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Hydroxyapatite (HA), a commonly used material for bone repair, can enhance its biological properties through the modulation of its crystallinity. Exploring the variations in physicochemical and biological properties associated with different degrees of crystallinity is crucial for advancing the applications of HA. In this study, stoichiometric nano-apatite precursors were initially synthesized using chemical precipitation. Subsequently, four groups of HA ceramics with varying degrees of crystallinity (24 %, 42 %, 72 %, 100 %) were produced by adjusting the calcination temperature, as confirmed through comprehensive characterizations. A systematic investigation was then conducted to examine the impact of crystallinity on the physicochemical, cytological, and in vivo osteogenic properties of HA ceramics, elucidating the influence of crystallinity on the osteogenic potential of HA. Results indicated that higher crystallinity in HA ceramics enhanced mechanical strength and hardness while reducing surface roughness, hydrophilicity, and protein affinity. Cytological studies revealed that decreased crystallinity led to lower cell proliferation rates but facilitated cell adhesion, spreading, and increased expression of osteogenic genes. Moreover, cell experiments with extracts further supported the significant role of surface properties of HA ceramics in modulating cell behavior. In vivo osteogenic assays demonstrated that reduced crystallinity notably stimulated new bone formation. Overall, by integrating the results of in vitro and in vivo experiments, it can be concluded that reducing the crystallinity of HA ceramics, the biological properties of HA ceramics can be significantly enhanced while maintaining a certain level of mechanical strength, such as HA2 group (42 % crystallinity). This study highlights the substantial impact of crystallinity and surface characteristics of HA ceramics on cell behavior, offering valuable insights and strategies for enhancing and optimizing bone repair materials in future applications. [ABSTRACT FROM AUTHOR]

The demand for novel tissue grafting and regenerative wound care biomaterials is growing as traditional options often fall short in biocompatibility, functional integration with human tissue, associated cost(s), and sustainability. Salmon aquaculture generates significant volumes of waste, offering a sustainable opportunity for biomaterial production, particularly in osteo-conduction/-induction, and de novo clinical/surgical bone regeneration. Henceforth, this study explores re-purposing salmon waste through a standardized pre-treatment process that minimizes the biological waste content, followed by a treatment stage to remove proteins, lipids, and other compounds, resulting in a mineral-rich substrate. Herein, we examined various methods—alkaline hydrolysis, calcination, and NaOH hydrolysis—to better identify and determine the most efficient and effective process for producing bio-functional nano-sized hydroxyapatite. Through comprehensive chemical, physical, and biological assessments, including Raman spectroscopy and X-ray diffraction, we also optimized the extraction process. Our modified and innovative alkaline hydrolysis–calcination method yielded salmon-derived hydroxyapatite with a highly crystalline structure, an optimal Ca/P ratio, and excellent biocompatibility. The attractive nano-scale cellular/tissular properties and favorable molecular characteristics, particularly well-suited for bone repair, are comparable to or even surpass those of synthetic, human, bovine, and porcine hydroxyapatite, positioning it as a promising candidate for use in tissue engineering, wound healing, and regenerative medicine indications. [ABSTRACT FROM AUTHOR]

The development of hydroxyapatite (HAp) and polyether ether ketone (PEEK) biocomposites has been extensively studied for bone repair applications due to the synergistic properties of the involved materials. In this study, we aimed to develop HAp/PEEK biocomposites using high-energy ball milling, with HAp concentrations (20%, 40%, and 60% w/v) in PEEK, to evaluate their physicochemical, mechanical, cytotoxicity, and antimicrobial properties for potential applications in Tissue Engineering (TE). The biocomposites were characterized by structure, morphology, apparent porosity, diametral compression strength, cytotoxicity, and antimicrobial activity. The study results demonstrated that the HAp/PEEK biocomposites were successfully synthesized. The C2 biocomposite, containing 40% HAp, stood out due to the optimal distribution of HAp particles in the PEEK matrix, resulting in higher compression strength (246 MPa) and a homogeneous microstructure. It exhibited antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, with no cytotoxicity observed. These properties make the C2 biocomposite promising for regenerative medicine applications, combining mechanical strength, bioactivity, and biocompatibility. [ABSTRACT FROM AUTHOR]

Structural alteration of synthetic implants aims to achieve better bioactivity, higher cellular response, and regulated degradability, all of which are critical criteria for a biomaterial to serve as a graft in bone regeneration. The aim of this work was to synthesize silicon-substituted hydroxyapatite and test its bioactivity in simulated body fluid (SBF) by proving the use of sodium metasilicate (Na2SiO3.9H2O) as an affordable precursor of silica. Thus, the study evaluated the in vitro bone-bonding capacity of hydroxyapatite (Ca10(PO4)6(OH)2) (HA) substituted with silicate ion (Ca10(PO4)6−x(SiO4)x(OH)2−x; SixHA). The SixHA with x = 0.4 was synthesized by utilizing a wet precipitation method with sodium metasilicate as a low-cost silica alternative for alkoxysilane precursors. The SixHA was then examined for properties such as morphology, elemental composition, phase composition, and the nature of chemical bonds using scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray diffractometry (XRD), and Fourier transformed infrared spectroscopy (FTIR), respectively. An in vitro bioactivity experiment was also carried out by incubating the SixHA in simulated body fluid (SBF) at 36.5 ◦C for 7 and 14 days. The obtained results revealed the substitution of SiO44− for some PO4 3− groups in the hydroxyapatite structure. The SixHA nucleated more apatite crystals on its surface and demonstrated some degradability during the periods of immersion in SBF. The characteristics of the SixHA imply that it could be used as a graft in bone restoration applications, thus signifying that sodium metasilicate could serve as an economic silica source for silicon-substituted hydroxyapatite production. [ABSTRACT FROM AUTHOR]

Simultaneously modulating the inflammatory microenvironment and promoting local bone regeneration is one of the main challenges in treating bone defects. In recent years, osteoimmunology has revealed that the immune system plays an essential regulatory role in bone regeneration and that macrophages are critical components. In this work, a mussel-inspired immunomodulatory and osteoinductive dual-functional hydroxyapatite nano platform (Gold/hydroxyapatite nanocomposites functionalized with polydopamine - PDA@Au-HA) is developed to accelerate bone tissues regeneration by regulating the immune microenvironment. PDA coating endows nanomaterials with the ability to scavenge reactive oxygen species (ROS) and anti-inflammatory properties, and it also exhibits an immunomodulatory ability to inhibit M1 macrophage polarization and activate M2 macrophage secretion of osteogenesis-related cytokines. Most importantly, this nano platform promotes the polarization of M2 macrophages and regulates the crosstalk between macrophages and pre-osteoblast cells to achieve bone regeneration. Au-HA can synergistically promote vascularized bone regeneration through sustained release of Ca and P particles and gold nanoparticles (NPs). This nano platform has a synergistic effect of good compatibility, scavenging of ROS, and anti-inflammatory and immunomodulatory capability to accelerate the bone repair process. Thus, our research offers a possible therapeutic approach by exploring PDA@Au-HA nanocomposites as a bifunctional platform for tissue regeneration. [ABSTRACT FROM AUTHOR]

Nano-hydroxyapatite (n-HA) is the main inorganic component of natural bone, which has been widely used as a reinforcing filler for polymers in bone materials, and it can promote cell adhesion, proliferation, and differentiation. It can also produce interactions between cells and material surfaces through selective protein adsorption and has therefore always been a research hotspot in orthopedic materials. However, n-HA nano-particles are inherently easy to agglomerate and difficult to disperse evenly in the polymer. In addition, there are differences in trace elements between n-HA nano-particles and biological apatite, so the biological activity needs to be improved, and the slow degradation in vivo, which has seriously hindered the application of n-HA in bone fields, is unacceptable. Therefore, the modification of n-HA has been extensively reported in the literature. This article reviewed the physical modification and various chemical modification methods of n-HA in recent years, as well as their modification effects. In particular, various chemical modification methods and their modification effects were reviewed in detail. Finally, a summary and suggestions for the modification of n-HA were proposed, which would provide significant reference for achieving high-performance n-HA in biomedical applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hydroxyapatite is the main inorganic component of bone tissue. The polymer has the structure and function of a biomimetic extracellular matrix. The composites of hydroxyapatite and polymer have been widely studied. OBJECTIVE: To summarize the research status of hydroxyapatite composite polymer materials for bone tissue repair. METHODS: The articles collected in PubMed, Web of Science, CNKI and WanFang databases were searched from January 2010 to April 2023. The Chinese and English search terms were “hydroxyapatite, polymer, composites, degradability, bone defect, bone repair”. Finally, 75 articles were included for review. RESULTS AND CONCLUSION: Polymers often used in composite with hydroxyapatite for bone tissue repair include natural polymers (collagen, chitosan, alginate, serine protein, cellulose, hyaluronic acid,and polyhydroxybutyrate) and synthetic polymers [polylactic acid, polylactic acid-hydroxyacetic acid copolymer, poly(has-lactide), poly(amino acid) and poly(vinyl alcohol)]. The mechanical properties and osteoinductivity of hydroxyapatite/polymer composites were improved compared with pure hydroxyapatite. Hydroxyapatite composite with polymers can be made into porous scaffolds, hydrogels, and coatings for bone repair. Hydroxyapatite/polymer composites can accelerate bone reconstruction with a slow release of loaded drugs and cytokines due to their bionic extracellular matrix structure and function. Based on the diversity of causes of bone defects and the fact that bone repair is a complex continuous process involving multiple biological factors and proteins, repair materials with mechanical properties matching bone tissue, degradation processes synchronized with bone repair, and efficient osteogenesis and vascularization need to be further investigated. [ABSTRACT FROM AUTHOR]

Severe loss of bone mass may require grafting, and, among the alternatives available, there are natural biomaterials that can act as scaffolds for the cell growth necessary for tissue regeneration. Collagen and elastin polymers are a good alternative due to their biomimetic properties of bone tissue, and their characteristics can be improved with the addition of polysaccharides such as chitosan and bioactive compounds such as jatoba resin and pomegranate extract due to their antigenic actions. The aim of this experimental protocol was to evaluate bone neoformation in experimentally made defects in the mandible of rats using polymeric scaffolds with plant extracts added. Thirty rats were divided into group 1, with a mandibular defect filled with a clot from the lesion and no graft implant (G1-C, n = 10); group 2, filled with collagen/chitosan/jatoba resin scaffolds (G2-CCJ, n = 10); and group 3, with collagen/nanohydroxyapatite/elastin/pomegranate extract scaffolds (G3-CHER, n = 10). Six weeks after surgery, the animals were euthanized and samples from the surgical areas were submitted to macroscopic, radiological, histological, and morphometric analysis of the mandibular lesion repair process. The results showed no inflammatory infiltrates in the surgical area, indicating good acceptance of the scaffolds in the microenvironment of the host area. In the control group (G1), there was a predominance of reactive connective tissue, while in the grafted groups (G2 and G3), there was bone formation from the margins of the lesion, but it was still insufficient for total bone repair of the defect within the experimental period standardized in this study. The histomorphometric analysis showed that the mean percentage of bone volume formed in the surgical area of groups G1, G2, and G3 was 17.17 ± 2.68, 27.45 ± 1.65, and 34.07 ± 0.64 (mean ± standard deviation), respectively. It can be concluded that these scaffolds with plant extracts added can be a viable alternative for bone repair, as they are easily manipulated, have a low production cost, and stimulate the formation of new bone by osteoconduction. [ABSTRACT FROM AUTHOR]

The development of hydroxyapatite (HAp) and polyether ether ketone (PEEK) biocomposites has been extensively studied for bone repair applications due to the synergistic properties of the involved materials. In this study, we aimed to develop HAp/PEEK biocomposites using high-energy ball milling, with HAp concentrations (20%, 40%, and 60% w/v) in PEEK, to evaluate their physicochemical, mechanical, cytotoxicity, and antimicrobial properties for potential applications in Tissue Engineering (TE). The biocomposites were characterized by structure, morphology, apparent porosity, diametral compression strength, cytotoxicity, and antimicrobial activity. The study results demonstrated that the HAp/PEEK biocomposites were successfully synthesized. The C2 biocomposite, containing 40% HAp, stood out due to the optimal distribution of HAp particles in the PEEK matrix, resulting in higher compression strength (246 MPa) and a homogeneous microstructure. It exhibited antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, with no cytotoxicity observed. These properties make the C2 biocomposite promising for regenerative medicine applications, combining mechanical strength, bioactivity, and biocompatibility.

Polymer is one material that can be used as a fixation to repair fractured or broken bones. However, polymers are soft and ductile, so modifying them by adding hydroxyapatite as a filler is necessary. Polyethylene is a high-density polymer with more potent material properties to be utilized as a matrix. The PE-HAp composites were synthesized by compacting and heating the composition percentage of Hap 25%, 35% and 45%. Based on the characterization results using XRD, FTIR, and hardness test instruments, it is concluded that the addition of HAp composition results in better composite mechanical properties. The material properties are improving, increasing the hardness value (shore A) by 63 shore A. The hardness value increases because the composite properties are more compact, and the PE matrix physically binds the HAp filler. This is reinforced by XRD and FTIR characterization results, with no new compounds formed and no new molecular vibrational patterns in the FTIR spectrum. [ABSTRACT FROM AUTHOR]

Background: Hydroxyapatite (HA)-based ceramics are widely used as artificial bone substitutes due to their advantageous biological properties, which include biocompatibility, biological affinity, bioactivity, ability to drive bone formation, integration into bone tissue and induction of bone regeneration (in certain conditions). Phototherapy in bone regeneration is a therapeutic approach that involves the use of light to stimulate and accelerate the process of repair and regeneration of bone tissue. There are two common forms of phototherapy used for this purpose: Low-Level Laser Therapy (LLLT) and LED (Light Emitting Diode) Therapy. Understanding the mechanisms of laser therapy and its effects combined with hydroxyapatite has gaps. Therefore, this review was designed based on the PICO strategy (P: problem; I: intervention; C: control; O: result) to analyze the relationship between PBM therapy and hydroxyapatite. Methods: The bibliographic search, with the descriptors “hydroxyapatite AND low-level laser therapy” and “hydroxyapatite AND photobiomodulation” resulted in 43 articles in the PubMed/MEDLINE database, of which 1 was excluded for being a duplicate and another 33 due to inclusion/exclusion criteria, totaling 9 articles for qualitative analysis. In the Web of Science database, we obtained 40 articles, of which 7 were excluded for being duplicates, 1 for not having the full text available and another 17 due to inclusion/exclusion criteria, totaling 15 articles for qualitative analysis. Results: The most used biomaterial was composed of hydroxyapatite and β-tricalcium phosphate in a proportion of 70%–30%. In photobiomodulation, the gallium-aluminum-arsenide (GaAlAs) laser prevailed, with a wavelength of 780 nm, followed by 808 nm. Conclusions: The results indicated that the use of laser phototherapy improved the repair of bone defects grafted with the biomaterial, increasing the deposition of HA phosphate as indicated by biochemical estimators, spectroscopy and histological analyses.

The demand for novel tissue grafting and regenerative wound care biomaterials is growing as traditional options often fall short in biocompatibility, functional integration with human tissue, associated cost(s), and sustainability. Salmon aquaculture generates significant volumes of waste, offering a sustainable opportunity for biomaterial production, particularly in osteo-conduction/-induction, and de novo clinical/surgical bone regeneration. Henceforth, this study explores re-purposing salmon waste through a standardized pre-treatment process that minimizes the biological waste content, followed by a treatment stage to remove proteins, lipids, and other compounds, resulting in a mineral-rich substrate. Herein, we examined various methods—alkaline hydrolysis, calcination, and NaOH hydrolysis—to better identify and determine the most efficient and effective process for producing bio-functional nano-sized hydroxyapatite. Through comprehensive chemical, physical, and biological assessments, including Raman spectroscopy and X-ray diffraction, we also optimized the extraction process. Our modified and innovative alkaline hydrolysis–calcination method yielded salmon-derived hydroxyapatite with a highly crystalline structure, an optimal Ca/P ratio, and excellent biocompatibility. The attractive nano-scale cellular/tissular properties and favorable molecular characteristics, particularly well-suited for bone repair, are comparable to or even surpass those of synthetic, human, bovine, and porcine hydroxyapatite, positioning it as a promising candidate for use in tissue engineering, wound healing, and regenerative medicine indications.

Most electrospun scaffolds for bone tissue engineering typically use hydroxyapatite (HA) or beta tricalcium phosphate (β-TCP). However, the biological activity of these crystalline compounds can be limited due to their low solubility. Therefore, amorphous calcium phosphate (ACP) may be an alternative in bone repair scaffolds. This study analyzes the morphology, porosity, mechanical strength, and surface chemistry of electrospun scaffolds composed of polylactic acid and collagen integrated with hydroxyapatite (MHAP) or amorphous calcium phosphate (MACP). In addition, the in vitro biocompatibility, osteogenic differentiation, and growth factor production associated with bone repair using human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) are evaluated. The results show that the electrospun MHAP and MACP scaffolds exhibit a fibrous morphology with interconnected pores. Both scaffolds exhibit favorable biocompatibility and stimulate the proliferation and osteogenesis of hWJ-MSCs. However, cell adhesion and osteocalcin production are greater in the MACP scaffold compared to the MHAP scaffold. In addition, the MACP scaffold shows significant production of bone-repair-related growth factors such as transforming growth factor-beta 1 (TGF-β1), providing a solid basis for its use in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Bone lesions have the capacity for regeneration under normal conditions of the bone metabolism process. However, due to the increasing incidence of major traumas and diseases that cause bone-mineral deficiency, such as osteoporosis, scaffolds are needed that can assist in the bone regeneration process. Currently, natural polymeric scaffolds and bioactive nanoparticles stand out. Therefore, the objective of the study was to evaluate the osteoregenerative potential in tibiae of healthy and ovariectomized rats using mineralized collagen and nanohydroxyapatite (nHA) scaffolds associated with elastin. The in-vivo experimental study was performed with 60 20-week-old Wistar rats, distributed into non-ovariectomized (NO) and ovariectomized (O) groups, as follows: Controls (G1-NO-C and G4-O-C); Collagen with nHA scaffold (G2-NO-MSH and G5-O-MSH); and Collagen with nHA and elastin scaffold (G3-NO-MSHC and G6-O-MSHC). The animals were euthanized 6 weeks after surgery and the samples were analyzed by macroscopy, radiology, and histomorphometry. ANOVA and Tukey tests were performed with a 95% CI and a significance index of p < 0.05. In the histological analyses, it was possible to observe new bone formed with an organized and compact morphology that was rich in osteocytes and with maturity characteristics. This is compatible with osteoconductivity in both matrices (MSH and MSHC) in rats with normal conditions of bone metabolism and with gonadal deficiency. Furthermore, they demonstrated superior osteogenic potential when compared to control groups. There was no significant difference in the rate of new bone formation between the scaffolds. Ovariectomy did not exacerbate the immune response but negatively influenced the bone-defect repair process. [ABSTRACT FROM AUTHOR]

Background: Hydroxyapatite (HA)-based ceramics are widely used as artificial bone substitutes due to their advantageous biological properties, which include biocompatibility, biological affinity, bioactivity, ability to drive bone formation, integration into bone tis sue and induction of bone regeneration (in certain conditions). Phototherapy in bone regeneration is a therapeutic approach that involves the use of light to stimulate and accelerate the process of repair and regeneration of bone tissue. There are two common forms of phototherapy used for this purpose: Low-Level Laser Therapy (LLLT) and LED (Light Emitting Diode) Therapy. Understanding the mechanisms of laser therapy and its effects combined with hydroxyapatite has gaps. Therefore, this review was designed based on the PICO strategy (P: problem; I: intervention; C: control; O: result) to analyze the relationship between PBM therapy and hydroxyapatite. Methods: The bibliographic search, with the descriptors "hydroxyapatite AND low-level laser therapy" and "hydroxyapatite AND photobiomodulation" resulted in 43 articles in the PubMed/MEDLINE database, of which 1 was excluded for being a duplicate and another 33 due to inclusion/exclusion criteria, totaling 9 articles for qualitative analysis. In the Web of Science database, we obtained 40 articles, of which 7 were excluded for being duplicates, 1 for not having the full text available and another 17 due to inclusion/exclusion criteria, totaling 15 articles for qualitative analysis. Results: The most used biomaterial was composed of hydroxyapatite and ß-tricalcium phosphate in a proportion of 70%-30%. In photobiomodulation, the gallium-aluminum-arsenide (GaAlAs) laser prevailed, with a wavelength of 780 nm, followed by 808 nm. Conclusions: The results indicated that the use of laser phototherapy improved the repair of bone defects grafted with the biomaterial, increasing the deposition of HA phosphate as indicated by biochemical estimators, spectroscopy and histological analyses. [ABSTRACT FROM AUTHOR]

Severe loss of bone mass may require grafting, and, among the alternatives available, there are natural biomaterials that can act as scaffolds for the cell growth necessary for tissue regeneration. Collagen and elastin polymers are a good alternative due to their biomimetic properties of bone tissue, and their characteristics can be improved with the addition of polysaccharides such as chitosan and bioactive compounds such as jatoba resin and pomegranate extract due to their antigenic actions. The aim of this experimental protocol was to evaluate bone neoformation in experimentally made defects in the mandible of rats using polymeric scaffolds with plant extracts added. Thirty rats were divided into group 1, with a mandibular defect filled with a clot from the lesion and no graft implant (G1-C, n = 10); group 2, filled with collagen/chitosan/jatoba resin scaffolds (G2-CCJ, n = 10); and group 3, with collagen/nanohydroxyapatite/elastin/pomegranate extract scaffolds (G3-CHER, n = 10). Six weeks after surgery, the animals were euthanized and samples from the surgical areas were submitted to macroscopic, radiological, histological, and morphometric analysis of the mandibular lesion repair process. The results showed no inflammatory infiltrates in the surgical area, indicating good acceptance of the scaffolds in the microenvironment of the host area. In the control group (G1), there was a predominance of reactive connective tissue, while in the grafted groups (G2 and G3), there was bone formation from the margins of the lesion, but it was still insufficient for total bone repair of the defect within the experimental period standardized in this study. The histomorphometric analysis showed that the mean percentage of bone volume formed in the surgical area of groups G1, G2, and G3 was 17.17 ± 2.68, 27.45 ± 1.65, and 34.07 ± 0.64 (mean ± standard deviation), respectively. It can be concluded that these scaffolds with plant extracts added can be a viable alternative for bone repair, as they are easily manipulated, have a low production cost, and stimulate the formation of new bone by osteoconduction.

BACKGROUND: Autologous and allogeneic bone currently used for bone repair has limited sources, complications in the donor area, potential risk of disease transmission, immune rejection, and high prices, which have limited clinical applications. Artificial bone repair materials have been widely studied as bone graft replacement materials. OBJECTIVE: To summarize the current status of research on metal ion-doped modified hydroxyapatite for bone tissue repair. METHODS: The articles collected in PubMed, Web of Science, CNKI and Wanfang databases were searched from January 2000 to May 2022. The Chinese and English search terms were “metal ion, hydroxyapatite, doping modification, bone repair”. Finally, 61 articles were included for review. RESULTS AND CONCLUSION: (1) Ion doped hydroxyapatite has good characteristics. Strontium can enhance the osteogenesis of osteoblasts and inhibit osteoclast mediated bone resorption. Strontium doped hydroxyapatite has unique advantages in the repair of osteoporotic bone defects. (2) Copper, zinc, silver, magnesium and iron have certain antibacterial activity, among which silver and zinc have excellent antibacterial activity. Doping modified hydroxyapatite is of great significance for the prevention and treatment of orthopedic infections. (3) Copper can promote the migration of vascular endothelial cells and increase angiogenesis. Copper doped hydroxyapatite can be used to repair bone tissue lacking blood vessels. Barium has developing property, and it can be compounded with hydroxyapatite and other materials to prepare developing bone repair materials. (4) Strontium Iron Co doped hydroxyapatite can regulate cellular immunity and promote angiogenesis and bone formation. Magnesium, zinc strontium doped hydroxyapatite can induce a weak alkaline environment conducive to osteogenesis, and has excellent osteogenic ability. (5) A certain amount of magnesium doped hydroxyapatite has the compressive strength matching with cortical bone, and is expected to be used for bone tissue repair in weight-bearing sites. Low concentration ion doping can improve the mechanical properties and osteogenic activity of hydroxyapatite, and endow it with antibacterial activity, angiogenesis promotion, immune regulation, and so on. (6) When the ion concentration is too high, it will produce toxic effects. At present, there is no final conclusion about the optimal doping concentration of each ion, which needs to be further studied in the future. (7) The mechanism of ion involvement in bone metabolism and whether it will affect other cell activities need to be explored. How to realize the slow degradation of implant materials and the slow release of metal ions to match the process of bone repair needs to be further studied. (8) Optimizing the synthesis method and ion doping technology of hydroxyapatite to prepare materials that match the mechanical properties of natural bone is a research direction in the future. [ABSTRACT FROM AUTHOR]

Glasses and nanodiamonds have been widely used as biomaterials, particularly in orthopedics. Biomolecule-derived materials are also gaining popularity in biomedical applications. Therefore, a biomolecule-derived glass with in situ formed nanodiamonds could be interesting material. The biomolecule-derived glass obtained in this study was synthesized by melt-quenching adenosine triphosphate-disodium. According to spectroscopic studies such as Raman spectroscopy, FTIR, and XPS, the glass formed from the phosphate groups of ATP is predominantly made of metaphosphate. The TEM, XPS, and Raman spectroscopic analysis confirm the in situ conversion of the organic portion of the ATP molecule into nanodiamonds. The confocal microscopy also reveals the fluorescence property of the nanodiamonds. In vitro experiments further demonstrate that the glass is non-cytotoxic, bioactive, and angiogenic, implying that it could be used in bone repair. This study also establishes that phosphate glass supports nanodiamonds formation and that biomolecule can form glass and nanodiamonds under the right conditions. [ABSTRACT FROM AUTHOR]

Porosity is a key feature in dictating the overall performance of biomedical scaffolds, with special relevance to mechanical properties. Usually, compressive strength and elastic modulus are the main parameters used to determine the potential mechanical suitability of porous scaffolds for bone repair. However, their assessment may not be so easy from an experimental viewpoint and, especially if the porosity is high, so reliable for brittle bioceramic foams. Hence, assessing the relationship between porosity and mechanical properties based only on the constitutive parameters of the solid material is a challenging and important task to predict the scaffold performance for optimization during design. In this work, a set of equations was used to predict the compressive strength and elastic modulus of bone-like hydroxyapatite scaffolds produced by digital light processing-based vat photopolymerization (total porosity about 80 vol.%). The compressive strength was found to depend on total porosity, following a power-law approximation. The relationship between porosity and elastic modulus was well fitted by second-order power law, with relative density and computational models obtained by numerical simulations.

Craniofacial tissue-engineered techniques have significantly improved over the past 20 years as a result of developments in engineering and in material science. The regeneration of the craniofacial tissue is frequently complicated due to the craniofacial region's complexity, which includes bone, cartilage, soft tissue, and neurovascular bundles. It is now possible to construct tissues in the lab using scaffolds, cells, and physiologically active chemicals. For bone repair/augmentation, the biomaterials are classified into natural like "collagen, fibrin, alginate, silk, hyaluronate, chitosan" and synthetic like "polyethyleneglycol, poly-e-caprolactone, polyglycolic acid" and some bioceramics "tricalcium phosphate, hydroxyapatite, biphasic calcium phosphate, and the bioactive glasses" along with metals certain (Titanium and Zirconia ) and as this is part of advanced tissue engineering in dentistry there are some bioactive restorative materials like mineral trioxide aggregate and biodentine. The newer advanced techniques like 3D printed templates present a framework for achieving the three pillars of tissue engineering: healing, rebuilding and rejuvenation. The field of tissue engineering has recently become interested in 3D printing, also known as "Additive Manufacturing", which is a ground-breaking technique that allows for the printing of patient-specific scaffolds, medical devices, multiscale, biomimetic/intricate cytoarchitecture/function-structure hierarchies and multicellular tissues in complex microenvironments. Biopolymers use is dependent on meeting the criteria for various scaffolds, including mechanical integrity, thermal stability, chemical composition, along with biological properties. Researchers have developed a revolutionary 4D bioprinting technique using cell traction forces and they are used to develop intricate dynamic structures, smart medical devices, or complex human organs. [ABSTRACT FROM AUTHOR]

Abstract Hydroxyapatite (HA) bioceramics have been extensively employed as bone tissue scaffolds owing to their biodegradability and osteoinductivity. In our work, HA, a significant component of natural bone tissue used as the raw material to produce porous scaffolds employing three‐dimensional (3D)‐printing technology. Physical and chemical properties, porosity, and compression resistance of the scaffolds were investigated in vitro. The scaffold was confirmed to have a large number of interconnected pore structures on the surface and inside HA scaffolds showed good cell compatibility and cell adhesion in cell text. To analyze the effect of the scaffold on bone repair and regeneration in vivo, the large‐size defect of beagle skull was repaired with a 3D printing group and an autologous bone group (ABG) for 8 months. Images and histological analysis of the 3D printing group indicated better integration with adjacent tissues. However, there were obvious gaps in the ABG, which indicates weak bone regeneration ability of this group due to unmatched implant dimension. Immunohistochemistry and immunofluorescence results showed that 3D‐printed scaffolds had a highly vascularized structure. This study indicates that 3D‐printed bioceramics scaffolds that are osteoinductivity and biodegradable have great potential in maxillofacial bone regeneration.

Calcium phosphate cement (CPC) is a material used to fill bone defects. Its advantages include being able to fill irregularly shaped spaces, its similarity to bone tissue, and ease of bio- degradation. However, insufficient durability and unpredictable rate of resorption limit CPC use. Objective. Study the dynamics of morphological changes in rat femurs after implanting two types of CPC based on metastable α'-tricalcium phosphate (α'--TCP) into defects in the distal metaphysis. Methods. 42 male white rats were used in the study. In each rat, defects were created in the distal metaphysis of the left femur and filled with one of the two types of CPC. The animals were split into two groups: І (n = 21) -- CPC based on α'--TCP powder; ІІ (n = 21) -- CPC based on α'--TCP powder reinforced with hydroxyapatite (HA) whiskers (4 % mass). Both varieties of CPC were developed and prepared at the Department of Solid-State Physics at the V. N. Karazin Kharkiv National University (Ukraine). 14, 30, and 60 days after the surgery, the animals were sacrificed, and histological analyses were performed. Results. For both types of CPC, inflammation was not observed in the region around the implant at 14, 30, or at 60 days. Bone tissue formed on the surface of the materials. The stages of bone repair were similar to the known stages of bone repair. As a result of the resorption of the CPC, 60 days after surgery the CPC comprised 26.83 % of the area of the defect in group I and 29.93 % in group II. The rest of the area was composed of lamellar bone. The two groups did not differ significantly in rate of CPC re- sorption or bone tissue formation. Conclusions. The two types of CPC studied, based on α'--TCP (group I) and α'--TCP reinforced with HA whiskers (group II), are biocompatible, osteoconductive, and osteoinductive. In addition, these materials are biodegradable and, with time, are replaced by bone tissue. [ABSTRACT FROM AUTHOR]

Strategies for the production of new nanocomposites that promote bone tissue regeneration are important, particularly those that enhance the osteoinduction of hydroxyapatite in situ. Here, we studied and report the synthesis of nanohydroxyapatite and titanate nanotube (nHAp/TiNT) composites formulated at different concentrations (1, 2, 3, and 10 wt % TiNT) by means of a wet aqueous chemical reaction. The addition of TiNT affects the morphology of the nanocomposites, decreasing the average crystallite size from 54 nm (nHAp) to 34 nm (nHAp/TiNT10%), while confirming its interaction with the nanocomposite. The crystallinity index (CI) calculated by Raman spectroscopy and XRD showed that the values decreased according to the increase in TiNT concentration, which confirmed their addition to the structure of the nanocomposite. SEM images showed the presence of TiNTs in the nanocomposite. We further verified the potential cytotoxicity of murine fibroblast cell line L929, revealing that there was no remarkable cell death at any of the concentrations tested. In vivo regenerative activity was performed using oophorectomized animal (rat) models organized into seven groups containing five animals each over two experimental periods (15 and 30 days), with bone regeneration occurring in all groups tested within 30 days; however, the nHAp/TiNT10% group showed statistically greater tissue repair, compared to the untreated control group. Thus, the results of this study demonstrate that the presently formulated nHAp/TiNT nanocomposites are promising for numerous improved bone tissue regeneration applications. [ABSTRACT FROM AUTHOR]

Polymer-based scaffolds with different degradability have been investigated to screen the matrix whose degradation rate is more closely matched with the bone regeneration rate. However, these comparisons are inclined to be compromised by the animal individual differences. In this study, we constructed an integrated scaffold model comprising four parts with different degradability and bioactivity to achieve an in situ comparison of bone regeneration ability of different scaffolds. Slow-degradable polycaprolactone (PCL), fast-degradable poly (lactic-co-glycolic acid) (PLGA), and silica-coated PCL and PLGA scaffolds were assembled into a round sheet to form a hydroxyapatite (HA)-free integrated scaffold. HA-doped PCL, PLGA, and silica-coated PCL and PLGA scaffolds were assembled to create an HA-incorporated integrated scaffold. The in vivo experimental results demonstrated that the local acid microenvironment caused by the rapid degradation of PLGA interfered with the osteogenic process promoted by PCL-based scaffolds in defect areas implanted with HA-free integrated scaffolds. Since the incorporation of HA alleviated the acidic microenvironment to some extent, each scaffold in HA-incorporated scaffolds exhibited its expected bone regeneration capacity. Consequently, it is feasible to construct an integrated structure for comparing the osteogenic effects of various scaffolds in situ, when there is no mutual interference between the materials. The strategy presented in this study inspired the structure design of biomaterials to enable in situ comparison of bone regeneration capacity of scaffolds. [Display omitted] • Bone repair effects of different scaffolds were compared in the same animal model. • An integrated structure composed of multiple parts with varying characteristics. • HA reduced the interference of PLGA acid-byproduct on osteogenesis of other parts. [ABSTRACT FROM AUTHOR]

Bone lesions have the capacity for regeneration under normal conditions of the bone metabolism process. However, due to the increasing incidence of major traumas and diseases that cause bone-mineral deficiency, such as osteoporosis, scaffolds are needed that can assist in the bone regeneration process. Currently, natural polymeric scaffolds and bioactive nanoparticles stand out. Therefore, the objective of the study was to evaluate the osteoregenerative potential in tibiae of healthy and ovariectomized rats using mineralized collagen and nanohydroxyapatite (nHA) scaffolds associated with elastin. The in-vivo experimental study was performed with 60 20-week-old Wistar rats, distributed into non-ovariectomized (NO) and ovariectomized (O) groups, as follows: Controls (G1-NO-C and G4-O-C); Collagen with nHA scaffold (G2-NO-MSH and G5-O-MSH); and Collagen with nHA and elastin scaffold (G3-NO-MSHC and G6-O-MSHC). The animals were euthanized 6 weeks after surgery and the samples were analyzed by macroscopy, radiology, and histomorphometry. ANOVA and Tukey tests were performed with a 95% CI and a significance index of p < 0.05. In the histological analyses, it was possible to observe new bone formed with an organized and compact morphology that was rich in osteocytes and with maturity characteristics. This is compatible with osteoconductivity in both matrices (MSH and MSHC) in rats with normal conditions of bone metabolism and with gonadal deficiency. Furthermore, they demonstrated superior osteogenic potential when compared to control groups. There was no significant difference in the rate of new bone formation between the scaffolds. Ovariectomy did not exacerbate the immune response but negatively influenced the bone-defect repair process.

Most electrospun scaffolds for bone tissue engineering typically use hydroxyapatite (HA) or beta tricalcium phosphate (β-TCP). However, the biological activity of these crystalline compounds can be limited due to their low solubility. Therefore, amorphous calcium phosphate (ACP) may be an alternative in bone repair scaffolds. This study analyzes the morphology, porosity, mechanical strength, and surface chemistry of electrospun scaffolds composed of polylactic acid and collagen integrated with hydroxyapatite (MHAP) or amorphous calcium phosphate (MACP). In addition, the in vitro biocompatibility, osteogenic differentiation, and growth factor production associated with bone repair using human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) are evaluated. The results show that the electrospun MHAP and MACP scaffolds exhibit a fibrous morphology with interconnected pores. Both scaffolds exhibit favorable biocompatibility and stimulate the proliferation and osteogenesis of hWJ-MSCs. However, cell adhesion and osteocalcin production are greater in the MACP scaffold compared to the MHAP scaffold. In addition, the MACP scaffold shows significant production of bone-repair-related growth factors such as transforming growth factor-beta 1 (TGF-β1), providing a solid basis for its use in bone tissue engineering.

Objective：To discuss the technological process of platelet rich fibrin (PRF) /hydroxyapatite (HA) complex prepared by the“sandwich”method, and to evaluate its properties. Methods：The injectable PRF (I-PRF) and advanced PRF (A-PRF) were prepared with the centrifugation indexes of 700 r·min－1 × 3 min and 1 300 r·min－1 ×14 min, respectively, then they were combined with HA using the“sandwich” method. The microstructure of PRF/HA complex was observed under scanning electron microscope (SEM) after freeze drying；the material was immersed in the simulated body fluid (SBF), and the growth of a bone-like layer on the surface of HA was observed on the 2nd, 4th, 8th, and 16th days, respectively, and its mineralization ability was evaluated；the PRF/HA complex extract solution co-cultured with preosteoblast MC3T3-E1 cells of the mice and complete culture medium were used as experimental group and control group；after cultured for 1, 3 and 5 d, respectively, the proliferation activities of the preosteoblast MC3T3-E1 cells were evaluated by CCK-8 method. Two full-thickness cranial defect areas with a diameter of 6 mm were symmetrically established on both the sides of the sagittal suture in the Japanese white rabbits；one side implanted with PRF/HA complex was regarded as experimental group, the other side without any material implantion was regarded as control group；X-ray and cone beam CT (CBCT) were used on the surgical area to evaluate the bone formation performance of the rabbits in two groups 4 and 8 weeks after surgery. Results：The PRF/HA complex with a“sandwich”structure was successfully prepared, with the A-PRF on the outside and the I-PRF mixed with HA particles on the inside. The SEM observation results showed that the cross-section of the complex was an obvious threelayer structure, with the dense fibrin net on the outside and the porous HA particles attached by fibrin filaments on the inside. After being immersed in SBF, the mineralized nodules were formed on the surface of HA on the 2nd day, the bone-like layer was gradually established with the prolongation of the immersion time, and a lamellar structure was formed at the 16th day. The cell proliferation experiment results showed that compared with control group, the proliferation activities of the MC3T3-E1 cells in experimental group were significantly increased on the 1st, 3rd, and 5th days (P<0. 05) . The imaging observation results showed that the cranial defect in experimental group had obvious marginal osteogenesis 4 weeks after surgery and the new bone had almost completely filled the bone defect area 8 weeks after surgery, while the new bone formation of the cranial defect in control group was significantly decreased than that in experimental group. Conclusion：PRF/HA complex prepared by the“sandwich”method has a good mineralization ability and biocompatibility, and can promote the bone regeneration. [ABSTRACT FROM AUTHOR]

Porosity is a key feature in dictating the overall performance of biomedical scaffolds, with special relevance to mechanical properties. Usually, compressive strength and elastic modulus are the main parameters used to determine the potential mechanical suitability of porous scaffolds for bone repair. However, their assessment may not be so easy from an experimental viewpoint and, especially if the porosity is high, so reliable for brittle bioceramic foams. Hence, assessing the relationship between porosity and mechanical properties based only on the constitutive parameters of the solid material is a challenging and important task to predict the scaffold performance for optimization during design. In this work, a set of equations was used to predict the compressive strength and elastic modulus of bone-like hydroxyapatite scaffolds produced by digital light processing-based vat photopolymerization (total porosity about 80 vol.%). The compressive strength was found to depend on total porosity, following a power-law approximation. The relationship between porosity and elastic modulus was well fitted by second-order power law, with relative density and computational models obtained by numerical simulations. [ABSTRACT FROM AUTHOR]

There are several treatment methods available for bone repair, although the effectiveness becomes limited in cases of large defects. The objective of this pre-clinical protocol was to evaluate the grafting of hydroxyapatite/tricalcium phosphate (BCP) ceramic biomaterial (B; QualyBone BCP®, QualyLive, Amadora, Portugal) together with the heterologous fibrin biopolymer (FB; CEVAP/UNESP Botucatu, Brazil) and with photobiomodulation (PBM; Laserpulse®, Ibramed, Amparo, Brazil) in the repair process of bone defects. Fifty-six rats were randomly divided into four groups of seven animals each: the biomaterial group (G1/B), the biomaterial plus FB group (G2/BFB); the biomaterial plus PBM group (G3/B + PBM), and the biomaterial plus FB plus PBM group (G4/BFB + PBM). After anesthesia, a critical defect was performed in the center of the rats' parietal bones, then filled and treated according to their respective groups. The rats were euthanized at 14 and 42 postoperative days. Histomorphologically, at 42 days, the G4/BFB + PBM group showed a more advanced maturation transition, with more organized and mature bone areas forming concentric lamellae. A birefringence analysis of collagen fibers also showed a more advanced degree of maturation for the G4/BFB + PBM group. In the comparison between the groups, in the two experimental periods (14 and 42 days), in relation to the percentage of formation of new bone tissue, a significant difference was found between all groups (G1/B (5.42 ± 1.12; 21.49 ± 4.74), G2/BFB (5.00 ± 0.94; 21.77 ± 2.83), G3/B + PBM (12.65 ± 1.78; 29.29 ± 2.93), and G4/BFB + PBM (12.65 ± 2.32; 31.38 ± 2.89)). It was concluded that the use of PBM with low-level laser therapy (LLLT) positively interfered in the repair process of bone defects previously filled with the biocomplex formed by the heterologous fibrin biopolymer associated with the synthetic ceramic of hydroxyapatite and tricalcium phosphate. [ABSTRACT FROM AUTHOR]

Background: The invasive and complicated procedures involving the use of traditional stem cells limit their application in bone tissue engineering. Cell-free, tissue-engineered bones often have complex scaffold structures and are usually engineered using several growth factors (GFs), thus leading to costly and difficult preparations. Urine-derived stem cells (USCs), a type of autologous stem cell isolated noninvasively and with minimum cost, are expected to solve the typical problems of using traditional stem cells to engineer bones. In this study, a graphene oxide (GO)-modified silk fibroin (SF)/nanohydroxyapatite (nHA) scaffold loaded with USCs was developed for immunomodulation and bone regeneration. Methods: The SF/nHA scaffolds were prepared via lyophilization and cross-linked with GO using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS). Scaffolds containing various concentrations of GO were characterized using scanning electron microscopy (SEM), the elastic modulus test, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectrometer (XPS). Examinations of cell adhesion, proliferation, viability, morphology, alkaline phosphatase activity, and osteogenesis-related gene expression were performed to compare the osteogenesis-related biological behaviors of USCs cultured on the scaffolds. The effect of USC-laden scaffolds on the differentiation of macrophages was tested using ELISA, qRT-PCR, and immunofluorescence staining. Subcutaneous implantations in rats were performed to evaluate the inflammatory response of the USC-laden scaffolds after implantation. The scaffolds loaded with USCs were implanted into a cranial defect model in rats to repair bone defects. Micro-computed tomography (μCT) analyses and histological evaluation were performed to evaluate the bone repair effects. Results: GO modification enhanced the mechanical properties of the scaffolds. Scaffolds containing less than 0.5% GO had good biocompatibility and promoted USC proliferation and osteogenesis. The scaffolds loaded with USCs induced the M2-type differentiation and inhibited the M1-type differentiation of macrophages. The USC-laden scaffolds containing 0.1% GO exhibited the best capacity for promoting the M2-type differentiation of macrophages and accelerating bone regeneration and almost bridged the site of the rat cranial defects at 12 weeks after surgery. Conclusions: This composite system has the capacity for immunomodulation and the promotion of bone regeneration and shows promising potential for clinical applications of USC-based, tissue-engineered bones. [ABSTRACT FROM AUTHOR]

Strategies for the production of new nanocomposites that promote bone tissue regeneration are important, particularly those that enhance the osteoinduction of hydroxyapatite in situ. Here, we studied and report the synthesis of nanohydroxyapatite and titanate nanotube (nHAp/TiNT) composites formulated at different concentrations (1, 2, 3, and 10 wt % TiNT) by means of a wet aqueous chemical reaction. The addition of TiNT affects the morphology of the nanocomposites, decreasing the average crystallite size from 54 nm (nHAp) to 34 nm (nHAp/TiNT10%), while confirming its interaction with the nanocomposite. The crystallinity index (CI) calculated by Raman spectroscopy and XRD showed that the values decreased according to the increase in TiNT concentration, which confirmed their addition to the structure of the nanocomposite. SEM images showed the presence of TiNTs in the nanocomposite. We further verified the potential cytotoxicity of murine fibroblast cell line L929, revealing that there was no remarkable cell death at any of the concentrations tested. In vivo regenerative activity was performed using oophorectomized animal (rat) models organized into seven groups containing five animals each over two experimental periods (15 and 30 days), with bone regeneration occurring in all groups tested within 30 days; however, the nHAp/TiNT10% group showed statistically greater tissue repair, compared to the untreated control group. Thus, the results of this study demonstrate that the presently formulated nHAp/TiNT nanocomposites are promising for numerous improved bone tissue regeneration applications.

At the present time there are no consistently satisfactory treatment options for some challenging bone loss scenarios. We have previously reported on the properties of a novel 3D‐printed hydroxyapatite‐composite material in a pilot study, which demonstrated osteoconductive properties but was not tested in a rigorous, clinically relevant model. We therefore utilized a rat critical‐sized femoral defect model with a scaffold designed to match the dimensions of the bone defect. The scaffolds were implanted in the bone defect after being loaded with cultured rat bone marrow cells (rBMC) transduced with a lentiviral vector carrying the cDNA for BMP‐2. This experimental group was compared against 3 negative and positive control groups. The experimental group and positive control group loaded with rhBMP‐2 demonstrated statistically equivalent radiographic and histologic healing of the defect site (p > 0.9), and significantly superior to all three negative control groups (p < 0.01). However, the healed defects remained biomechanically inferior to the unoperated, contralateral femurs (p < 0.01). When combined with osteoinductive signals, the scaffolds facilitate new bone formation in the defect. However, the scaffold alone was not sufficient to promote adequate healing, suggesting that it is not substantially osteoinductive as currently structured. The combination of gene therapy with 3D‐printed scaffolds is quite promising, but additional work is required to optimize scaffold geometry, cell dosage and delivery. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bone tissue engineering scaffolds are considered as a potential alternative to traditional bone grafting due to their unlimited supply and lack of disease transmission. However, bone tissue engineering scaffolds have not entered clinical practice due to some limitations or challenges. OBJECTIVE: To discuss the clinical and mechanical requirements of bone scaffolds, summarize the biomaterials used in various scaffolds and the challenges and future trends in the field of bone tissue engineering scaffolds. METHODS: Search words were “bone tissue engineering, bone scaffolding, biomaterials, bone histology, bone defect, bone repair” in English and Chinese. Relevant literature on bone tissue engineering scaffolds published from 2005 to 2020 was searched by computer in CNKI, Wanfang database, and PubMed database. Systematic summary, summary and analysis were conducted to comprehensively describe the new progress and challenges in the research on bone tissue engineering scaffolds. RESULTS AND CONCLUSION: At present, natural derived biomaterials, synthetic biomaterials and metal materials are mainly used in the preparation of bone tissue engineering scaffolds. These materials have been used in the manufacture of bionic scaffolds to support the growth and regeneration of bone tissue. Although great progress has been made in the research of scaffold materials for bone tissue engineering, there are still many key obstacles to be cleared for the real application of bone tissue engineering in clinical practice. The future research focus is to find some materials similar to human autogenous bone tissue structure and performance, and carry out bionic design on them, so as to develop tissue engineered artificial bone similar to human autogenous bone structure and performance. [ABSTRACT FROM AUTHOR]

Poly(methyl methacrylate) (PMMA)‐based bone cements (BCs) can be defined as a family of materials that consist of powder and liquid phases which after mixing form a plastic paste that can self‐set once implanted in the human body. PMMA‐based BCs are easily molded and adapted to complex bone cavities or used in orthodontic applications to restore dental damage. The main advantages of the use of cement are the excellent primary fixation between bone and implant and, therefore, the faster recovery of the patient. Despite the initial success rate of implant fixation with BCs, they have some disadvantages such as local tissue damage due to exothermic polymerization reactions, mechanical mismatch between native bone and cement, lack of bone regeneration and bioactivity and poor mechanical properties which may cause the failure of the BCs. BCs are still considered as a top option for bone repair. Due to the disadvantages highlighted, research has focused on alternative materials used with PMMA‐based BCs. This review aims to critically review the BCs and emerging materials used in combination with PMMA‐based BCs. These materials include titania, apatite–wollastonite (A‐W), glass ceramic (GC) and hydroxyapatite (HA). The review discusses the properties of these materials and their pathway to clinical study. Among the various kinds of reinforcement, HA has been extensively used. So, in this review, we compare the effects of HA as reinforcement in PMMA‐based BCs. Upcoming study of PMMA‐based BCs should concentrate on trialing combinations of these reinforcing agents as this might improve beneficial characteristics. © 2020 Society of Industrial Chemistry [ABSTRACT FROM AUTHOR]

BACKGROUND: Bioglass has high brittleness and poor mechanical strength, which limits its application in bone defect of bearing part. Nitrogen oxide glass has higher strength and hardness. Therefore, nitriding treatment is expected to improve the mechanical strength of bioglass. OBJECTIVE: To analyze the effects of nitridation on the porosity, compressive strength, bending strength, degradation performance and mineralization activity of porous bioglass scaffolds. METHODS: This experiment was based on silicate glass (SiO2-CaO-P2O5-Na2O-ZnO), and nitriding it (SiO2 was replaced by 0%, 2%, 4%, 6% Si3N4, respectively). The basic glass (SiO2-CaO-P2O5-Na2O-ZnO-Si3N4) was prepared by melting method. The polyurethane foam was used as template and organic foam impregnation method was used to prepare porous bioglass scaffolds. The porosity, compressive strength, bending strength, and degradation performance in vitro of the porous bioglass scaffolds were measured in four groups. Four groups of scaffolds were immersed in simulated body fluid for 7 days. The surface morphology of the scaffold was observed with the scanning electron microscope. RESULTS AND CONCLUSION: (1) The porosity of the four groups had no statistical difference (P > 0.05). (2) With increased Si3N4 content, compressive strength and bending strength of porus bioglass scaffold increased, and there was statistical difference between each group (P < 0.05). (3) With increased Si3N4 content, the degradation performance of porous bioglass scaffolds decreased gradually in vitro. (4) Scanning electron microscope revealed that typical hydroxyapatite membrane was formed on the surface of porous bioglass scaffold without nitriding treatment and porous bioglass scaffold containing 2% Si3N4, but no hydroxyapatite membrane was formed in the other two groups. (5) Nitriding treatment can significantly enhance the mechanical strength of bioglass, but can reduce its degradation performance and mineralization activity in vitro. [ABSTRACT FROM AUTHOR]

A suitable microenvironment provided by artificial granule scaffold plays a critical regulatory role in bone repairing progression. Till now, it is still a challenge to prepare large hydroxyapatite granules (millimetre level) which provide beneficial physical and chemical stimulation for bone reconstruction. Herein, we developed a facile synthetic strategy for synthesizing hydroxyapatite granules by a repaid gelling method. Also, the satisfying drug-releasing behavior of these granules further proves their potential prospect for bone tissue engineering as bone filler. [ABSTRACT FROM AUTHOR]

Preventive and regenerative techniques have been suggested to minimize the aesthetic and functional effects caused by intraoral bone defects, enabling the installation of dental implants. Among them, porous three-dimensional structures (scaffolds) composed mainly of bioabsorbable ceramics, such as hydroxyapatite (HAp) and β-tricalcium phosphate (β-TCP) stand out for reducing the use of autogenous, homogeneous, and xenogenous bone grafts and their unwanted effects. In order to stimulate bone formation, biodegradable polymers such as cellulose, collagen, glycosaminoglycans, polylactic acid (PLA), polyvinyl alcohol (PVA), poly-ε-caprolactone (PCL), polyglycolic acid (PGA), polyhydroxylbutyrate (PHB), polypropylenofumarate (PPF), polylactic-co-glycolic acid (PLGA), and poly L-co-D, L lactic acid (PLDLA) have also been studied. More recently, hybrid scaffolds can combine the tunable macro/microporosity and osteoinductive properties of ceramic materials with the chemical/physical properties of biodegradable polymers. Various methods are suggested for the manufacture of scaffolds with adequate porosity, such as conventional and additive manufacturing techniques and, more recently, 3D and 4D printing. The purpose of this manuscript is to review features concerning biomaterials, scaffolds macro and microstructure, fabrication techniques, as well as the potential interaction of the scaffolds with the human body. [ABSTRACT FROM AUTHOR]

Current study was planned to evaluate effects of eggshell-derived hydroxyapatite (eHA) on healing of radius bone gap in rabbits. Hydroxyapatite was prepared previously from avian eggshell using hydrothermal method and applied to fill an experimentally induced (1 cm) gap at the mid shaft of the radius bone reaching marrow cavity in fifteen male rabbits using left forelimbs as a treated group, while in the right forelimbs the induced bone gaps left without additives and considered as a control group. The clinical, macroscopical, radiological and histopathological parameters indicated a significantly differences in bone growth and complete bridging the bone gaps between treated and control groups at intervals (4, 8 and 12) weeks post operation. In addition to well incorporation of eHA powder with the bone gap in treated groups. In conclusion avian eHA powder considered as a good biocompatible graft material to repair a critical bone gap in rabbit model. [ABSTRACT FROM AUTHOR]

Background: Bone grafts have been used to enhance bone fracture healing in orthopedic surgery. Bone grafts enhance bone healing either by mechanical support or acting as a scaffold for bone formation. Fresh autograft is the most effective biomaterial because it is histocompatible with less complication about transmissible disease. Hydroxyapatite is a well-established material for bone repair and very comparable to natural apatite providing a strong biomechanical interlock with host tissue. Royal jelly is the principal food for the honeybee queen. This biomaterial has been demonstrated to have several pharmacological activities, such as antiallergic, antitumor and anti-inflammatory effects. Objectives: This study was design to evaluate the effect of concurrent using of Royal jelly with hydroxyapatite on bone healing in rabbit model. Methods: 15 adult rabbits weighting approximately 2 kg had been used. They were divided into three groups randomly. In first group (N = 5) mid radius bone defect created and left empty. The second group (N = 5) filled with hydroxy apatite alone and the last group (N = 5) filled with royal jelly and hydroxy apatite combination. Radiological evaluation performed on days14th, 28th and 42nd after operation. Histopathological evaluation was done on 56th postoperative day. Results: Radiological evaluation showed significant superior bone healing in hydroxyapatite and hydroxyapatite-Royal jelly groups in comparison to control group. Control group was the inferior group between three groups. There were not any significant differences between three groups in histopathological group. Conclusion: In conclusion our study showed the best results with using the hydroxyl apatite and Royal-jelly group because they provide not only scaffold for bone healing but also do, they provide some osteoinduction materials for bone healing.

Alginate capsules with cuttlebone-derived fillers were developed for bone repair applications. Prepared capsules were designed to be suitable for the treatment of small-sized bone loss provocative diseases, such as endodontic and periodontal diseases. Cuttlebone microparticles, as a source of calcium carbonate, or cuttlebone-derived hydroxyapatite microparticles were used as mineral fillers for the preparation of alginate capsules. The capsules were additionally covered with chitosan layer for the hard structure formation and improvement of adhesive properties. Encapsulation efficiency of dexamethasone as a model allopathic drug was 19 %, 24 % and 12 % for capsules with cuttlebone microparticles, capsules with cuttlebone-derived hydroxyapatite and capsules without any mineral filler (control group), respectively. We observed that chitosan coating and lyophilisation contributed for the preservation of spherical structure of alginate capsules with mineral fillers. Swelling study of dried capsules in simulated physiological environment (in phosphate buffer saline, pH = 7.2 at 37 °C temperature) showed that average swelling index of alginate-based capsules without mineral fillers was much higher in comparison to capsules with cuttlebone fillers: 121 %, 17 % and 3 % for control group, capsules with cuttlebone microparticles and capsules with cuttlebone-derived hydroxyapatite, respectively.DOI: http://dx.doi.org/10.5755/j01.ms.24.3.18858

BACKGROUND: The dense microstructure of biological scaffolds and the limitation of cell growth microenvironment are the two major difficulties in the application of biological scaffolds in bone tissue repair. OBJECTIVE: To prepare fluffy hydroxyapatite/polylactic acid composite fiber scaffold, so that cells can easily enter into the scaffold and to realize three-dimensional culture of bone marrow mesenchymal stem cells. METHODS: Fluffy hydroxyapatite/polylactic acid composite scaffold was prepared by using modified electrospinning technology combined with biomineralization. The physical and chemical properties of the fiber scaffold were measured and observed. Human bone marrow mesenchymal stem cells were inoculated on the fluffy hydroxyapatite/polylactic acid composite scaffold and traditional hydroxyapatite/polylactic acid composite scaffold. Cell proliferation,adherence and morphological changes were detected. RESULTS AND CONCLUSION: (1) The thickness of hydroxyapatite coating in the fluffy hydroxyapatite/polylactic acid composite scaffold was about 8.3 μm, most of hydroxyapatite fibers were in discrete state with a diameter of 8-14 μm. The fibers were connected by pores, and the pore diameter was (65士35)μm. The surface area, porosity and water absorption of the scaffold were significantly higher than those of the traditional scaffold (P < 0.01). (2) After 12 hours of culture, the adherence of bone marrow mesenchymalstem cells on the two scaffolds was similar, 83% and 81% cells adhered on the traditional and fluffy scaffolds，respectively.(3) After 7 days of culture, the number of proliferated cells in the fluffy hydroxyapatite/polylactic acid composite scaffold was significantly more than that in the traditional hydroxyapatite/polylactic acid composite scaffold (P < 0.01). (4) After 7 days of culture, FDA staining and scanning electric microscopy showed that cell-cell independent shape appeared in the traditional scaffold. A large number of cells appeared in the fluffy scaffold and grew into cell clusters with high cell activity, which formed a cell-fiber construction. These results indicate that this new type hydroxyapalite/polylactic acid composite scaffold is beneficial for cell entry and proliferation. [ABSTRACT FROM AUTHOR]

Zinc is an important element for bone structure and metabolism. Its interaction with hydroxyapatite has been investigated for the improvement of bone repair. The objective of this study was to evaluate the in vitro and in vivo biological response to nanostructured calcium alginate‐hydroxyapatite (HA) and zinc‐containing HA (ZnHA). Cytocompatibility was evaluated by applying PrestoBlue reagent after exposing murine pre‐osteoblast cells to extracts of each biomaterial microspheres. After physical and chemical characterization, the biomaterial microspheres were implanted in a critical size calvaria defect (8 mm) in Wistar rats (n = 30) that were randomly divided into the HA and ZnHA groups. Tissue samples were evaluated through histological and histomorphometric analyses after 1, 3, and 6 months (n = 5). The results showed cellular viability for both groups compared to the negative control, and no differences in metabolic activity were observed. The HA group presented a significant reduction of biomaterial compared with the ZnHA group in all experimental periods; however, a considerable amount of new bone formation was observed surrounding the ZnHA spheres at the 6‐month time point compared with the HA group (p <.05). Both biomaterials were biocompatible, and the combination of zinc with hydroxyapatite was shown to improve bone repair. [ABSTRACT FROM AUTHOR]

Shortening the period of bone repair based on BaTiO3/hydroxyapatite(HA) composites with osteoconductivity and osteoinductivity is important. However, when the piezoelectric properties of composites are matched with natural bone, the content of non-degradable BaTiO3 needs to reach 90%, which may not conducive to clinical application. The barium titanate content in the composite was reduced by doping Er3+ into the BaTiO3 of BaTiO3/HA composites with enhanced piezoelectric properties. The piezoelectric constant and compressive strength of composites increased with the increase of Er3+-doped barium titanate (BTEr) content. Appropriate piezoelectric stimulation can promote the growth of osteoblasts. 70% BTEr/30% HA is more beneficial to the proliferation of osteoblasts than 70% BaTiO3/30% HA. [ABSTRACT FROM AUTHOR]

The intensive development of reconstructive surgery and traumatology provides a stable demand for new materials for implants. Of particular interest are materials based on hydroxyapatite, which are chemically close to the elemental composition and structure of bone and have similar bioactive properties. The aim of this work was to obtain porous composite materials based on hydroxyapatite and a copolymer of lactide and glycolide with properties suitable for use as a material for bone implants. The phase and elemental composition of composites was investigated by infrared spectroscopy, X-ray diffraction, and X-ray photoelectronic spectroscopy methods, and it was established how the production process affects the composition of materials. Regularities of the formation of porosity by the methods of low-temperature adsorption of nitrogen, immersion in a liquid (determination of the pore space volume), measurement of the diffusion coefficient through the material (Franz cell), and surface properties of composite materials by the Hammett indicator method, by the lying drop method were revealed. Regularities were established between the surface properties and the composition of materials and their biocompatibility determined using monocytes isolated from human peripheral blood.

The application of various materials in biomedical procedures has recently experienced rapid growth. One of the areas is the treatment of many of different types of bone-related diseases and disorders by using biodegradable polymer-ceramic composites. We have developed a material based on cryogel polyvinyl alcohol, mineralized with calcium phosphate. Composites were obtained by cyclic freezing-thawing, the synthesis of calcium phosphates was carried out in situ under the influence of microwave radiation with heating and stirring. The components of the composites were determined using the methods of IR-spectroscopy and scanning electron microscopy and electron probe microanalyzer, as well as their morphology and surface properties. The biological compatibility of the material was investigated in vivo for a Wistar rat. The assessment of the quality of bone formation between the cryogel-based implant and the damaged bone was carried out by computed tomography. An improvement in the consolidation of the bone defect is observed in the bone with the composite in comparison with the control bone.