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Regenerative medicine is becoming a rapidly evolving technique in today’s biomedical progress scenario. Scientists around the world suggest the use of naturally synthesized biomaterials to repair and heal damaged cells. Hydroxyapatite (HAp) has the potential to replace drugs in biomedical engineering and regenerative drugs. HAp is easily biodegrada...
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... (Figure 2) is used as the main ingredient in many drug-delivery systems and biomaterials such as ointments and dressings. Its basic physical and structural properties, along with low immunogenicity and natural turnover, are the key to its biocompatibility and efficacy. ...
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... are plant secondary metabolites belonging to a large group of polyphenolic compounds. Flavonoids' carbon framework is characterized by a C6-C3-C6 skeleton exhibiting the structure of a chromane or that of a chromene formed by a fused benzene ring (A), the 3,4-dihydro-2H-pyran, or the pyran (ring C) and a phenyl group (ring B) substituted on ring C (Figure 20) [320,321]. Materials 2021, 14, x FOR PEER REVIEW 35 of 57 was poured drop by drop into the HAp/coll/paraffin scaffold to completely fill the area between the paraffin microspheres. ...
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... are plant secondary metabolites belonging to a large group of polyphenolic compounds. Flavonoids' carbon framework is characterized by a C6-C3-C6 skeleton exhibiting the structure of a chromane or that of a chromene formed by a fused benzene ring (A), the 3,4-dihydro-2H-pyran, or the pyran (ring C) and a phenyl group (ring B) substituted on ring C (Figure 20) [320,321]. Due to structural differences, such as oxidation and hydroxylation levels, as well as substitution of the C ring, flavonoids can be divided into a few major classes, including flavanols, flavanones, flavones, flavonols, anthocyanidines, isoflavonoids (compounds with a 3-phenyl-4H-chromen-4-one), and neoflavonoids (compounds with a 4-phenyl-2H-chromen-2-one) [322][323][324]. ...
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... research was performed by Song et al. [381]. Their paper describes composite sponges prepared by lyophilization and composed of collagen isolated from duck's feet, hydroxyapatite, and quercetin (Qt) (Figure 22), a compound belonging to the flavonol subgroup. The SEM analysis of the morphology of such obtained materials revealed their uniform 3D structure with well-oriented pores. ...
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... research was performed by Song et al. [381]. Their paper describes composite sponges prepared by lyophilization and composed of collagen isolated from duck's feet, hydroxyapatite, and quercetin (Qt) (Figure 22), a compound belonging to the flavonol subgroup. The SEM analysis of the morphology of such obtained materials revealed their uniform 3D structure with well-oriented pores. ...
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... flavonoid tested by the same research group as an active ingredient of HAp/Coll sponges was silymarin (Sm) (Figure 23) [382]. The Sm-containing HAp/Coll sponges were prepared by freeze-drying. ...
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... flavonoid tested by the same research group as an active ingredient of HAp/Coll sponges was silymarin (Sm) (Figure 23) [382]. The Sm-containing HAp/Coll sponges were prepared by freeze-drying. ...
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... core-shell multicomponent materials mimicking the structure of bone were proposed by Zhao et al. [383]. The authors obtained material composed of HAp/Coll/polycaprolactone (PCL) electrospun shell and a freeze-dried core consisted of a collagen with icariin (Ic) (Figure 24) loaded chitosan microspheres. The core-shell materials were cross-linked by genipin. ...
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... core-shell multicomponent materials mimicking the structure of bone were proposed by Zhao et al. [383]. The authors obtained material composed of HAp/Coll/poly caprolactone (PCL) electrospun shell and a freeze-dried core consisted of a collagen with icariin (Ic) (Figure 24) loaded chitosan microspheres. The core-shell materials were crosslinked by genipin. ...
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... Since biocomposites of CaPO4 with collagen were found to be able to form bioconjugates (bioconjugation is a chemical strategy to form a stable covalent link between two molecules, at least one of which is a biomolecule [784]), they are beneficial for the delivery of drugs, growth factors, and other biomolecules [610,720,765,[785][786][787]. Namely, 5 weeks after implantation, HA/collagen-alginate (20 µL) supplemented with rhBMP-2 (100 µg/mL, 15 µL) demonstrated osteogenesis along the implant without the material deforming much [610]. ...
... Furthermore, a bilayer collagen/β-TCP implant supplemented with cartilage-inducing growth factors was developed for the repair of osteochondral defects in the trochlear groove in miniature pigs [785]. More details on this topic can be found in a recent review [786]. ...
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.
... The most popular inorganic material in regenerative medicine is hydroxyapatite (HA, general formula: Ca 5 (PO 4 ) 3 OH), a calcium phosphate mimicking the composition of human mineralized tissues, so that it shows excellent biocompatibility, bioactivity, osteoinductivity, biodegradability, and non-immunogenic behavior [72][73][74][75][76][77][78]. For this reason, HA is since decades considered as the reference material for application in bone tissue engineering, more recently also in soft tissue regeneration with antibacterial capability, and also explored as vehicles for drug delivery, thanks to its ability to link a variety of drugs and biological molecules [79][80][81][82][83][84][85]. ...
... The type and concentration of iron ions inside the HA lattice play a crucial role in influencing the properties of magnetic HA [82]. For instance, it has been reported that the crystallite size and crystallinity of HA particles are reduced by increasing the Fe ions concentration, where the magnetic behavior shifted from diamagnetic to superparamagnetic [74][75][76][77][78][79][80][81][82][83]. ...
This review focuses on the latest advancements in magnetic hydroxyapatite (mHA) nanoparticles and their potential applications in nanomedicine and regenerative medicine. mHA nanoparticles have gained significant interest over the last few years for their great potential, offering advanced multi-therapeutic strategies because of their biocompatibility, bioactivity, and unique physicochemical features, enabling on-demand activation and control. The most relevant synthetic methods to obtain magnetic apatite-based materials, either in the form of iron-doped HA nanoparticles showing intrinsic magnetic properties or composite/hybrid compounds between HA and superparamagnetic metal oxide nanoparticles, are described as highlighting structure-property correlations. Following this, this review discusses the application of various magnetic hydroxyapatite nanomaterials in bone regeneration and nanomedicine. Finally, novel perspectives are investigated with respect to the ability of mHA nanoparticles to improve nanocarriers with homogeneous structures to promote multifunctional biological applications, such as cell stimulation and instruction, antimicrobial activity, and drug release with on-demand triggering.
... The natural chemistry of pristine CNTs is that they bundle together and become inseparable in solutions. Yet the success of CNT application in any technology within the wastewater treatment sphere is strongly dependent on the capability of disbanding them into individual nanotubes, thus making them homogenous and stable suspensions [30]. Hence, CNT surface modification engineering is crucial for advanced CNT surface properties. ...
... For the current work, CNT modification was done by soaking a specific amount of CNTs in a solution of concentrated sulfuric acid (99%) and nitric acid (65%) at a volume ration of 1:2, respectively for 24 hours. The liquidphase oxidation of CNTs using an acid containing oxygen molecules, results in the attachment of functional groups such as carboxylic and hydroxyl groups on the CNT surface which are essential for contaminant removal in the aqueous environment [30]. Thereafter, the acid functionalized CNTs were rinsed with deionized water until a pH of 7 was achieved for the filtrate. ...
... At the core of tissue engineering lies the development of biocompatible and functional biomaterials that can facilitate cell growth, differentiation, and integration with the host tissue. One such biomaterial that has gained significant attention in recent years is hydroxyapatite (HAp), a calcium phosphate mineral with unique properties that make it highly desirable for various tissue engineering applications (Sobczak-Kupiec et al. 2021). Marine-derived hydroxyapatite, extracted from abundant and renewable sources such as fish bones, shells, and coral skeletons, offers an alternative to synthetic HAp and presents several advantages in terms of biocompatibility, sustainability, and cost-effectiveness. ...
... HAp can readily bond with living tissue, promoting cell adhesion, proliferation, and differentiation. HAp can facilitate bone growth along its surface, providing a scaffold for bone regeneration (Sobczak-Kupiec et al. 2021 ...
... The peak at 866.15/cm is believed to be due to the non-apatite environment's out-of-plane bending mode (ν 2 ) 45,49 , which confirms the carbonation of HA-700 samples 31 . The CO 2− 3 ions present in the lattice structure of HA-700 are known to be medically preferred because they enhance its biodegradability [2][3][4][5][6]12,13,17,19,22,24,36 . Adsorbed H 2 O was conformed from the broad band centered at 3450.77/cm and an intense band at 1639.98/cm for HA-700 and at 3452.48/cm and 1639.90/cm for HA-1000 calcined samples ( Fig. 4B and C), which are always present in bone-derived biological apatite 32,48,50 . ...
Hydroxyapatite (HA) can be used in odontology and orthopedic grafts to restore damaged bone due to its stable chemical characteristics, composition, and crystal structural affinity for human bone. A three-step hydrothermal method was used for the extraction of biogenic calcined HA from the buffalo waste bones at 700 °C (HA-700) and 1000 °C (HA-1000). Extracts were analyzed by thermogravimetric analysis, differential scanning calorimetry, X-ray fluorescence, X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and in vivo examination of HA xenografts for femoral lesions in experimental rats. Crystallinity, purity, and morphology patterns showed that the HA main phase purity was 84.68% for HA-700 and 88.99% for HA-1000. Spherical HA nanoparticles were present for calcined HA-700 samples in the range 57–423 nm. Rats with critical bone lesions of
3 mm in diameter in the left femur treated with calcined HA-700 nanoparticles healed significantly (p < 0.001) faster than rats treated with HA-1000 or negative controls. These findings showed that spherical biogenic HA-700 NPs with a bud-like structure have the potential to stimulate both osteoconduction and bone remodeling, leading to greater bone formation potential in vivo. Thus, the calcined biogenic HA generated from buffalo waste bones may be a practical tool for biomedical applications.
... Coatings 2023, 13, 1681 2 of 15 HA, being one of the main components of human bones, is biocompatible, bioactive, and thermodynamically stable in body fluid environments [19,20]. It also actively takes part in essential bone regeneration processes by osteogenic stimulation through the release of Ca 2+ , PO 4− , and OH − ions when in contact with blood plasma [21]. Coating the metal surface with HA offers numerous solutions to problems such as metal ion release from the metal surface, foreign body inflammation, and bone cell repair. ...
... Coating the metal surface with HA offers numerous solutions to problems such as metal ion release from the metal surface, foreign body inflammation, and bone cell repair. Research progress has shown that crystalline HA is the most active constituent in human bones and is more stable in human body fluids that contain a variety of dissolving ions [15,21]. Among conventional coating methods, pulsed laser deposition (PLD) has been successful in producing crystalline HA coatings with applicable adhesion strength [22][23][24]. ...
In this study, the effects of substrate temperature and ablation wavelength/mechanism on the structural, mechanical, and bioactivity properties of hydroxyapatite (HA) coatings were investigated. HA coatings were deposited on both Si(100) and Ti6Al4V surfaces. Substrate temperature varied from room temperature to 800 °C. Depositions were performed in Ar/H2O and vacuum environments. X-ray diffraction, scanning electron microscopy, and atomic force microscopy techniques were used to analyze structural and morphological variations. The adherence of coatings to the substrates was assessed by the pull-out method. The obtained data indicated that with the temperature increase, the coatings steadily crystallized. However, temperatures above 700 °C adversely affected protein adsorption and adhesion properties. Similar trends were confirmed via pull-out testing, protein adsorption, and cell proliferation tests. The ablation mechanism was also proven to play an important role in the deposition process. Overall, this study provides further evidence that crystallinity is a vital factor in the functionality of the coatings and depends on the deposition conditions. However, all measurements directly indicated that beyond 700 °C, the morpho-structural, mechanical, and bioactivity properties degrade.
... One of the most promising biomaterials for medical applications is hydroxyapatite (HAp) because it is the natural mineral phase of bone and has shown to promote cell viability and enhance collagen deposition [13,14]. HAp, derived from biogenic sources, has been particularly highlighted because it promotes biological interactions and reactions and has biocompatibility and biodegradability properties. ...
... Because HAp is fragile and brittle, it is often used as implant coatings using deposition methods such as the micro-arc oxidation method or plasma electrolytic oxidation [16,17]. Regarding scaffold architecture, porosity, and pore interconnectivity are of great importance to ensure cell settlement, tissue growth, vascularization, efficient nutrient penetration, and waste removal [12,13]. Considering the above, natural scaffolds from biogenic sources represent an interesting alternative for bone tissue engineering since they can mimic the properties of BTE. ...
... Tropocollagen consists of a right-handed triple helix of three parallel left-handed polyproline II-type chains of equal length containing the repeating amino acid sequence [Gly − X − Y] n , with the positions X and Y being predominantly occupied by proline and hydroxyproline. Adapted and reproduced from [163]. ...
Bone tissue engineering (BTE) aims to improve the healing of bone fractures using scaffolds that mimic the native extracellular matrix. For successful bone regeneration, scaffolds should promote simultaneous bone tissue formation and blood vessel growth for nutrient and waste exchange. However, a significant challenge in regenerative medicine remains the development of grafts that can be vascularised successfully. Amongst other things, optimisation of physicochemical conditions of scaffolds is key to achieving appropriate angiogenesis in the period immediately following implantation.
Calcium phosphates and collagen scaffolds are two of the most widely studied biomaterials for BTE, due to their close resemblance to inorganic and organic components of bone, respectively, and their bioactivity, tunable biodegradability and the ability to produce tailored architectures. While various strategies exist to enhance vascularisation of these scaffolds in vivo, further in vitro assessment is crucial to understand the relation between physicochemical properties of a biomaterial and its ability to induce angiogenesis. While mono-culture culture studies can provide evidence regarding cell-material interaction of a single cell type, a co-culture procedure is crucial for assessing the complex mechanisms involved in angiogenesis. A co-culture more closely resembles the natural tissue both physically and biologically by stimulating natural intercellular interactions and mimicking the organisation of the in vivo environment. Nevertheless, a co-culture is a complex system requiring optimisation of various parameters including cell types, cell ratio, culture medium and seeding logistics.
Gaining fundamental knowledge of the mechanism behind the bioactivity of biomaterials and understanding the contribution of surface and architectural features to the vascularisation of scaffolds, and the biological response in general, can provide an invaluable basis for future optimisation studies. This review gives an overview of the available literature on scaffolds for BTE, and trends are extracted on the relationship between architectural features, biochemical properties, co-culture parameters and angiogenesis.
... We have found that functionalized chondroitin sulfate with anionic groups (sulfate and carboxyl) serves as the effective calcium ion binding sites, thereby supporting the calcium phosphate nucleation on the surface of ColChCS mod hydrogels [20]. Furthermore, the composites developed in this study were prepared with a widely known bioactive element in the form of hydroxyapatite in MSP-NH 2 -HAp-ALN particles, which is also the main component of the mineral phase of the bone [35,54]. To sum up this aspect of our research, one can conclude that the presence of MSP-NH 2 -HAp-ALN particles in the ColChCS mod matrix supports the mineralization process, which will ensure more effective biointegration in vivo. ...
Alendronate (ALN) is the most commonly prescribed oral nitrogen-containing bisphosphonate for osteoporosis therapy. However, its administration is associated with serious side effects. Therefore, the drug delivery systems (DDS) enabling local administration and localized action of that drug are still of great importance. Herein, a novel multifunctional DDS system based on the hydroxyapatite-decorated mesoporous silica particles (MSP-NH2-HAp-ALN) embedded into collagen/chitosan/chondroitin sulfate hydrogel for simultaneous osteoporosis treatment and bone regeneration is proposed. In such a system, the hydrogel serves as a carrier for the controlled delivery of ALN at the site of implantation, thus limiting potential adverse effects. The involvement of MSP-NH2-HAp-ALN in the crosslinking process was established, as well as the ability of hybrids to be used as injectable systems. We have shown that the attachment of MSP-NH2-HAp-ALN to the polymeric matrix provides a prolonged ALN release (up to 20 days) and minimizes the initial burst effect. It was revealed that obtained composites are effective osteoconductive materials capable of supporting the osteoblast-like cell (MG-63) functions and inhibiting osteoclast-like cell (J7741.A) proliferation in vitro. The purposely selected biomimetic composition of these materials (biopolymer hydrogel enriched with the mineral phase) allows their biointegration (in vitro study in the simulated body fluid) and delivers the desired physicochemical features (mechanical, wettability, swellability). Furthermore, the antibacterial activity of the composites in in vitro experiments was also demonstrated.
... Tissue engineering (TE) deals with the design and production of new tissues to replace the lost parts of human beings [1,2] as a result of traumas, syndromes, accidents, or diseases with identical tissue. To this end, TE promotes complete rehabilitation, which involves the replacement of damaged tissue [3] for the regeneration of functions [4][5][6]. This discipline requires a support, cells, and growth factors and differentiation. ...
Electrospun scaffolds with diameter fibers compared to those in the extracellular matrix were produced with poly(lactic acid) (PLA) and non-denatured collagen from bovine dentin (DCol). DCol was obtained through an improved version of the Longin method by acid erosion of the hydroxyapatite of the roots of teeth from a 2-year-old cattle. The dentin collagen was characterized by energy dispersive X-ray spectroscopy (EDS), and carbon, nitrogen, and oxygen were found to be the main elements of the protein. Infrared analysis revealed the typical bands of collagen at about 3300, 1631, 1539, and 1234 cm ⁻¹ for amides A, I, II, and III, respectively. Calorimetric and infrared analyses also demonstrated that the collagen was non-denatured. With scanning electron microscopy, it was found that the thinnest fibers with a diameter comparable to that of fibers in the extracellular matrix were obtained when dentin collagen and acetic acid (AAc) were added to the solution of PLA in trifluoroethanol (TFE). The scaffolds with the thinnest diameter had also the highest porosity, and we considered that they could be beneficial in the growth of dentin cell. Human placenta-derived mesenchymal stem cells were seeded onto electrospun scaffolds. After 24, 48 and 96 h of culture, cell proliferation was evaluated by two independent strategies. In both assays, it was found that the pl-MSCs were capable of adhering and proliferating in different scaffolds. It was also observed that cell adhesion and proliferation increased significantly in scaffolds containing collagen, although the addition of AAc slightly decreased this effect on all scaffolds.
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