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Background Bone regeneration involves various complex biological processes. Many experiments have been performed using biomaterials in vivo and in vitro to promote and understand bone regeneration. Among the many biomaterials, calcium phosphates which exist in the natural bone have been conducted a number of studies because of its bone regenerative property. It can be directly contributed to bone regeneration process or assist in the use of other biomaterials. Therefore, it is widely used in many applications and has been continuously studied. Mainbody Calcium phosphate has been widely used in bone regeneration applications because it shows osteoconductive and in some cases osteoinductive features. The release of calcium and phosphorus ions regulates the activation of osteoblasts and osteoclasts to facilitate bone regeneration. The control of surface properties and porosity of calcium phosphate affects cell/protein adhesion and growth and regulates bone mineral formation. Properties affecting bioactivity vary depending on the types of calcium phosphates such as HAP, TCP and can be utilized in various applications because of differences in ion release, solubility, stability, and mechanical strength. In order to make use of these properties, different calcium phosphates have been used together or mixed with other materials to complement their disadvantages and to highlight their advantages. Calcium phosphate has been utilized to improve bone regeneration in ways such as increasing osteoconductivity for bone ingrowth, enhancing osteoinductivity for bone mineralization with ion release control, and encapsulating drugs or growth factors. Conclusion Calcium phosphate has been used for bone regeneration in various forms such as coating, cement and scaffold based on its unique bioactive properties and bone regeneration effectiveness. Additionally, several studies have been actively carried out to improve the efficacy of calcium phosphate in combination with various healing agents. By summarizing the properties of calcium phosphate and its research direction, we hope that calcium phosphate can contribute to the clinical treatment approach for bone defect and disease.

Background Autogenous bone graft is the gold standard bone graft material. However, due to limitations of supply and morbidity associated with autograft harvest, various bone substitutes have been considered. This article aims to review the properties of the bone graft and various bone substitutes currently available in orthopedic surgery. Main body Synthetic bone substitutes consist of hydroxyapatite, tricalcium phosphate, calcium sulfate, or a combination of these minerals. Synthetic porous substitutes share several advantages over allografts, including unlimited supply, easy sterilization, and storage. However, they also have some disadvantages, such as brittle properties, variable rates of resorption, and poor performance in some clinical conditions. Recently, attention has been drawn to osteoinductive materials, such as demineralized bone matrix and bone morphogenetic proteins. Conclusion Despite tremendous efforts toward developing autograft alternatives, a single ideal bone graft substitute has not been developed. The surgeon should understand the properties of each bone graft substitute to facilitate appropriate selection in each specific clinical situation.

Background Titanium (Ti) has been utilized as hard tissue replacement owing to its superior mechanical and bioinert property, however, lack in tissue compatibility and biofunctionality has limited its clinical use. Reduced graphene oxide (rGO) is one of the graphene derivatives that possess extraordinary biofunctionality and are known to induce osseointegration in vitro and in vivo. In this study, rGO was uniformly coated by meniscus-dragging deposition (MDD) technique to fabricate rGO-Ti substrate for orthopedic and dental implant application. Methods The physicochemical characteristics of rGO-coated Ti (rGO-Ti) substrates were evaluated by atomic force microscopy, water contact angle, and Raman spectroscopy. Furthermore, human mesenchymal stem cells (hMSCs) were cultured on the rGO-Ti substrate, and then their cellular behaviors such as growth and osteogenic differentiation were determined by a cell counting kit-8 assay, alkaline phosphatase (ALP) activity assay, and alizarin red S staining. Results rGO was coated uniformly on Ti substrates by MDD process, which allowed a decrease in the surface roughness and contact angle of Ti substrates. While rGO-Ti substrates significantly increased cell proliferation after 7 days of incubation, they significantly promoted ALP activity and matrix mineralization, which are early and late differentiation markers, respectively. Conclusion It is suggested that rGO-Ti substrates can be effectively utilized as dental and orthopedic bone substitutes since these graphene derivatives have potent effects on stimulating the osteogenic differentiation of hMSCs and showed superior bioactivity and osteogenic potential.

Bone substitutes are being increasingly used in surgery as over two millions bone grafting procedures are performed worldwide per year. Autografts still represent the gold standard for bone substitution, though the morbidity and the inherent limited availability are the main limitations. Allografts, i.e. banked bone, are osteoconductive and weakly osteoinductive, though there are still concerns about the residual infective risks, costs and donor availability issues. As an alternative, xenograft substitutes are cheap, but their use provided contrasting results, so far. Ceramic-based synthetic bone substitutes are alternatively based on hydroxyapatite (HA) and tricalcium phosphates, and are widely used in the clinical practice. Indeed, despite being completely resorbable and weaker than cortical bone, they have exhaustively proved to be effective. Biomimetic HAs are the evolution of traditional HA and contains ions (carbonates, Si, Sr, Fl, Mg) that mimic natural HA (biomimetic HA). Injectable cements represent another evolution, enabling mininvasive techniques. Bone morphogenetic proteins (namely BMP2 and 7) are the only bone inducing growth factors approved for human use in spine surgery and for the treatment of tibial nonunion. Demineralized bone matrix and platelet rich plasma did not prove to be effective and their use as bone substitutes remains controversial. Experimental cell-based approaches are considered the best suitable emerging strategies in several regenerative medicine application, including bone regeneration. In some cases, cells have been used as bioactive vehicles delivering osteoinductive genes locally to achieve bone regeneration. In particular, mesenchymal stem cells have been widely exploited for this purpose, being multipotent cells capable of efficient osteogenic potential. Here we intend to review and update the alternative available techniques used for bone fusion, along with some hints on the advancements achieved through the experimental research in this field.

Polyetheretherketone (PEEK) is a polyaromatic semi-crystalline thermoplastic polymer with mechanical properties favorable for bio-medical applications. Polyetheretherketone forms: PEEK-LT1, PEEK-LT2, and PEEK-LT3 have already been applied in different surgical fields: spine surgery, orthopedic surgery, maxillo-facial surgery etc. Synthesis of PEEK composites broadens the physicochemical and mechanical properties of PEEK materials. To improve their osteoinductive and antimicrobial capabilities, different types of functionalization of PEEK surfaces and changes in PEEK structure were proposed. PEEK based materials are becoming an important group of biomaterials used for bone and cartilage replacement as well as in a large number of diverse medical fields. The current paper describes the structural changes and the surface functionalization of PEEK materials and their most common biomedical applications. The possibility to use these materials in 3D printing process could increase the scientific interest and their future development as well.

Background In dental or orthopedic surgery, bone substitutes are inserted with implants to promote osteogenesis and enhance osseointegration. The purpose of this research was to evaluate the efficacy of rhBMP-2 (recombinant human bone morphogenetic protein-2) loaded hydrogel composite for bone formation around dental implant in minipig mandible bone defect models. Methods We made bone defects with a diameter of 4 mm in minipig mandibles and inserted implants of the same size, to mimic the cases of inserting the screws in the bone defect or poor-quality bone. The rhBMP-2 (300 μg) loaded hydrogel composite (0.5 cc) inserted in the bone defect with the implant in the rhBMP-2 group. After 4 weeks, the mandibles were harvested to evaluate the new bone mass around implants using plain radiographs, micro-CT, and histology. Results The micro-CT analysis result showed that the quantity of new bone generation around the implant in the rhBMP-2 group was greater than that in the other groups. Comparing the ratios of bone to implant area in three groups by histology, the amount of newly formed bone in the rhBMP-2 group was the most. Conclusion The rhBMP-2 loaded hydrogel composite promotes osteogenesis around dental implant in minipig mandible bone defect, and enhance osseointegration between the dental implant and host bone.

Zinc is a micronutrient of key importance for human health. An increasing number of studies indicate that zinc plays a significant role in bone tissue’s normal development and maintaining homeostasis. Zinc is not only a component of bone tissue but is also involved in the synthesis of the collagen matrix, mineralization, and bone turnover. It has been demonstrated that zinc can stimulate runt-related transcription factor 2 (Runx2) and promote the differentiation of osteoblasts. On the other hand, zinc has been found to inhibit osteoclast-like cell formation and to decrease bone resorption by stimulating osteoclasts’ apoptosis. Moreover, zinc regulates the RANKL/RANK/OPG pathway, thereby facilitating bone remodeling. To date, not all mechanisms of Zn activity on bone tissue are well understood and documented. The review aimed to present the current state of research on the role of zinc in bone tissue, its beneficial properties, and its effects on bone regeneration. Since calcium phosphates as bone substitute materials are increasingly enriched in zinc ions, the paper included an overview of research on the potential role of such materials in bone filling and regeneration.

Nowadays, bone diseases and defects as a result of trauma, cancers, infections and degenerative and inflammatory conditions are increasing. Consequently, bone repair and replacement have been developed with improvement of orthopedic technologies and biomaterials of superior properties. This review paper is intended to sum up and discuss the most relevant studies performed in the field of bone biology and bone regeneration approaches. Therefore, the bone tissue regeneration was investigated by synthetic substitutes, scaffolds incorporating active molecules, nanomedicine, cell-based products, biomimetic fibrous and nonfibrous substitutes, biomaterial-based three-dimensional (3D) cell-printing substitutes, bioactive porous polymer/inorganic composites, magnetic field and nano-scaffolds with stem cells and bone–biomaterials interface studies.

Abstract Nowadays, biomaterials have evolved from the inert supports or functional substitutes to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of ‘biomaterials’, and a typical new insight is the concept of tissue induction biomaterials. The term ‘regenerative biomaterials’ and thus the contents of this article are relevant to yet beyond tissue induction biomaterials. This review summarizes the recent progress of medical materials including metals, ceramics, hydrogels, other polymers and bio-derived materials. As the application aspects are concerned, this article introduces regenerative biomaterials for bone and cartilage regeneration, cardiovascular repair, 3D bioprinting, wound healing and medical cosmetology. Cell-biomaterial interactions are highlighted. Since the global pandemic of coronavirus disease 2019, the review particularly mentions biomaterials for public health emergency. In the last section, perspectives are suggested: (i) creation of new materials is the source of innovation; (ii) modification of existing materials is an effective strategy for performance improvement; (iii) biomaterial degradation and tissue regeneration are required to be harmonious with each other; (iv) host responses can significantly influence the clinical outcomes; (v) the long-term outcomes should be paid more attention to; (vi) the noninvasive approaches for monitoring in vivo dynamic evolution are required to be developed; (vii) public health emergencies call for more research and development of biomaterials; and (viii) clinical translation needs to be pushed forward in a full-chain way. In the future, more new insights are expected to be shed into the brilliant field—regenerative biomaterials. Graphical Abstract

Traumatic, tumoral, and infectious bone defects are common in clinics, and create a big burden on patient’s families and society. Calcium phosphate (CaP)-based biomaterials have superior properties and have been widely used for bone defect repair, due to their similarities to the inorganic components of human bones. The biological performance of CaPs, as a determining factor for their applications, are dependent on their physicochemical properties. Hydroxyapatite (HAP) as the most thermally stable crystalline phase of CaP is mostly used in the form of ceramics or composites scaffolds with polymers. Nanostructured CaPs with large surface areas are suitable for drug/gene delivery systems. Additionally, CaP scaffolds with hierarchical nano-/microstructures have demonstrated excellent ability in promoting bone regeneration. This review focuses on the relationships and interactions between the physicochemical/biological properties of CaP biomaterials and their species, sizes, and morphologies in bone regeneration, including synthesis strategies, structure control, biological behavior, and the mechanisms of CaP in promoting osteogenesis. This review will be helpful for scientists and engineers to further understand CaP-based biomaterials (CaPs), and be useful in developing new high-performance biomaterials for bone repair.