a technique to fabricate macroporous sponges from synthetic biodegradable polymers using high pressure carbon dioxide processing at room temperature. Solid discs of poly (D,L-lactic-co-glycolic acid) were saturated with CO2 by exposure to high pressure CO2 gas (5.5 MPa) for 72 h at room temperature. The solubility of the gas in the polymer was then rapidly decreased by reducing the CO2 gas pressure to atmospheric levels. This created a thermodynamic instability for the CO2 dissolved in the polymer discs, and resulted in the nucleation and growth of gas cells within the polymer matrix. Polymer sponges with large pores (approximately 100 microns) and porosities of up to 93% could be fabricated with this technique. The porosity of the sponges could be controlled by the perform production technique, and mixing crystalline and amorphous polymers. Fibre-reinforced foams could also be produced by placing polymer fibres within the polymer matrix before CO2 gas processing.
Potential of thermally induced phase separation as a porogen technique has been studied in an effort to produce a surgical implant suitable for cell transplantation. Emphasis has been placed on the liquid-liquid phase separation of solutions of amorphous poly DL-lactide and semicrystalline poly L-lactide in an 87/13 dioxane/water mixture. The related temperature/composition phase diagrams have been set up by turbidimetry, and the possible occurrence of a gel has been discussed. Freeze-drying of some phase-separated polylactide solutions can produce flexible and tough foams with an isotropic morphology. Interconnected pores of 1-10 microns in diameter are expected to result from the spinodal decomposition of the polylactide solutions with formation of co-continuous phases. Thermodynamics of the polymer/solvent pair has a decisive effect on the final macroporous foams, as shown by the dependence of their porosity, density, porous morphology, and mechanical behavior on molecular weight and crystallinity of polylactide and concentration of the original solutions. On the basis of the foam characteristics, potential of the liquid-liquid phase separation (spinodal decomposition) has been compared with the solid/liquid phase separation (solvent crystallization) as a porogen technique.