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Since their discovery, Black Phosphorus (BP)-based nanomaterials have received extensive attentions in the fields of electromechanics, optics and biomedicine, due to their remarkable properties and excellent biocompatibility. The most essential feature of BP is that it is composed of a single phosphorus element, which has a high degree of homology with the inorganic components of natural bone, therefore it has a full advantage in the treatment of bone defects. This review will first introduce the source, physicochemical properties, and degradation products of BP, then introduce the remodeling process of bone, and comprehensively summarize the progress of BP-based materials for bone therapy in the form of hydrogels, polymer membranes, microspheres, and three-dimensional (3D) printed scaffolds. Finally, we discuss the challenges and prospects of BP-based implant materials in bone immune regulation and outlook the future clinical application.

Objectives: Bone morphogenetic proteins (BMPs), more specifically BMP-2, are being increasingly used in orthopaedic surgery due to advanced research into osteoinductive factors that may enhance and improve bone therapy. There are many areas in therapy that BMP-2 is being applied to, including dental treatment, open tibial fractures, cancer and spinal surgery. Within these areas of treatment, there are many reports of successes and pitfalls. This review explores the use of BMP-2 and its successes, pitfalls and future prospects in bone therapy., Methods: The PubMed database was consulted to compile this review., Key Findings: With successes in therapy, there were descriptions of a more rapid healing time with no signs of rejection or infection attributed to BMP-2 treatment. Pitfalls included BMP-2 'off-label' use, which lead to various adverse effects., Conclusions: Our search highlighted that optimising treatment with BMP-2 is a direction that many researchers are exploring, with areas of current research interest including concentration and dose of BMP-2, carrier type and delivery., (© 2015 Royal Pharmaceutical Society.)

[Display omitted] Due to their prominent physicochemical properties, 2D materials are broadly applied in biomedicine. Currently, 2D materials have achieved great success in treating many diseases such as cancer and tissue engineering as well as bone therapy. Based on their different characteristics, 2D materials could function in various ways in different bone diseases. Herein, the application of 2D materials in bone tissue engineering, joint lubrication, infection of orthopedic implants, bone tumors, and osteoarthritis are firstly reviewed comprehensively together. Meanwhile, different mechanisms by which 2D materials function in each disease reviewed below are also reviewed in detail, which in turn reveals the versatile functions and application of 2D materials. At last, the outlook on how to further broaden applications of 2D materials in bone therapies based on their excellent properties is also discussed. [ABSTRACT FROM AUTHOR]

Purpose of Review: The main objective of this article is to investigate the current trends in the use of induced pluripotent stem cells (iPSCs) for bone tissue repair and regeneration., Recent Findings: Pluripotent stem cell-based tissue engineering has extended innovative therapeutic approaches for regenerative medicine. iPSCs have shown osteogenic differentiation capabilities and would be an innovative resource of stem cells for bone tissue regenerative applications. This review recapitulates the current knowledge and recent progress regarding utilization of iPSCs for bone therapy. A review of current findings suggests that a combination of a three-dimensional scaffolding system with iPSC technology to mimic the physiological complexity of the native stem cell niche is highly favorable for bone tissue repair and regeneration.

Osteoporosis affects the oral and maxillofacial parts which can cause an osteoporotic jawbone (OJB). Osteoporosis therapy can be through both surgical and non-surgical approaches. One of the effective and optimal alternative therapies needed for OJB therapy is, for example, the regenerative therapy. The concept of regenerative therapies involving the triad of tissue engineering such as cells, growth factors and biomaterials can be applied in OJB therapy by combining the injectable chitosan scaffold (ICS) as a biomaterial scaffold, concentrated growth factor (CGF) as a growth factor, and gingival mesenchymal stem cells (GMSCs) as medicinal signaling cells. The purpose of this review was to describe the future prospect of ICS, CGF, and GMSCs as regenerative osteoporotic jaw bone therapy. ICS is biocompatible and biodegradable and easy to apply. It has the osteoinductive, osteoconductive, and osteotemplate properties. While, GMSCs are chosen compared to other MSCs because they are easily available and proliferate faster than Bone Marrow-derived Stem Cells (BMSC) and Dental Pulp Stem Cells (DPSCs).Besides, CGF is picked because, it has more fibrin and growth factors (GF) than Platelet Rich Fibrin (PRF) and Platelet Rich Plasma (PRP). The combination of ICS, CGF and GMSC has the potential and promising therapy in treating OJB. [ABSTRACT FROM AUTHOR]

The increasing demand for effective bone regeneration materials drives the exploration of biomaterials with enhanced bioactivity and biocompatibility, such as zinc-substituted compounds. This study investigates the in vitro cellular interactions with nanostructured spheres composed of alginate/carbonated hydroxyapatite (CHA), compared to zinc-substituted CHA (ZnCHA). This work aimed to compare the physicochemical properties and biological effects of ZnCHA and CHA on osteoblasts. ZnCHA was synthesized using a wet chemical method, followed by characterization through X-ray diffraction, Fourier transform infrared spectroscopy, total organic carbon analysis, Wavelength-dispersive X-ray spectroscopy, and BET surface area analysis to assess ion release and structural changes. Biological evaluation was conducted using cell viability, proliferation, and biomineralization assays on osteoblasts. Results showed successful incorporation of zinc and carbonate, leading to reduced crystallinity and increased surface area. Cell viability and proliferation assays indicated ZnCHA's cytocompatibility and enhanced osteoblastic activity, with increased mineralization nodules compared to CHA samples. The study concludes that ZnCHA composites are promising candidates for bone tissue engineering, demonstrating improved cytocompatibility and potential for further preclinical evaluations. [ABSTRACT FROM AUTHOR]

Bone defect is a common clinical symptom which can arise from various causes. Currently, bone tissue engineering has demonstrated positive therapeutic effects for bone defect repair by using seeding cells such as mesenchymal stem cells and precursor cells. N-acetylcysteine (NAC) is a stable, safe and highly bioavailable antioxidant that shows promising prospects in bone tissue engineering due to the ability to attenuate oxidative stress and enhance the osteogenic potential and immune regulatory function of cells. This review systematically introduces the antioxidant mechanism of NAC, analyzes the advancements in NAC-related research involving mesenchymal stem cells, precursor cells, innate immune cells and animal models, discusses its function using the classic oral microenvironment as an example, and places particular emphasis on the innovative applications of NAC-modified tissue engineering biomaterials. Finally, current limitations and future prospects are proposed, with the aim of providing inspiration for targeted readers in the field. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles were shown to have similar functional roles to their parent cells without the defect of potential tumorigenicity, which made them a great candidate for regenerative medicine. The last twenty years have witnessed the rapid development of research on small extracellular vesicles. In this paper, we employed a scientometric synthesis method to conduct a retrospective analysis of small extracellular vesicles in the field of bone-related diseases. The overall background analysis consisted the visualization of the countries, institutions, journals, and authors involved in research. The current status of the research direction and future trends were presented through the analysis of references and keywords, which showed that engineering strategies, mesenchymal stem cell derived exosomes, and cartilage damage were the most concerning topics, and scaffold, osteoarthritis, platelet-rich plasma, and senescence were the future trends. We also discussed the current problems and challenges in practical applications, including the in-sight mechanisms, the building of relevant animal models, and the problems in clinical trials. By using CiteSpace, VOSviewer, and Bibliometrix, the presented data avoided subjective selectivity and tendency well, which made the conclusion more reliable and comprehensive. We hope that the findings can provide new perspectives for researchers to understand the evolution of this field over time and to search for novel research directions. [ABSTRACT FROM AUTHOR]

Bone regeneration using Bone Morphogenetic Proteins (BMPs) alongside various engineered scaffolds has attracted considerable attention over the years. The field has seen extensive research in preclinical animal models, leading to the approval of two products and guiding the quest for new materials. Natural and synthetic polymers, ceramics, and composites have been used to fabricate the necessary porous 3D scaffolds and delivery systems for BMPs. Interestingly, all reported applications in the literature are triumphant. Evaluation of the results is typically based on histologic assessment after appropriate staining and radiological modalities, providing morphological identification of the newly formed bone and describing cells and the organic compound. Remarkably, while these evaluation methods illustrate mineralization, they are not capable of identifying hydroxyapatite crystals, the mineral component of the bone, which are crucial for its mechanical properties, structure, integrity, and long-term stability of regenerated bone tissue. This review aims to focus on the different scaffolds used in bone tissue engineering applications and underline the pressing need for techniques that could recognize the presence of hydroxyapatite crystals as well as their characteristics in bone tissue engineering, which will provide a more complete and comprehensive assessment of the successful results. [ABSTRACT FROM AUTHOR]

Bone tissue engineering is pivotal in facilitating bone reconstruction by promoting persistent angiogenesis and osteogenesis. Initially, the hot gel composite hydrogel scaffold technique was employed. However, to address various limitations, numerous gel structures have since been developed, including osteogenic gellan gels, semi-interpenetrating network hydrogels, photoinduced crosslinking methacrylate gels, and supramolecular hydrogels. This review examines the mechanisms, formation principles, and medical benefits of these gel structures. In addition, novel bioengineering techniques to regulate human bone growth are expected to emerge in the future. This work is expected to significantly expedite the advancement of hydrogel membranes in the field of bone repair. Despite years of exploration, numerous challenges remain unresolved in the field of hydrogels and hydrogel membranes for bone repair. In this review, we provide a comprehensive overview of the fundamental principles and current development status of hydrogel materials for bone repair, including their mechanisms, formation principles, and medical benefits in bone regeneration. Additionally, we summarize recent effective strategies to develop advanced hydrogels and technical approaches for bone repair while also discussing future directions. [ABSTRACT FROM AUTHOR]

Bone Morphogenetic Proteins (BMPs) are multifunctional secreted cytokines, which belong to the TGF-β superfamily. These glycoproteins act as a disulfide-linked homo- or heterodimers, being potent regulators of bone and cartilage formation and repair, cell proliferation during embryonic development and bone homeostasis in the adult. BMPs are promising molecules for tissue engineering and bone therapy. The present review discusses this family of proteins, their structure and biological function, their therapeutic applications and drawbacks, their effects on mesenchymal stem cells differentiation, and the cell signaling pathways involved in this process., (Copyright © 2014. Published by Elsevier Inc.)

Recently, nanotechnologies have become increasingly prominent in the field of bone tissue engineering (BTE), offering substantial potential to advance the field forward. These advancements manifest in two primary ways: the localized application of nanoengineered materials to enhance bone regeneration and their use as nanovehicles for delivering bioactive compounds. Despite significant progress in the development of bone substitutes over the past few decades, it is worth noting that the quest to identify the optimal biomaterial for bone regeneration remains a subject of intense debate. Ever since its initial discovery, poly(lactic-co-glycolic acid) (PLGA) has found widespread use in BTE due to its favorable biocompatibility and customizable biodegradability. This review provides an overview of contemporary advancements in the development of bone regeneration materials using PLGA polymers. The review covers some of the properties of PLGA, with a special focus on modifications of these properties towards bone regeneration. Furthermore, we delve into the techniques for synthesizing PLGA nanoparticles (NPs), the diverse forms in which these NPs can be fabricated, and the bioactive molecules that exhibit therapeutic potential for promoting bone regeneration. Additionally, we addressed some of the current concerns regarding the safety of PLGA NPs and PLGA-based products available on the market. Finally, we briefly discussed some of the current challenges and proposed some strategies to functionally enhance the fabrication of PLGA NPs towards BTE. We envisage that the utilization of PLGA NP holds significant potential as a potent tool in advancing therapies for intractable bone diseases. [ABSTRACT FROM AUTHOR]

Infected bone defects represent a common clinical condition involving bone tissue, often necessitating surgical intervention and antibiotic therapy. However, conventional treatment methods face obstacles such as antibiotic resistance and susceptibility to postoperative infections. Hydrogels show great potential for application in the field of tissue engineering due to their advantageous biocompatibility, unique mechanical properties, exceptional processability, and degradability. Recent interest has surged in employing hydrogels as a novel therapeutic intervention for infected bone repair. This article aims to comprehensively review the existing literature on the anti-microbial and osteogenic approaches utilized by hydrogels in repairing infected bones, encompassing their fabrication techniques, biocompatibility, antimicrobial efficacy, and biological activities. Additionally, the potential opportunities and obstacles in their practical implementation will be explored. Lastly, the limitations presently encountered and the prospective avenues for further investigation in the realm of hydrogel materials for the management of infected bone defects will be deliberated. This review provides a theoretical foundation and advanced design strategies for the application of hydrogel materials in the treatment of infected bone defects. [ABSTRACT FROM AUTHOR]

Nano-hydroxyapatite (HAp) is an ideal material in the field of biomedicine due to its good biocompatibility and bioactivity. However, a significant drawback of pure HAp materials is their inferior mechanical properties. Therefore, in this rigorous investigation, the optimal calcium-to-phosphorus ratio for the synthesis of HAp was meticulously delineated, followed by its nuanced modification using KH550 (γ-aminopropyltriethoxysilane). This was further amalgamated with polycaprolactone (PCL) with the aim of providing a superior material alternative within the domain of bone scaffold materials. The post-modified HAp demonstrated enhanced interfacial compatibility with PCL, bestowing the composite with superior mechanical characteristics, notably a peak bending strength of 6.38 ± 0.037 MPa and a tensile strength of 3.71 ± 0.040 MPa. Scanning electron microscope (SEM) imagery revealed an intriguing characteristic of the composite: an initial ascension in porosity upon HAp integration, subsequently followed by a decline. Beyond this, the composite not only exhibited stellar auto-degradation prowess but also realized a sustained release cycle of 24 h, markedly optimizing drug utility efficiency. A kinetic model for drug dispensation was developed, positing an adherence to a pseudo-second-order kinetic principle. In tandem, through the formulation of an intra-particle diffusion model, the diffusion mechanisms pre- and post-modification were deeply probed. Cytotoxicity assays underscored the composite's exemplary biocompatibility. Such findings accentuate the vast potential of the modified HAp–PCL composite in bone tissue engineering, heralding a novel and efficacious avenue for impending bone defect amelioration. [ABSTRACT FROM AUTHOR]

Improvements in Tissue Engineering and Regenerative Medicine (TERM)–type technologies have allowed the development of specific materials that, together with a better understanding of bone tissue structure, have provided new pathways to obtain biomaterials for bone tissue regeneration. In this manuscript, bioabsorbable materials are presented as emerging materials in tissue engineering therapies related to bone lesions because of their ability to degrade in physiological environments while the regeneration process is completed. This comprehensive review aims to explore the studies, published since its inception (2010s) to the present, on bioabsorbable composite materials based on PLA and PCL polymeric matrix reinforced with Mg, which is also bioabsorbable and has recognized osteoinductive capacity. The research collected in the literature reveals studies based on different manufacturing and dispersion processes of the reinforcement as well as the physicochemical analysis and corresponding biological evaluation to know the osteoinductive capacity of the proposed PLA/Mg and PCL/Mg composites. In short, this review shows the potential of these composite materials and serves as a guide for those interested in bioabsorbable materials applied in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Aerogels are fascinating solid materials known for their highly porous nanostructure and exceptional physical, chemical, and mechanical properties. They show great promise in various technological and biomedical applications, including tissue engineering, and bone and cartilage substitution. To evaluate the bioactivity of bone substitutes, researchers typically conduct in vitro tests using simulated body fluids and specific cell lines, while in vivo testing involves the study of materials in different animal species. In this context, our primary focus is to investigate the applications of different types of aerogels, considering their specific materials, microstructure, and porosity in the field of bone and cartilage tissue engineering. From clinically approved materials to experimental aerogels, we present a comprehensive list and summary of various aerogel building blocks and their biological activities. Additionally, we explore how the complexity of aerogel scaffolds influences their in vivo performance, ranging from simple single-component or hybrid aerogels to more intricate and organized structures. We also discuss commonly used formulation and drying methods in aerogel chemistry, including molding, freeze casting, supercritical foaming, freeze drying, subcritical, and supercritical drying techniques. These techniques play a crucial role in shaping aerogels for specific applications. Alongside the progress made, we acknowledge the challenges ahead and assess the near and far future of aerogel-based hard tissue engineering materials, as well as their potential connection with emerging healing techniques. [ABSTRACT FROM AUTHOR]

Biological macromolecules like polysaccharides/proteins/glycoproteins have been widely used in the field of tissue engineering due to their ability to mimic the extracellular matrix of tissue. In addition to this, these macromolecules are found to have higher biocompatibility and no/lesser toxicity when compared to synthetic polymers. In recent years, scaffolds made up of proteins, polysaccharides, or glycoproteins have been highly used due to their tensile strength, biodegradability, and flexibility. This review is about the fabrication methods and applications of scaffolds made using various biological macromolecules, including polysaccharides like chitosan, agarose, cellulose, and dextran and proteins like soy proteins, zein proteins, etc. Biopolymer-based nanocomposite production and its application and limitations are also discussed in this review. This review also emphasizes the importance of using natural polymers rather than synthetic ones for developing scaffolds, as natural polymers have unique properties, like high biocompatibility, biodegradability, accessibility, stability, absence of toxicity, and low cost. [ABSTRACT FROM AUTHOR]

Hydrogels, also known as three-dimensional, flexible, and polymer networks, are composed of natural and/or synthetic polymers with exceptional properties such as hydrophilicity, biocompatibility, biofunctionality, and elasticity. Researchers in biomedicine, biosensing, pharmaceuticals, energy and environment, agriculture, and cosmetics are interested in hydrogels. Hydrogels have limited adaptability for complicated biological information transfer in biomedical applications due to their lack of electrical conductivity and low mechanical strength, despite significant advances in the development and use of hydrogels. The nano-filler-hydrogel hybrid system based on supramolecular interaction between host and guest has emerged as one of the potential solutions to the aforementioned issues. Black phosphorus, as one of the representatives of novel two-dimensional materials, has gained a great deal of interest in recent years owing to its exceptional physical and chemical properties, among other nanoscale fillers. However, a few numbers of publications have elaborated on the scientific development of black phosphorus hybrid hydrogels extensively. In this review, this review thus summarized the benefits of black phosphorus hybrid hydrogels and highlighted the most recent biological uses of black phosphorus hybrid hydrogels. Finally, the difficulties and future possibilities of the development of black phosphorus hybrid hydrogels are reviewed in an effort to serve as a guide for the application and manufacture of black phosphorus -based hydrogels. Recent applications of black phosphorus hybrid hydrogels in biomedicine. [ABSTRACT FROM AUTHOR]

Tissue engineering is approach of replacing or regeneration of biological functions of tissues or organs by using combination of biomaterials, biomolecules and cells. Tissue engineering mainly depends scaffold biomaterials and scaffold fabrication methods. Therefore, there have been progressive investigation and development of new biomaterials with different formulations to help and achieve necessary requirements in the tissue engineering applications. This review is briefly representing necessary features associated with biomaterial type and design required for tissue regeneration applications, and presenting earlier research in tissue engineering field and new trends for future implementation. It is mainly focusing on generations of biomaterials and discovery tissue engineering field. As well as, different types of biomaterials, such as bioceramics, bioactive glasses, synthetic and natural polymers and their derived composites, used in fabrication of scaffolds (as a main part of tissue engineering) are demonstrated in this review. Scaffold fabrication methods are also reviewed here. Moreover, it is showing the recent achievements in tissue engineering field for bone, skin, cartilage, neural, and cardiac regeneration as a pre-clinical procedure for repair of injured and diseased tissues and organs. Finally, recent trends and challenges of biomaterials for tissue regeneration are presented also in this review. [ABSTRACT FROM AUTHOR]

In recent decades, bone tissue engineering, which is supported by scaffold, seed cells and bioactive molecules (BMs), has provided new hope and direction for treating bone defects. In terms of seed cells, compared to bone marrow mesenchymal stem cells, which were widely utilized in previous years, adipose-derived stem cells (ADSCs) are becoming increasingly favored by researchers due to their abundant sources, easy availability and multi-differentiation potentials. However, there is no systematic theoretical basis for selecting appropriate biomaterials loaded with ADSCs. In this review, the regulatory effects of various biomaterials on the behavior of ADSCs are summarized from four perspectives, including biocompatibility, inflammation regulation, angiogenesis and osteogenesis, to illustrate the potential of combining various materials with ADSCs for the treatment of bone defects. In addition, we conclude the influence of additional application of various BMs on the bone repair effect of ADSCs, in order to provide more evidences and support for the selection or preparation of suitable biomaterials and BMs to work with ADSCs. More importantly, the associated clinical case reports and experiments are generalized to provide additional ideas for the clinical transformation and application of bone tissue engineering loaded with ADSCs. [ABSTRACT FROM AUTHOR]

Critical-sized bone defects are always difficult to treat, and they are associated with a significant burden of disease in clinical practice. In recent decades, due to the fast development of biomaterials and tissue engineering, many bioinspired materials have been developed to treat large bone defects. Due to the excellent osteoblastic ability of black phosphorous (BP), many BP-based biomaterials have been developed to treat bone defects. Therefore, there are abundant studies as well as a tremendous amount of research data. It is urgent to conduct evidence-based research to translate these research data and results into validated scientific evidence. Therefore, in our present study, a qualitative systematic review and a quantitative meta-analysis were performed. Eighteen studies were included in a systematic review, while twelve studies were included in the meta-analysis. Our results showed that the overall quality of experimental methods and reports of biomaterials studies was still low, which needs to be improved in future studies. Besides, we also proved the excellent osteoblastic ability of BP-based biomaterials. But we did not find a significant effect of near-infrared (NIR) laser in BP-based biomaterials for treating bone defects. However, the quality of the evidence presented by included studies was very low. Therefore, to accelerate the clinical translation of BP-based biomaterials, it is urgent to improve the quality of the study method and reporting in future animal studies. More evidence-based studies should be conducted to enhance the quality and clinical translation of BP-based biomaterials. [ABSTRACT FROM AUTHOR]

Recently, research on and the application of nanomaterials such as graphene, carbon nanotubes, and metal–organic frameworks has become increasingly popular in tissue engineering. In 2014, a two-dimensional sheet of black phosphorus (BP) was isolated from massive BP crystals. Since then, BP has attracted significant attention as an emerging nanomaterial. BP possesses many advantages such as light responsiveness, electrical conductivity, degradability, and good biocompatibility. Thus, it has broad prospects in biomedical applications. Moreover, BP is composed of phosphorus, which is a key bone tissue component with good biocompatibility and osteogenic repair ability. Thereby, BP exhibits excellent advantages for application in bone tissue engineering. In this review, the structure and the physical and chemical properties of BP are described. In addition, the current applications of BP in bone tissue engineering are reviewed to aid the future research and application of BP. [ABSTRACT FROM AUTHOR]

In our aging society, the number of patients suffering from poorly healing bone defects increases. Bone morphogenetic proteins (BMPs) are used in the clinic to promote bone regeneration. However, poor control of BMP delivery and thus activity necessitates high doses, resulting in adverse effects and increased costs. It has been demonstrated that messenger RNA (mRNA) provides a superior alternative to protein delivery due to local uptake and prolonged expression restricted to the site of action. Here, we present the development of porous collagen scaffolds incorporating peptide-mRNA nanoparticles (NPs). Nanoparticles were generated by simply mixing aqueous solutions of the cationic cell-penetrating peptide PepFect14 (PF14) and mRNA. Peptide-mRNA complexes were uniformly distributed throughout the scaffolds, and matrices fully preserved cell attachment and viability. There was a clear dependence of protein expression on the incorporated amount of mRNA. Importantly, after lyophilization, the mRNA formulation in the collagen scaffolds retained activity also at 4 °C over two weeks. Overall, our results demonstrate that collagen scaffolds incorporating peptide-mRNA complexes hold promise as off-the-shelf functional biomaterials for applications in regenerative medicine and constitute a viable alternative to lipid-based mRNA formulations. [ABSTRACT FROM AUTHOR]

Facilitated endogenous tissue engineering, as a facile and effective strategy, is emerging for use in bone tissue regeneration. However, the development of bioactive scaffolds with excellent osteo-inductivity to recruit endogenous stem cells homing and differentiation towards lesion areas remains an urgent problem. Chitosan (CS), with versatile qualities including good biocompatibility, biodegradability, and tunable physicochemical and biological properties is undergoing vigorously development in the field of bone repair. Based on this, the review focus on recent advances in chitosan-based scaffolds for facilitated endogenous bone regeneration. Initially, we introduced and compared the facilitated endogenous tissue engineering with traditional tissue engineering. Subsequently, the various CS-based bone repair scaffolds and their fabrication methods were briefly explored. Furthermore, the functional design of CS-based scaffolds in bone endogenous regeneration including biomolecular loading, inorganic nanomaterials hybridization, and physical stimulation was highlighted and discussed. Finally, the major challenges and further research directions of CS-based scaffolds were also elaborated. We hope that this review will provide valuable reference for further bone repair research in the future. [ABSTRACT FROM AUTHOR]

This study aims to design a 3D carbonate-hydroxyapatite (CHA)/sago (S) based egg white (EW) microstructure with antibacterial properties to improve the performance of bone grafts for bone tissue engineering. In this study, Pinctada maxima (P. maxima) shell was used as a calcium (Ca) source in CHA synthesis. The annealing temperature of CHA at 900, 1000, and 1100 °C affected microstructural and lattice parameters, with stoichiometry 1.72–1.77, and B-type CHA was identified. CHA/S with various concentrations of EW (10 and 30 wt.%) effectively increased pore size and porosity. XRD spectra confirmed that sago and EW in CHA nanocomposite stable the crystal structure. FTIR spectrum shows protein phosphorylation in CHA nanocomposite due to PO43− ion exchange. In-vitro bioactivity of CHA-S10 (MTT assay) showed increased cell viability and optical density (OD; 24–48 h) to control. Antibacterial activity of CHA-S10 and CHA/S (control) against bacteria associated with periodontal disease and bone infection (Actinobacillus actinomycetemcomitans [A. actinomycetemcomitans], Porphyromonas gingivalis [P. gingivalis], Fusobacterium nucleatum [F. nucleatum; gram negative], and Staphylococcus aureus [S. aureus; gram positive]) by disc diffusion method showed that CHA-S10 and CHA/S had strong antibacterial activity. In conclusion, EW's properties had proven the CHA/S/EW as bone grafts, effectively increasing pore size, porosity, biocompatibility, and strong antibacterial properties. [ABSTRACT FROM AUTHOR]

Modern biomedicine aims to develop integrated solutions that use medical, biotechnological, materials science, and engineering concepts to create functional alternatives for the specific, selective, and accurate management of medical conditions. In the particular case of tissue engineering, designing a model that simulates all tissue qualities and fulfills all tissue requirements is a continuous challenge in the field of bone regeneration. The therapeutic protocols used for bone healing applications are limited by the hierarchical nature and extensive vascularization of osseous tissue, especially in large bone lesions. In this regard, nanotechnology paves the way for a new era in bone treatment, repair and regeneration, by enabling the fabrication of complex nanostructures that are similar to those found in the natural bone and which exhibit multifunctional bioactivity. This review aims to lay out the tremendous outcomes of using inorganic nanoparticles in bone healing applications, including bone repair and regeneration, and modern therapeutic strategies for bone-related pathologies. [ABSTRACT FROM AUTHOR]

The constant evolution and advancement of the biomedical field requires robust and innovative research. Two-dimensional nanomaterials are an emerging class of materials that have risen the attention of the scientific community. Their unique properties, such as high surface-to-volume ratio, easy functionalization, photothermal conversion, among others, make them highly versatile for a plethora of applications ranging from energy storage, optoelectronics, to biomedical applications. Recent works have proven the efficiency of 2D nanomaterials for cancer photothermal therapy (PTT), drug delivery, tissue engineering, and biosensing. Combining these materials with hydrogels and scaffolds can enhance their biocompatibility and improve treatment for a variety of diseases/injuries. However, given that the use of two-dimensional nanomaterials-based polymeric composites for biomedical applications is a very recent subject, there is a lot of scattered information. Hence, this review gathers the most recent works employing these polymeric composites for biomedical applications, providing the reader with a general overview of their potential. [ABSTRACT FROM AUTHOR]

Bone grafts or prosthetic implant designing for clinical application is challenging due to the complexity of integrated physiological processes. The revolutionary advances of nanotechnology in the biomaterial field expedite and endorse the current unresolved complexity in functional bone graft and implant design. Rare earth (RE) materials are emerging biomaterials in tissue engineering due to their unique biocompatibility, fluorescence upconversion, antimicrobial, antioxidants, and anti‐inflammatory properties. Researchers have developed various RE smart nano‐biomaterials for bone tissue engineering and implantology applications in the past two decades. Furthermore, researchers have explored the molecular mechanisms of RE material‐mediated tissue regeneration. Recent advances in biomedical applications of micro or nano‐scale RE materials have provided a foundation for developing novel, cost‐effective bone tissue engineering strategies. This review attempted to provide an overview of RE nanomaterials' technological innovations in bone tissue engineering and implantology and summarized the osteogenic, angiogenic, immunomodulatory, antioxidant, in vivo bone tissue imaging, and antimicrobial properties of various RE nanomaterials, as well as the molecular mechanisms involved in these biological events. Further, we extend to discuss the challenges and prospects of RE smart nano‐biomaterials in the field of bone tissue engineering and implantology. [ABSTRACT FROM AUTHOR]

Biomaterials are a large group of vitally important materials with many different inorganic and organic types. Biocomposites are produced by using materials such as polymer, metal, and ceramics. Bone tissue engineering deals with materials that can mimic the real bone structure found in the body. These materials used in the human body must be capable of many aspects such as their mechanical strength related to the area where they are used, as well as their properties such as biocompatible, biodegradable, and non-toxic. If the material is intended to treat the bone structure, it should be biodegradable, but it should be resistant to degradation if intended to be used for a long time. With the advance in technology, nanoparticles have become appealing in bone tissue engineering due to their many unique properties. In recent years, mesoporous silica nanoparticles (MSNs) have been prominent biomaterials in the medical field due to their properties such as alterable size structure, large pore volume, and surface area. This study aims to give information about the biomedical properties, synthesis methods, and importance of MSNs with unique properties in bone tissue engineering applications. This study is compiled by examining many studies in the literature. [ABSTRACT FROM AUTHOR]

Recently, several types of native tissues have been enzymatically digested to prepare hydrogels that have natural‐mimic extracellular matrix (ECM) proteins, architecture, and biologic activities. However, the residual detergents and salts remaining in the hydrogel may cause some undesirable effects on compatibility, functionality, and bioactivity of the material. In this study, we enzymatically digested the demineralized and decellularized bone matrix (DDBM) and adopted two common methods that included dialysis against distilled water and acetone precipitation for sample desalting. Efficiency in salt removal, protein preservation, gelation ability, and in vivo biocompatibility and function were compared to the DDBM digest without a desalting treatment. After lyophilization, the dialyzed, precipitated, and non‐desalted DDBM digests all exhibited cotton‐like texture and were water‐soluble; however, only the precipitated DDBM digest could be gelled. We also found that the method of acetone precipitation could effectively remove salt from the DDBM digest while preserving of multiple proteins from the native bone and internal porous structure. A total of 57 proteins were identified by mass spectrometry in the precipitated DDBM digest and the majority of these proteins are critical to overall protein assembly, scaffold structure and stability, and cell‐activities. Additionally, the precipitated DDBM digest possessed enhanced biocompatibility and osteointegration in repairing a cranial bone defect in Sprague–Dawley (SD) rat. In conclusion, the soluble, biodegradable, and biocompatible natures of the precipitated DDBM digest allow its usage in bone tissue engineering as a protein carrier because of its resemblance to native bone‐like protein composite and operative flexibility. [ABSTRACT FROM AUTHOR]

To date, nanotechnology has increasingly been identified as a promising and efficient means to address a number of challenges associated with public health. In the past decade, two-dimensional (2D) biomaterials, as a unique nanoplatform with planar topology, have attracted explosive interest in various fields such as biomedicine due to their unique morphology, physicochemical properties and biological effect. Motivated by the progress of graphene in biomedicine, dozens of types of ultrathin 2D biomaterials have found versatile bio-applications, including biosensing, biomedical imaging, delivery of therapeutic agents, cancer theranostics, tissue engineering, as well as others. The effective utilization of 2D biomaterials stems from the in-depth knowledge of structure–property–bioactivity–biosafety–application–performance relationships. A comprehensive summary of 2D biomaterials for biomedicine is still lacking. In this comprehensive review, we aim to concentrate on the state-of-the-art 2D biomaterials with a particular focus on their versatile biomedical applications. In particular, we discuss the design, fabrication and functionalization of 2D biomaterials used for diverse biomedical applications based on the up-to-date progress. Furthermore, the interactions between 2D biomaterials and biological systems on the spatial–temporal scale are highlighted, which will deepen the understanding of the underlying action mechanism of 2D biomaterials aiding their design with improved functionalities. Finally, taking the bench-to-bedside as a focus, we conclude this review by proposing the current crucial issues/challenges and presenting the future development directions to advance the clinical translation of these emerging 2D biomaterials. [ABSTRACT FROM AUTHOR]

Biomimetic scaffolds loaded with drugs can be applied in bone tissue engineering. In this study, a series of three-dimensional polylactic acid/hydroxyapatite/graphene oxide (PLA/HA/GO) drug-loaded biomimetic composite scaffolds with different concentrations of aspirin (ASA; 0–50 wt%) was successfully prepared using the phase separation technique. ASA addition increased the scaffold pore size without destroying the biomimetic structure. The hydrophilicity of a PLA/HA/GO/ASA drug-loaded biomimetic composite scaffold is linked to the component and structure of the prepared scaffold. The porosity can reach >85% in all samples. A test to assess the apatite-formation ability confirmed that the prepared composite scaffold had good bioactivity and could induce the formation of spherical hydroxyapatites. The haemolysis rate, platelet adhesion and in vitro cell proliferation experiments showed that the prepared scaffold had good haemocompatibility and cytocompatibility. However, ASA addition demonstrated an inhibitory effect on MC3T3-E1 cells. The prepared PLA/HA/GO/ASA drug-loaded biomimetic composite scaffold revealed good sustained drug-release performance. Hence, different concentrations of ASA can be loaded onto the scaffold on the basis of therapy requirements. [ABSTRACT FROM AUTHOR]

Recently, nanomaterials have been widely utilized in tissue engineering applications due to their unique properties such as the high surface to volume ratio and diversity of morphology and structure. However, most methods used for the fabrication of nanomaterials are rather complicated and costly. Among different nanomaterials, anodic aluminum oxide (AAO) is a great example of nanoporous structures that can easily be engineered by changing the electrolyte type, anodizing potential, current density, temperature, acid concentration and anodizing time. Nanoporous anodic alumina has often been used for mammalian cell culture, biofunctionalization, drug delivery, and biosensing by coating its surface with biocompatible materials. Despite its wide application in tissue engineering, thorough in vivo and in vitro studies of AAO are still required to enhance its biocompatibility and thereby pave the way for its application in tissue replacements. Recognizing this gap, this review article aims to highlight the biomedical potentials of AAO for applications in tissue replacements along with the mechanism of porous structure formation and pore characteristics in terms of fabrication parameters. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disorder in which progressive articular cartilage loss occurs alongside pathological changes in subchondral bone and other joint tissues. The pathophysiological role of bone in OA has been a point of interest for many years and has resurfaced again in recent years as a potential target for new treatments. Articular cartilage and subchondral bone together form the osteochondral unit. Its homeostasis and integrity are reliant on biochemical crosstalk and biomechanical interplay between the two. Subchondral bone, with its relatively greater stiffness and strength, provides mechanical support to the overlying cartilage and absorbs much of the mechanical force transmitted through the joint. Mechanical instability in osteoarthritic joints is thought to be a significant risk-factor in joint disease, due to the mechano-sensitive nature of many of its native tissues. Although the progression of joint disease remains incompletely understood, significant changes in subchondral bone remodelling, structure, composition, and mechanical properties have been documented in animal and human studies of OA. The purpose of this review is to explore and discuss these bony changes associated with disease and, in particular, contextualise the basic science and clinical literature on the role of subchondral bone in OA. [ABSTRACT FROM AUTHOR]

Purpose: Ultrasound is a well-established technology in medical science, though many of the conventional measurement systems (hydrophones and radiation force balances [RFBs]) often lack accuracy and tend to be expensive. This is a significant problem where sensors must be considered to be "disposable" because they inevitably come into contact with biological fluids and expense increases dramatically in cases where a large number of sensors in array form are required. This is inevitably the case where ultrasound is to be used for the in vitro growth stimulation of a large plurality of biological samples in tissue engineering. Traditionally only a single excitation frequency is used (typically 1.5 MHz), but future research demands a larger choice of wavelengths for which a single broadband measurement transducer is desirable. Furthermore, because of implementation conditions there can also be large discrepancies between measurements. The purpose of this paper deals with a very cost-effective alternative to expensive RFBs and hydrophones. Design/methodology/approach: Utilization of cost-effective piezoelectric elements as broadband sensors. Findings: Very effective results with equivalent (if not better) accuracy than expensive alternatives. Originality/value: This paper concentrates on how very cost-effective piezoelectric ultrasound transducers can be implemented as sensors for ultrasound power measurements with accuracy as good, if not better than those achievable using radiation force balances or hydrophones. [ABSTRACT FROM AUTHOR]

Hemoderivative materials are used to treat different diseases. These derivatives include platelet‐rich plasma, serum, platelet gel, and platelet lysate (PL). Among them, PL contains more growth factors than the others and its production is inexpensive and easy. PL is one of the proper sources of platelet release factors. It is used in cells growth and proliferation and is a good alternative to fetal bovine serum. In recent years, the clinical use of PL has gained more appeal by scientists. PL is a solution saturated by growth factors, proteins, cytokines, and chemokines and is administered to treat different diseases such as wound healing, bone regeneration, alopecia, oral mucositis, radicular pain, osteoarthritis, and ocular diseases. In addition, it can be used in cell culture for cell therapy and tissue transplantation purposes. Platelet‐derived growth factor, fibroblast growth factor, insulin‐like growth factor, transforming growth factor β, and vascular endothelial growth factor are key PL growth factors playing a major role in cell proliferation, wound healing, and angiogenesis. In this paper, we scrutinized recent advances in using PL and PL‐derived growth factors to treat diseases and in regenerative medicine, and the ability to replace PL with other hemoderivative materials. [ABSTRACT FROM AUTHOR]

Diverse scaffold materials created from a variety of biomaterials via a plethora of production methods have been applied to redevelop varied tissues and body organs. Irrespective of the tissue type, a number of factors such as biodegradability, biocompatibility, mechanical properties, scaffold architecture and manufacturing technology are important when designing or determining the suitability of a scaffold for usage in tissue engineering. The plant-based natural polymers, being derived from green and sustainable sources, meet the requirements for such novel biomaterials with desirable properties for tissue engineering that require minimal chemical processing for industrial applications. The significant advantage of plant scaffolds is the apparent ease with which they can be made and manipulated; they are quite pliable and can be easily cut, fashioned, rolled or stacked to form a range of different sizes and shapes. They are also renewable, easy to mass produce and are relatively inexpensive. This review describes the use of plants and plant-based polymers and highlights the collective roles of such biomaterials in the assembly of greener and natural-based scaffolds for tissue engineering. [ABSTRACT FROM AUTHOR]

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Hydroxyapatite (HA), especially in the form of HA nanoparticles (HANPs), has excellent bioactivity, biodegradability, and osteoconductivity and therefore has been widely used as a template or additives for drug delivery in clinical applications, such as dentistry and orthopedic repair. Due to the atomically anisotropic distribution on the preferred growth of HA crystals, especially the nanoscale rod-/whisker-like morphology, HA can generally be a good candidate for carrying a variety of substances. HA is biocompatible and suitable for medical applications, but most drugs carried by HANPs have an initial burst release. In the adsorption mechanism of HA as a carrier, specific surface area, pore size, and porosity are important factors that mainly affect the adsorption and release amounts. At present, many studies have developed HA as a drug carrier with targeted effect, porous structure, and high porosity. This review mainly discusses the influence of HA structures as a carrier on the adsorption and release of active molecules. It then focuses on the benefits and effects of different types of polymer-HA composites to re-examine the proteins/drugs carry and release behavior and related potential clinical applications. This literature survey can be divided into three main parts: 1. interaction and adsorption mechanism of HA and drugs; 2. advantages and application fields of HA/organic composites; 3. loading and drug release behavior of multifunctional HA composites in different environments. This work also presents the latest development and future prospects of HA as a drug carrier. [ABSTRACT FROM AUTHOR]