OBJECTIVE: Two of the most exciting new technologies are biotechnology and nanotechnology. The science of nanostructures, or nanotechnology, is concerned with the development, testing, and use of structures and molecules with nanoscale dimensions ranging from 1 to 100 nm. The development of materials and tools with high specificity that interact directly at the subcellular level is what makes nanotechnology valuable in the medical sciences. At the cellular or tissue level, this might be converted into focused clinical applications with the greatest possible therapeutic benefits and the fewest possible side effects. The purpose of the present study was to review the literature and explore the applicability of the nanostructured materials in the process of the regeneration of the soft and hard tissues of the oral cavity.
METHODS: An electronic search of articles was conducted in several databases, such as PubMed, Embase, and Web of Science, to conduct this study, and the 183 articles that were discovered were chosen and examined, and only 22 articles met the inclusion criteria in this review.
RESULTS: The findings of this study demonstrate that using nanoparticles can improve the mechanical properties, biocompatibility, and osteoinductivity of biomaterials.
CONCLUSIONS: Most recently, breakthroughs in tissue engineering and nanotechnology have led to significant advancements in the design and production of bone graft substitutes and hold tremendous promise for the treatment of bone abnormalities. The creation of intelligent nanostructured materials is essential for various applications and therapies, as it allows for the precise and long-term delivery of medication, which yields better results.

Bone regeneration poses a significant challenge in the field of tissue engineering, prompting ongoing research to explore innovative strategies for effective bone healing. The integration of stem cells and nanomaterial scaffolds has emerged as a promising approach, offering the potential to enhance regenerative outcomes. This study focuses on the application of a stem cell-laden nanomaterial scaffold designed for bone regeneration in rabbits. The in vivo study was conducted on thirty-six healthy skeletally mature New Zealand white rabbits that were randomly allocated into six groups. Group A was considered the control, wherein a 15 mm critical-sized defect was created and left as such without any treatment. In group B, this defect was filled with a polycaprolactone-hydroxyapatite (PCL + HAP) scaffold, whereas in group C, a PCL + HAP-carboxylated multiwalled carbon nanotube (PCL + HAP + MWCNT-COOH) scaffold was used. In group D, a PCL + HAP + MWCNT-COOH scaffold was used with local injection of bone morphogenetic protein-2 (BMP-2) on postoperative days 30, 45, and 60. The rabbit bone marrow-derived mesenchymal stem cells (rBMSCs) were seeded onto the PCL + HAP + MWCNT-COOH scaffold by the centrifugal method. In group E, an rBMSC-seeded PCL + HAP + MWCNT-COOH scaffold was used along with the local injection of rBMSC on postoperative days 7, 14, and 21. For group F, in addition to the treatment given to group E, BMP-2 was administered locally on postoperative days 30, 45, and 60. Gross observations, radiological observation, scanning electron microscopic assessment, and histological evaluation study showed that group F displayed the best healing properties, followed by group E, group D, group C, and B. Group A showed no healing with ends blunting minimal fibrous tissue. Incorporating growth factor BMP-2 in tissue-engineered rBMSC-loaded nanocomposite PCL + HAP + MWCNT-COOH construct can augment the osteoinductive and osteoconductive properties, thereby enhancing the healing in a critical-sized bone defect. This novel stem cell composite could prove worthy in the treatment of non-union and delayed union fractures in the near future.

Nowadays, there is an increasing prevalence of bone diseases and defects caused by trauma, cancers, infections, and degenerative and inflammatory conditions. The restoration of bone tissue lost due to trauma, fractures, or surgical removal resulting from locally invasive pathologies requires bone regeneration. As an alternative to conventional treatments, sustainable materials based on natural products, such as honeybee-derived products (honey, propolis, royal jelly, bee pollen, beeswax, and bee venom), could be considered. Honeybee-derived products, particularly honey, have long been recognized for their healing properties. There are a mixture of phytochemicals that offer bone protection through their antimicrobial, antioxidant, and anti-inflammatory properties. This review aims to summarize the current evidence regarding the effects of honeybee-derived products on bone regeneration. In conclusion, honey, propolis, royal jelly, beeswax, and bee venom can potentially serve as natural products for promoting bone health.

Fracture healing is a very complex physiological process involving multiple events at different temporal and spatial scales, such as cell migration and tissue differentiation, in which mechanical stimuli and biochemical factors assume key roles. With the continuous improvement of computer technology in recent years, computer models have provided excellent solutions for studying the complex process of bone healing. These models not only provide profound insights into the mechanisms of fracture healing, but also have important implications for clinical treatment strategies. In this review, we first provide an overview of research in the field of computational models of fracture healing based on CiteSpace software, followed by a summary of recent advances, and a discussion of the limitations of these models and future directions for improvement. Finally, we provide a systematic summary of the application of computational models of fracture healing in three areas: bone tissue engineering, fixator optimization and clinical treatment strategies. The application of computational models of bone healing in clinical treatment is immature, but an inevitable trend, and as these models become more refined, their role in guiding clinical treatment will become more prominent.

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Periosteum is a highly vascularized membrane lining the surface of bones. It plays essential roles in bone repair following injury and reconstruction following invasive surgeries. To broaden the use of periosteum, including for augmenting in vitro bone engineering and/or in vivo bone repair, we have developed an ex vivo perfusion bioreactor system to maintain the cellular viability and metabolism of surgically resected periosteal flaps. Each specimen was placed in a 3D printed bioreactor connected to a peristaltic pump designed for the optimal flow rates of tissue perfusate. Nutrients and oxygen were perfused via the periosteal arteries to mimic physiological conditions. Biochemical assays and histological staining indicate component cell viability after perfusion for almost 4 weeks. Our work provides the proof-of-concept of ex vivo periosteum perfusion for long-term tissue preservation, paving the way for innovative bone engineering approaches that use autotransplanted periosteum to enhance in vivo bone repair.

Prevascularization is crucial for the survival of tissue-engineered bone and further bone repair/regeneration. Since epicatechin gallate (ECG), the most abundant flavanol in green tea, shows potential beneficial effects on endothelial cells and bone cells, we decided to investigate whether it promotes vascularization/angiogenesis and osteogenesis using a co-culture system containing human primary osteoblasts (POBs) and outgrowth endothelial cells (OECs). We found that treatment with ECG (1) significantly enhanced microvessel formation in co-culture of POB and OECs, (2) improved cell viability/proliferation and the angiogenic/osteogenic capacities of OEC/POBs, (3) significantly increased the levels of E-selectin, IL-6, TNF-α, IFN-γ, VEGF, and PDGF-BB in co-cultures of POB and OEC, and (4) upregulated HIF-1α, HIF-2α, NF-κB, iNOS, GLUT1, VEGF, and Ang1/2 but downregulated PHD1 in monocultures of OEC or POB. Our findings demonstrate that ECG promotes angiogenesis and osteogenesis (probably via HIF signaling) in co-cultures of OECs and POBs. ECG thus has potential applications in the promotion of angiogenesis/vascularization in many tissue constructs including those of bone.

Bone regeneration after injury or after surgical bone removal due to disease is a serious medical challenge. A variety of materials are being tested to replace a missing bone or tooth. Regeneration requires cells capable of proliferation and differentiation in bone tissue. Although there are many possible human cell types available for use as a model for each phase of this process, no cell type is ideal for each phase. Osteosarcoma cells are preferred for initial adhesion assays due to their easy cultivation and fast proliferation, but they are not suitable for subsequent differentiation testing due to their cancer origin and genetic differences from normal bone tissue. Mesenchymal stem cells are more suitable for biocompatibility testing, because they mimic natural conditions in healthy bone, but they proliferate more slowly, soon undergo senescence, and some subpopulations may exhibit weak osteodifferentiation. Primary human osteoblasts provide relevant results in evaluating the effect of biomaterials on cellular activity; however, their resources are limited for the same reasons, like for mesenchymal stem cells. This review article provides an overview of cell models for biocompatibility testing of materials used in bone tissue research.

Side effects caused by bone fractures and restrictions on bone regeneration impose an enormous economic burden on the health system of society. To overcome these limitations, tissue engineering and cell-based therapies have been proposed as alternatives to induce and promote bone healing. Still, bone regeneration disadvantages, such as limited and painful surgery, the risk of infection, nerve injury, bleeding, and function damage, have led investigators to find an alternative therapy. In some studies, bone stimulants have prompted scientists to design scaffolds with appropriate physical structure with the possibility of cell adhesion and proliferation, which plays an influential role in the regeneration and repair of bone tissue. PCL nanofiber is an absorbing candidate for the formulation of biocompatible scaffolds used in tissue engineering. To overcome these negative aspects, improve the properties of PCL nanofibers, and based on the biocompatibility and superior mechanical properties of POSS, Polyhedral Oligomeric Silsesquioxane-Polycaprolactone-Zeolite (POSS-PCL-Zeolite) nanocomposite electrospun nanofiber scaffolds were fabricated in the present study. Nanohybrids and nanofibers structures were characterized by FTIR, HNMR, XRD, SEM, EDX, and DSC techniques. We used cellular and molecular assays, including DCFH ROS detection system, gene expression (RUNX-2, Osteocalcin, Nrf2, BAX, VEGF gens), and apoptotic to demonstrate the biocompatibility and induce bone differentiation of formulated POSS-PCL-Zeolite scaffolds. The results showed the biodegradability of POSS-PCL-Zeolite Nano-scaffold and supported the nesting of mesenchymal stem cells (MSCs) and induced bone differentiation by POSS-PCL-Zeolite Nano-scaffold.

Engineering living bone tissue of defined shape on-demand has remained a challenge. 3D bioprinting (3DBP), a biofabrication process capable of yielding cell constructs of defined shape, when combined with developmental engineering can provide a possible path forward. Through the development of a bioink possessing appropriate rheological properties to carry a high cell load and concurrently yield physically stable structures, printing of stable, cell-laden, single-matrix constructs of anatomical shapes is realized without the need for fugitive or support phases. Using this bioink system, constructs of hypertrophic cartilage of predesigned geometry are engineered in vitro by printing human mesenchymal stromal cells at a high density to drive spontaneous condensation and implanted in nude mice to evoke endochondral ossification. The implanted constructs retain their prescribed shape over a 12-week period and undergo remodeling to yield ossicles of the designed shape with neovascularization. Microcomputed tomography, histological, and immunohistochemistry assessments confirm bone tissue characteristics and the presence of human cells. These results demonstrate the potential of 3DBP to fabricate complex bone tissue for clinical application.