The effect of a single injection of uniform-sized insulin-loaded PLGA microspheres on peri-implant bone formation

Titanium implants are widely used treatment modalities, with a long list of clinical successes in orthopaedics, orthopedics and maxillofacial surgery. However, early implant loss occurs in 4.4% of patients, and to overcome this issue, bioactive factors have been generally used for improving peri-implant bone formation. Recently, the role of insulin in the improvement of bone development and physiology has attracted considerable attention. Nevertheless, one injection of insulin could not have a persistent effect in the site for bone formation because of its fast metabolism and instability, leading to limited efficacy. Moreover, the wider size distribution of microspheres frequently leads to uncontrollable insulin release, which affects preparation repeatability, drug efficacy and reliability. Herein, we developed uniform-sized insulin-loaded poly(dl-lactic-co-glycolic acid) (PLGA) microspheres for injection around the metal implant. The results demonstrated that the microspheres had narrow size distribution (Span < 0.7) and bioactive insulin was sustainedly released from the microspheres over 45 days. These insulin-loaded PLGA microspheres exhibit good bioactivity to facilitate the proliferation of human bone marrow mesenchymal stromal cells (BMSCs). Expressions of ALP, OCN and mineralized matrix formations in the insulin-loaded PLGA group were significantly higher than those in other groups. Furthermore, in rabbit mandible models, a single injection of insulin-loaded PLGA microspheres around the titanium implant showed higher peri-implant bone formation and better osseointegration, as observed by histological analysis, micro-CT and biomechanics.

Titanium implants are widely used treatment modalities, with a long list of clinical successes in orthopaedics, orthopedics and maxillofacial surgery.     

Impact of exogenous metal ions on peri-implant bone metabolism: a review

The development of effective methods to promote the osseointegration of dental implants by surface modification is an area of intense research in dental materials science. Exogenous metal ions present in the implant and surface modifications are closely related to the bone metabolism around the implant. In the complex oral microenvironment, the release of metal ions caused by continuous corrosion of dental implants has an unfavorable impact on the surrounding tissue, and then affects osseointegration, leading to bad results such as loosening and falling off in the late stage of the implant. Besides, these ions can even be distributed in distant tissues and organs. Currently, surface modification techniques are being developed that involve different processing technologies including the introduction of exogenous metal ions with different properties onto the surface of implants to improve performance. However, most metal elements have some level of biological toxicity and can only be used within a safe concentration range to exert the optimum biological effects on recipients. In this paper, we review the adverse effects of metal ions on osseointegration and highlight the emerging applications for metal elements in improving the performance of dental implants.

The development of effective methods to promote the osseointegration of dental implants by surface modification is an area of intense research in dental materials science.     

Defect-related luminescent nanostructured hydroxyapatite promotes mineralization through both intracellular and extracellular pathways

Hydroxyapatite (HAP) is a widely used biomaterial for bone tissue substitution due to its chemical similarity with the natural bone. Defect-related luminescent HAP materials have the same chemical composition as normal HAP and excellent biocompatibility. However, only few works have focused on the defect-related luminescent HAP materials on bone regeneration. In this work, we systematically investigated the bone regeneration pathway induced by nanostructured particles using defect-related luminescent hydroxyapatite (S2) materials. We monitored the subcellular distribution and location of S2 during osteoblast differentiation with the property of defect-related luminescence. Nano-scale S2 could be internalized by osteoblasts (OBs) via caveolae-mediated endocytosis and macropinocytosis. S2 incorporated into the lysosomes dissolved and released calcium ions for the formation of mineralized nodules. Extracellular S2 also promoted bone regeneration as a nucleation site. Taken together, the physical properties of hydroxyapatite control the bone regeneration pathway in osteoblasts.

Hydroxyapatite (HAP) is a widely used biomaterial for bone tissue substitution due to its chemical similarity with the natural bone.     

Zein as a versatile biopolymer: different shapes for different biomedical applications

In recent years, the interest regarding the use of proteins as renewable resources has deeply intensified. The strongest impact of these biomaterials is clear in the field of smart medicines and biomedical engineering. Zein, a vegetal protein extracted from corn, is a suitable biomaterial for all the above-mentioned purposes due to its biodegradability and biocompatibility. The controlled drug delivery of small molecules, fabrication of bioactive membranes, and 3D assembly of scaffold for tissue regeneration are just some of the topics now being extensively investigated and reported in the literature. Herein, we review the recent literature on zein as a biopolymer and its applications in the biomedical world, focusing on the different shapes and sizes through which it can be manipulated.

Zein a versatile biomaterial in the biomedical field. Easy to chemically functionalize with good emulsification properties, can be employed in drug delivery, fabrication of bioactive membranes and 3D scaffolds for tissue regeneration.     

A novel lamellar structural biomaterial and its effect on bone regeneration

To evaluate a novel lamellar structural biomaterial as a potential biomaterial for guided bone regeneration, we describe the preparation of a collagen membrane with high mechanical strength and anti-enzyme degradation ability by using the multi-level structure of Ctenopharyngodon idella scales. The physical and chemical properties, in vitro degradation, biocompatibility, and in vivo osteogenic activity were preliminarily evaluated. In conclusion, it was shown that the multi-layered collagen structure material had sufficient mechanical properties, biocompatibility, and osteogenic ability. Meanwhile, it is also shown that there is a gap in current clinical needs, between the guided tissue regeneration membrane and the one being used. Therefore, this study provides useful insights into the efforts being made to design and adjust the microstructure to balance its mechanical properties, degradation rate, and osteogenic activity.

To evaluate a novel lamellar structural biomaterial for guided bone regeneration, we describe the preparation of a collagen membrane with high mechanical strength and anti-enzyme degradation ability using Ctenopharyngodon idella scales.     

Development of banana (Musa balbisiana) pseudo stem fiber as a surgical bio-tool to avert post-operative wound infections

The search to develop an ideal suture material encourages us to explore novel suture biomaterials with superior characteristics to the current commercially available products. Surgical sutures play a crucial role in the development of post-operative wound infection by acting as a substrate for biofilm formation which leads to dehisced wounds. In this context, the present invention meets this need by fabricating banana (Musa balbisiana) fibre into an advanced antimicrobials releasing suture biomaterial (BSc) for the prevention of post-operative wound infection. Suture material developed from banana pseudo stem fiber was impregnated with chloramphenicol, clotrimazole and growth factors with the aid of a hydro-gel system. The fabricated suture material was found to be biocompatible towards human erythrocytes and L929 mouse fibroblast cells. BSc exhibited promising physico-chemical characteristics which were comparable to the commercially available Bombyx mori silk fibroin (BMSF) suture. BSc displayed a biphasic release pattern with sustained release of chloramphenicol for up to 140 h. Apart from being environment friendly and having a facile fabrication method, this advanced suture biomaterial showed broad spectrum in vitro antimicrobial activity against bacterial and fungal pathogens. BSc successfully impeded biofilm formation on its surface, as is evident from the confocal microscopy analysis. This contributes to superior wound healing efficacy in terms of reduced microbial burden and a subsequent decrease in the inflammatory cytokine levels. Histopathological observations further supported the pronounced healing efficacy of BSc sutured wounds. The findings of this study establish the banana pseudo stem fiber as a novel advanced suture biomaterial to prevent post-operative wound infections.

A novel antimicrobial suture biomaterial developed from banana waste fibers to avert post operative wound infections.     

Controlling the adsorption of osteopontin for mediating cell behaviour by using self-assembled monolayers with varying surface chemistry

Osteopontin (OPN) is an important protein for mediating cell behaviour on biomaterials. However, the interactions between the chemical groups on the biomaterial surface and OPN still need to be further clarified, which has restricted the application of OPN in biomaterial functionalization. In the present study, we developed different self-assembled monolayers (SAMs) with specific chemical groups, including SAMs-OH, SAMs-OEG, SAMs-COOH, SAMs-NH₂, and SAMs-PO₃H₂, to study the behavior of OPN on these SAMs. The results showed that SAMs-NH₂ could strongly adsorb OPN, and the amount of protein was highest on this material. Meanwhile, the lowest amount of OPN was present on SAMs-OEG. Interestingly, the unit-mass trend of bound OPN monoclonal antibodies (mAbs) on the SAMs was opposite to the OPN adsorption trend: lowest on SAMs-NH₂ but highest on SAMs-OEG. In vitro cell assay results showed that mouse bone marrow mesenchymal stem cells (mBMSCs) on SAMs-COOH, SAMs-NH₂, and SAMs-PO₃H₂ with pre-adsorbed OPN showed promoted behaviour, in terms of spreading, viability, and the expression levels of α_v and β₃ genes, compared with the other two SAMs, demonstrating the higher bioactivity of the adsorbed OPN. We believe that our findings will have great potential for developing OPN-activated biomaterials.

Osteopontin (OPN) is an important protein for mediating cell behaviour on biomaterials.     

Evolutionary approaches in protein engineering towards biomaterial construction

The tailoring of proteins for specific applications by evolutionary methods is a highly active area of research. Rational design and directed evolution are the two main strategies to reengineer proteins or create chimeric structures. Rational engineering is often limited by insufficient knowledge about proteins'' structure–function relationships; directed evolution overcomes this restriction but poses challenges in the screening of candidates. A combination of these protein engineering approaches will allow us to create protein variants with a wide range of desired properties. Herein, we focus on the application of these approaches towards the generation of protein biomaterials that are known for biodegradability, biocompatibility and biofunctionality, from combinations of natural, synthetic, or engineered proteins and protein domains. Potential applications depend on the enhancement of biofunctional, mechanical, or other desired properties. Examples include scaffolds for tissue engineering, thermostable enzymes for industrial biocatalysis, and other therapeutic applications.

Construction of versatile biomaterials is simplified by expanding the toolbox of protein engineering approaches.     

Covalently functionalized poly(etheretherketone) implants with osteogenic growth peptide (OGP) to improve osteogenesis activity

Polyetheretherketone (PEEK), as the most promising implant material for orthopedics and dental applications, has bone-like stiffness, excellent fatigue resistance, X-ray transparency, and near absence of immune toxicity. However, due to biological inertness, its bone conduction and bone ingrowth performance is limited. The surface modification of PEEK is an option to overcome these shortcomings and retain most of its favorable properties, especially when excellent osseointegration is desired. In this study, a simple reaction procedure was employed to bind the osteogenic growth peptide (OGP) on the surface of PEEK materials by covalent chemical grafting to construct a bioactive interface. The PEEK surface was activated by N,N′-disuccinimidyl carbonate (DSC) after hydroxylation, and then OGP was covalently grafted with amino groups. The functionalized surface of PEEK samples were characterized by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR), water contact angle measurement and biological evaluation in vitro. OGP-functionalized PEEK surface significantly promoted the attachment, proliferation, alkaline phosphatase (ALP) activity and mineralization of pre-osteoblast cells (MC3T3-E1). The in vivo rat tibia implantation model is adopted and micro-CT analyses demonstrated that the OGP coating significantly promoted new bone formation around the samples. The in vitro and in vivo results reveal that the modification by covalent chemical functionalization with OGP on PEEK surface can augment new bone formation surrounding implants compared to bare PEEK and PEEK implant modified by covalently attached OGP is promising in orthopedic and dental applications.

Polyetheretherketone (PEEK), as the most promising implant material for orthopedics and dental applications, has bone-like stiffness, excellent fatigue resistance, X-ray transparency, and near absence of immune toxicity.     

A Col I and BCP ceramic bi-layer scaffold implant promotes regeneration in osteochondral defects

Osteochondral defects occur in the superficial cartilage region, intermediate calcified cartilage, and subchondral bone. Due to the limited regenerative capacity and complex zonal structure, it is critically difficult to develop strategies for osteochondral defect repair that could meet clinical requirements. In this study, type I collagen (Col I) and BCP ceramics were used to fabricate a new bi-layer scaffold for regeneration in osteochondral defects. The in vitro studies showed that the bi-layer scaffold provided special functions for cell migration, proliferation and secretion due to the layered scaffold structure. The in vivo results demonstrated that the bi-layered scaffold could effectively promote the regeneration of both the cartilage and the subchondral bone, and the newly formed cartilage layer, with a similar structure and thickness to the natural cartilaginous layer, could seamlessly integrate with the surrounding natural cartilage and regenerate an interface layer to mimic the native osteochondral structure.

A new bi-layer scaffold composed of Col I and BCP ceramic was prepared to regenerate osteochondral defect. The result demonstrated the bi-layer scaffold could effectively promote the regeneration of both the cartilage and the subchondral bone layer.     

Biological properties of calcium phosphate biomaterials for bone repair: a review

Bone defects are a common disease threatening the health of many people. Calcium phosphate (CaP) is an ideal bone substitutive material that is widely used for bone repair due to its excellent biological properties including osteoinductivity, osteoconductivity and biodegradability. For this reason, investigation of these properties and the effects of various influencing factors is vital for modulating calcium phosphate during the design process to maximally satisfy clinical requirements. In this study, the latest studies on the biological properties of CaP biomaterials, including hydroxyapatite (HA), tricalcium phosphate (TCP), and biphasic calcium phosphate (BCP), have been summarized. Moreover, recent advances on how these properties are altered by different factors are reviewed. Considering the limited mechanical strength of CaP materials, this study also reviews CaP composites with different materials as improvement measures. Finally, perspectives regarding future developments of CaP materials are also provided.

This article reviews the recent advances and various factors affecting the improvement of the biological properties of calcium phosphate for bone repair.     

Visible-light-responsive reduced graphene oxide/g-C3N4/TiO2 composite nanocoating for photoelectric stimulation of neuronal and osteoblastic differentiation

Restoration of nerve supply in newly formed bone is critical for bone defect repair. However, nerve regeneration is often overlooked when designing bone repair biomaterials. In this study, employing graphitic carbon nitride (g-C₃N₄) as a visible-light-driven photocatalyst and reduced graphene oxide (rGO) as a conductive interface, an rGO/g-C₃N₄/TiO₂ (rGO/CN/TO) ternary nanocoating with photoelectric conversion ability was fabricated on a Ti-based orthopedic implant for photoelectric stimulation of both bone and nerve repair. Compared with g-C₃N₄/TiO₂ (CN/TO) and TiO₂ nanocoatings, the ternary nanocoating exhibited stronger visible-light absorption as well as higher transient photocurrent density and open circuit potential under blue LED exposure. The improved photo-electrochemical properties of the ternary nanocoating were attributed to the enhanced separation of photogenerated carriers at the heterointerface. For the tested nanocoatings, introducing blue LED light irradiation enhanced MC3T3-E1 osteoblastic differentiation and neurite outgrowth of PC12 cells. Among them, the rGO/CN/TO nanocoating exerted the greatest enhancement. In a coculture system, PC12 cells on the ternary nanocoating released a higher amount of neurotransmitter calcitonin gene-related peptide (CGRP) under light irradiation, which in turn significantly enhanced osteoblastic differentiation. The results may provide a prospective approach for targeting nerve regeneration to stimulate osteogenesis when designing bone repair biomaterials.

rGO/g-C₃N₄/TiO₂ nanocoating was fabricated on Ti-based implant for photoelectric stimulation of bone and nerve repair. The ternary nanocoating exerted greater photoelectric effects on enhancing osteoblastic differentiation and neurite outgrowth.     

Design of graphenic nanocomposites containing chitosan and polyethylene glycol for spinal cord injury improvement

Advanced therapeutic strategies include the incorporation of biomaterials, which has been identified as an effective method in treating unsolved diseases, such as spinal cord injury. During the acute phase, cascade responses involving cystic cavitation, fibrous glial scar formation, and myelin-associated dissuasive accumulation occur in the microenvironment of the spinal cord lesion. Graphene oxide (GO)-based materials, due to their extraordinary chemical, electrical and mechanical properties and easy to modify structure, are considered as rising stars in biomaterial and tissue engineering. In order to enhance the biodegradability and biocompatibility of GO, cell proliferation may be appropriately designed and situated at the lesion site. In this study, chitosan (CS) and polyethylene glycol (PEG) were grafted onto GO sheets. CS is a natural non-toxic polymer with good solubility and high biocompatible potential that has been used as an anti-inflammatory and anti-oxidant agent. Furthermore, PEG, a synthetic neuroprotective polymer, was used to develop the pharmacokinetic activity and reduce the toxicity of GO. Herein we report a novel nanocomposite consisting of PEG and CS with a potential advantage in spinal tissue regeneration. The preliminary in vitro study on mesenchymal stem cells (MSCs) has demonstrated that the prepared nanocomposites are not only non-toxic but also increase (by nearly 10%) cell growth. Finally, the use of mixed nanocomposites in the spinal cord injury (SCI) model resulted in good repair and inflammation decline after two weeks, such that walking and functional recovery scores of the hind limbs of mice were improved by an average of 6 points in the treatment group.

Herein we report a novel nanocomposite consisting of PEG and CS with a potential advantage in spinal tissue regeneration.     

Polydopamine functionalized VEGF gene-activated 3D printed scaffolds for bone regeneration

Bone is a highly vascularized organ and the formation of new blood vessels is essential to regenerate large critical bone defects. In this study, polylactic acid (PLA) scaffolds of 20–80% infill were three-dimensionally (3D) printed using a fused deposition modeling based 3D printer. The PLA scaffolds were coated with polydopamine (PDA) and then were surface-functionalized with polyethyleneimine (PEI) and VEGF-encoding plasmid DNA (pVEGF) nanoplexes (PLA-PDA-PEI-pVEGF). The PLA-PDA-PEI-pVEGF scaffolds with 40% infill demonstrated higher encapsulation efficiency and sustained release of pVEGF than scaffolds with 20, 60 and 80% infill and were therefore used for in vitro and in vivo studies. The PLA-PDA-PEI-pVEGF increased the translation and secretion of VEGF and BMP-2. The PLA-PDA-PEI-pVEGF also yielded a 2- and 4.5-fold change in VEGF and osteocalcin gene expression in vitro, respectively. A tube formation assay using human umbilical vascular endothelial cells (HUVECs) showed a significant increase in tube length when exposed to the PLA-PDA-PEI-pVEGF scaffold, in comparison to PLA and PLA-PDA scaffolds. The PLA-PDA-PEI-pVEGF scaffold in an in vivo rat calvarial critical bone defect model demonstrated 1.6-fold higher new bone formation compared to the PLA-PDA scaffold. H&E and Masson''s trichrome staining of bone sections also revealed that the PLA-PDA-PEI-pVEGF scaffold facilitated the formation of more blood vessels in the newly formed bone compared to the PLA and PLA-PDA scaffold groups. Thus, PLA-PDA-PEI-pVEGF might be a potential 3D printed gene activated scaffold for bone regeneration in clinical situations.

Bone is a highly vascularized organ and the formation of new blood vessels is essential to regenerate large critical bone defects.     

Inorganic process for wet silica-doping of calcium phosphate

Silica is not only a biocompatible trace element but also an essential element for bone formation and metabolism. Therefore, it is often doped into bioceramics such as calcium phosphate and calcium carbonate for enhancing biomaterial ability. Heretofore, organic silica materials are employed as silica sources, but the residual organic matter is a significant drawback in biomaterial applications. Therefore, in this study, we introduce a one-pot inorganic synthesis method for the formation of silica-doped octacalcium phosphate (OCP) using Na₂SiO₃ as the silica source. Silica was intercalated into the OCP unit lattice, replacing its hydrous layer structure, and then a layer-by-layer structure of apatite and silica was formed. Furthermore, by immersing the fabricated silica-doped OCP into suitable solutions, both silica-doped hydroxyapatite and carbonate apatite were fabricated through a one-step inorganic processes.

We introduced a one-pot synthesis method for silica doping of calcium phosphate. Silica easily incorporated into OCP interlayer optimizing Na₂SiO₃ concentrations.     

Icariin controlled release on a silk fibroin/mesoporous bioactive glass nanoparticles scaffold for promoting stem cell osteogenic differentiation

The treatment of bone defects caused by various reasons is still a major problem in orthopedic clinical work. Many studies on osteogenic implant materials have used various biologically active factors such as osteogenic inducers, but these biologically active factors have various side effects. Therefore, in this study, silk fibroin (SF) was used as a scaffold material, mesoporous bioactive glass nanoparticles (MBGNs) as a sustained release carrier, and the traditional Chinese drug icariin (ICA) was loaded to promote bone formation. The experiments in this study have proven that SF/MBGNs-ICA scaffolds can successfully load and release ICA for a long time, and the sustained-release ICA can promote the proliferation and differentiation of BMSCs for a long time. This controlled-release ICA organic/inorganic two-component scaffold material is expected to become a new bone grafting solution.

Long-term promotion of osteogenic differentiation through silk fibroin/mesoporous bioactive glass-loaded sustained release of icariin.     

The enhanced osteogenesis and osteointegration of 3-DP PCL scaffolds via structural and functional optimization using collagen networks

Optimal balance between biological activity and mechanical stability should be meticulously considered during scaffold design for bone tissue engineering applications. To fabricate an individualized construct with biomechanical and biological functionality for bone tissue regeneration, a polycaprolactone–collagen (PCL–COL) composite construct was developed through the combination of three-dimensional printing (3-DP) technology and biomimetic collagen matrix incorporation, with a 3-DP PCL framework maintaining the mechanical stability and a porous collagen matrix improving the biological activity. The results indicate that the compressive modulus of the composite constructs increased synergistically (over 40 MPa), providing sufficient mechanical support during new bone formation. On the other hand, the collagen matrix with a micro-porous architecture structurally increased scaffold areas and provided cellular adhesion sites, allowing for the functional construction of a favorable 3D microenvironment for BMSC adhesion, proliferation and extracellular matrix production. Moreover, critical-sized long bone defect (CSD) implantation demonstrated that the optimized composite constructs could promote bone tissue regeneration (5.5-fold) and bone-material osteointegration (4.7-fold), and decrease fibrosis encapsulation, compared to pristine PCL. The results indicate that these biomimetically ornamented PCL–COL constructs exhibit favorable mechanical properties and biological functionality, demonstrating great potential as an effective bone graft substitute for bone defect treatment. Meanwhile, they can also harness the advantages of 3-DP technology and a collagen-based functionalized strategy, facilitating the creation of customized and functional PCL–COL constructs for clinical translation.

Optimal balance between biological activity and mechanical stability should be meticulously considered during scaffold design for bone tissue engineering applications.     

Biomaterials for bone tissue engineering scaffolds: a review

Bone tissue engineering has been continuously developing since the concept of “tissue engineering” has been proposed. Biomaterials that are used as the basic material for the fabrication of scaffolds play a vital role in bone tissue engineering. This paper first introduces a strategy for literature search. Then, it describes the structure, mechanical properties and materials of natural bone and the strategies of bone tissue engineering. Particularly, it focuses on the current knowledge about biomaterials used in the fabrication of bone tissue engineering scaffolds, which includes the history, types, properties and applications of biomaterials. The effects of additives such as signaling molecules, stem cells, and functional materials on the performance of the scaffolds are also discussed.

Bone tissue engineering has been continuously developing since the concept of “tissue engineering” has been proposed. Biomaterials, as the basic material for the fabrication of scaffolds, play a vital role in bone tissue engineering.     

Biomaterials in myocardial tissue engineering

Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternative sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end‐stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augmenting injured or impaired myocardium, with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds – composed of natural or synthetic biomaterials or decellularized extracellular matrix – that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue; and finally, injectable biomaterials (hydrogels) designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post‐infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Fe/Zn-modified tricalcium phosphate (TCP) biomaterials: preparation and biological properties

Bone repairing materials play an essential role in the repair treatment of bone defects. The presence of calcium phosphate invertebrates is of significance for bone repairing processes. However, the mechanical properties and osteogenic activities of many current calcium phosphate materials are not ideal, which limit their biological applications. Therefore, it is an effective alternative strategy to study the modification of calcium phosphate biomaterials to address these limitations. In this research, in order to enhance the biological performance of tricalcium phosphate (β-TCP), metal species (Fe and Zn) modified β-TCP materials through the co-precipitation method were successfully developed. The physical, chemical and biological properties of the binary composites were carefully studied for the first time. The bioactivities of the Fe-TCP and Zn-TCP were evaluated by simulating body fluid (SBF) immersion experiments, blood compatibility, and cytotoxicity tests. The findings demonstrated that the metal-TCP with excellent cytocompatibility and osteogenic properties shows good potential in medical applications.

Fe/Zn-TCP biomaterials were prepared and their bioactivities to enhance the synthetic bone-repair materials were studied in comparison.