Research progress on applications of bioactive glass matrix composites in bone repair

Damage mechanisms in bioactive glass matrix composites under uniaxial compression.

To review the research and application progress of bioactive glass in bone repair. The recently published literature concerning bioactive glass in bone repair was reviewed and summarized. Bioactive glass can classified different types, such as bioactive glass particulate, bioactive glass scaffold, bioactive glass coating, injectable bioactive glass cement, and bioactive glass delivery system. Bioactive glass has been well studied in the field of bone repair due to its excellent biological properties. Also, the remarkable progress has been made in various aspects. Bioactive glass is a reliable material of bone repair and will play an even more important role in the future.

ABSTRACTBones can fulfill functions in movement, attachment, and protection of internal organs. Bone diseases caused by ageing, trauma, infection, and other reasons may seriously affect the daily life of patients. Magnesium ions are closely associated with the maintenance of bone health. Integrating magnesium ions into delivery systems and hydrogels can improve their application, thus directly acting on the osteoblast cell lineage and influencing the proliferation and differentiation of relevant cells. The slow release of magnesium ions allows for their effects on the target site for a long time, reducing the clearance of magnesium ions in the body, which significantly contributes to bone repair. Magnesium-based bioalloy scaffolds have received widespread attention for their favourable biocompatibility, degradability, and bone-forming properties and play an important role in bone regeneration and repair. This article presents a review on the role and mechanism of magnesium-containing materials in bone repair and regeneration. By discussing the current challenges and future directions for magnesium-containing biomaterials, new insights are provided into the development of these materials in the field of orthopaedics. In conclusion, magnesium-containing biomaterials have great application value in orthopaedics.

For a long time, how to repair the bone defects caused by bone trauma, bone tuberculosis and other bone diseases, is one of the difficult problems faced by surgeons. In the process of bone formation and repair, the periosteum, as an important "place" for blood supply and bone formation and regeneration, its importance is self-evident. However, the number of healthy periosteum cannot meet the repair of large bone defects, and tissue engineering periosteum emerged at the historic moment. At the same time, the selection of biocompatible and prepared biomaterials to promote bone healing and bone repair has gradually attracted great attention from clinicians and researchers. Based on the material, design and preparation methods of tissue engineering periosteum, this paper reviews the research progress and application prospect of tissue engineering periosteum materials, which provides valuable reference for further profound research, and also provides basic ideas and methods.

To review the methods of improving the mechanical properties of hydrogels and the research progress in bone tissue engineering. The recent domestic and foreign literature on hydrogels in bone tissue engineering was reviewed, and the methods of improving the mechanical properties of hydrogels and the effect of bone repair in vivo and in vitro were summarized. Hydrogels are widely used in bone tissue engineering, but their mechanical properties are poor. Improving the mechanical properties of hydrogels can enhance bone repair. The methods of improving the mechanical properties of hydrogels include the construction of dual network structures, inorganic nanoparticle composites, introduction of conductive materials, and fiber network reinforcement. These methods can improve the mechanical properties of hydrogels to various degrees while also demonstrating a significant bone repair impact. The mechanical properties of hydrogels can be effectively improved by modifying the system, components, and fiber structure, and bone repair can be effectively promoted.

To review the research progress of natural biomaterial polyhydroxyalkanoate (PHA) in orthopedics. The literature concerning PHA devices for bone defects, bone repair, and bone neoplasms, respectively, in recent years was extensively consulted. The three aspects of the advantages of PHA in bone repair, the preparation of PHA medical devices for bone repair and their application in orthopedics were discussed. Due to excellent biodegradability, biocompatibility, and potential osteoinduction, PHA is a kind of good bone repair material. In addition to the traditional PHA medical implants, the use of electrostatic spinning and three-dimensional printing can be designed to various functional PHA medical devices, in order to meet the orthopedic clinical demands, including the bone regeneration, minimally invasive bone tissue repair by injection, antibacterial bone repair, auxiliary establishment of three-dimensional bone tumor model, directed osteogenic differentiation of stem cells, etc. At present, PHA is a hotspot of biomaterials for translational medicine in orthopedics. Although they have not completely applied in the clinic, the advantages of repair in bone defects have been gradually reflected in tissue engineering, showing an application prospect in orthopedics.

Researchers have investigated several therapeutic approaches to treat non-union fractures. Among these, bioactive glasses and glass ceramics have been widely used as grafts. This class of biomaterial has the ability to integrate with living bone. Nevertheless, bioglass and bioactive materials have been used mainly as powder and blocks, compromising the filling of irregular bone defects. Considering this matter, our research group has developed a new bioactive glass composition that can originate malleable fibers, which can offer a more suitable material to be used as bone graft substitutes. Thus, the aim of this study was to assess the morphological structure (via scanning electron microscope) of these fibers upon incubation in phosphate buffered saline (PBS) after 1, 7 and 14 days and, also, evaluate the in vivo tissue response to the new biomaterial using implantation in rat tibial defects. The histopathological, immunohistochemistry and biomechanical analyzes after 15, 30 and 60 days of implantation were performed to investigate the effects of the material on bone repair. The PBS incubation indicated that the fibers of the glassy scaffold degraded over time. The histological analysis revealed a progressive degradation of the material with increasing implantation time and also its substitution by granulation tissue and woven bone. Histomorphometry showed a higher amount of newly formed bone area in the control group (CG) compared to the biomaterial group (BG) 15 days post-surgery. After 30 and 60 days, CG and BG showed a similar amount of newly formed bone. The novel biomaterial enhanced the expression of RUNX-2 and RANK-L, and also improved the mechanical properties of the tibial callus at day 15 after surgery. These results indicated a promising use of the new biomaterial for bone engineering. However, further long-term studies should be carried out to provide additional information concerning the material degradation in the later stages and the bone regeneration induced by the fibrous material.

Bones normally function to provide both mechanical and locomotion supports in the body. They are highly specialized connective tissues that are characterized by mineralized extracellular components, which provide both rigidity and strength to bones. Stem cells hold great potentials for both the repair and regeneration of different tissue types, including bone tissues. The future use of stem cell therapy is promising for developing regenerative medicine approaches to treat disorders and diseases in a wide range of tissues such as cartilages and bones. Data have been accumulated recently on the application of different stem cell types in bone repair, regeneration, and disorders. In this article, we briefly describe the bone structure and review research progress and recently accumulated data on stem cell differentiation into osteoblasts as well as discuss the contributions of stem cell types to bone and cartilage repair, regeneration, and disease.

To summarize the clinical application and research status of bioactive glass (BAG) in bone repair. The recently published literature concerning BAG in bone repair at home and abroad was reviewed and summarized. BAG has been widely used in clinical bone repair with a favorable effectiveness. In the experimental aspect, to meet different clinical application needs, BAG has been prepared in different forms, such as particles, prosthetic coating, drug and biological factor delivery system, bone cement, and scaffold. And the significant progress has been made. BAG has been well studied in the field of bone repair due to its excellent bone repair performance, and it is expected to become a new generation of bone repair material.

Functional reconstruction of bone defects represents a clinical challenge in the regenerative medicine field, which targets tissue repair following traumatic injuries and disease-related bone deficiencies. In this regard, the optimal biomaterial should be safe, biocompatible and tailored in order to promote the activation of host progenitor cells towards bone repair. Bioactive glasses might be suitable biomaterials due to their composition being able to induce the host healing response and, eventually, anti-bacterial properties. In this study we investigated whether and how an innovative bioactive glass composition, called BGMS10, may affect cell adhesion, morphology, proliferation, immunomodulation and osteogenic differentiation of human dental pulp stem cells (hDPSCs). When cultured on BGMS10, hDPSCs maintained their proliferation rate and typical fibroblast-like morphology, showing the expression of stemness markers STRO-1 and c-Kit. Moreover, the expression of FasL, a key molecule in mediating immunomodulation effects of hDPSCs, was maintained. BGMS10 also proved to trigger osteogenic commitment of hDPSCs, as confirmed by the activation of bone-related transcription factors RUNX2 and Osx and the ongoing deposition of extracellular matrix supported by the expression of OPN and OCN. Our findings suggest that BGMS10 not only maintains the typical biological and immunomodulatory properties of hDPSCs but also favors the osteogenic commitment.

Ceramics used for the repair and reconstruction of diseased or damaged parts of the musculo‐skeletal system, termed bioceramics, may be bioinert (e.g., alumina and zirconia), resorbable (e.g., tricalcium phosphate), bioactive (e.g., hydroxyapatite, bioactive glasses, and glass‐ceramics), or porous for tissue ingrowth (e.g., hydroxyapatite‐coated metals). Applications include replacements for hips, knees, teeth, tendons, and ligaments and repair for periodontal disease, maxillofacial reconstruction, augmentation and stabilization of the jaw bone, spinal fusion, and bone repair after tumor surgery. Pyrolytic carbon coatings are thromboresistant and are used for prosthetic heart valves. The mechanisms of tissue bonding to bioactive ceramics have resulted in the molecular design of bioceramics for interfacial bonding with hard and soft tissue. Bioactive composites are being developed with high toughness and elastic modulus that match with bone. Therapeutic treatment of cancer has been achieved by localized delivery of radioactive isotopes via glass beads. Clinical success of bioceramics has led to a remarkable advance in the quality of life for millions of people.

Purpose: The treatment of bone repair has always been a focus of research. In recent years, new metals have been increasingly used for bone repair, and many related studies have been published. However, until now, there has been no bibliometric analysis of these publications. This study uses bibliometrics to evaluate the current research status in this field to predict future research hotspots and development trends and promote the development and progress of this field.Methods: Global publications on metal materials and bone repair from January 2012 to December 2021 were extracted from the Web of Science database. Microsoft Excel 2016, GraphPad Prism 8, VOSviewer, and CiteSpace were employed to perform the bibliometric study and data visualization.Results: China contributed the most publications and had the most citations and H-index, especially in the last five years. The journal Materials Science and Engineering C-Materials for Biological Applications published the most papers. The Chinese Academy of Sciences had the most publications among all institutions. The top 10 articles by citations mainly focused on porous polymer scaffolds and the metals zinc and magnesium.Conclusion: We predict that the total number of global publications will grow in the future according to the relative research interest. Importantly, the current research focus has shifted from metal materials to osteogenic mechanisms. Porous scaffolds, degradation rate, tissue engineering, angiogenesis, and stem cells could be research hotspots in the future.

Pulsed electromagnetic field (PEMF) stimulation is a prospective non-invasive and safe physical therapy strategy for accelerating bone repair. PEMFs can activate signalling pathways, modulate ion channels, and regulate the expression of bone-related genes to enhance osteoblast activity and promote the regeneration of neural and vascular tissues, thereby accelerating bone formation during bone repair. Although their mechanisms of action remain unclear, recent studies provide ample evidence of the effects of PEMF on bone repair. In this review, we present the progress of research exploring the effects of PEMF on bone repair and systematically elucidate the mechanisms involved in PEMF-induced bone repair. Additionally, the potential clinical significance of PEMF therapy in fracture healing is underscored. Thus, this review seeks to provide a sufficient theoretical basis for the application of PEMFs in bone repair.

To review the application and research progress of in-situ tissue engineering technology in bone and cartilage repair. The original articles about in-situ tissue engineering technology in bone and cartilage repair were extensively reviewed and analyzed. In-situ tissue engineering have been shown to be effective in repairing bone defects and cartilage defects, but biological mechanisms are inadequate. At present, most of researches are mainly focused on animal experiments, and the effect of clinical repair need to be further studied. In-situ tissue engineering technology has wide application prospects in bone and cartilage tissue engineering. However, further study on the mechanism of related cytokines need to be conducted.

Purpose. This study aimed to explore if initiation of biomimetic apatite nucleation can be used to enhance osteoblast response to biodegradable tissue regeneration composite membranes. Materials and Methods. Bioactive thermoplastic composites consisting of poly(ε-caprolactone/DL-lactide) and bioactive glass (BAG) were prepared at different stages of biomimetic calcium phosphate deposition by immersion in simulated body fluid (SBF). The modulation of the BAG dissolution and the osteogenic response of rat mesenchymal stem cells (MSCs) were analyzed. Results. SBF treatment resulted in a gradual calcium phosphate deposition on the composites and decreased BAG reactivity in the subsequent cell cultures. Untreated composites and composites covered by thick calcium phosphate layer (14 days in SBF) expedited MSC mineralization in comparison to neat polymers without BAG, whereas other osteogenic markers—alkaline phosphatase activity, bone sialoprotein, and osteocalcin expression—were initially decreased. In contrast, surfaces with only small calcium phosphate aggregates (five days in SBF) had similar early response than neat polymers but still demonstrated enhanced mineralization. Conclusion. A short biomimetic treatment enhances osteoblast response to bioactive composite membranes.