MBG/BSA Bone Grafts Immunomodulate Bone Regeneration by Releasing Bioactive Ions in Inflammatory Bone Defects.

Since the diseases that cause bone defects are mostly inflammatory diseases, the current bone grafts are unable to effectively regulate osteoimmune activity, leading to the impaired osteogenesis and unfavorable bone regeneration. In this study, inspired by bone composition, biomimetic mesoporous bioactive glass nanoparticle (MBG)/bovine serum albumin (BSA) bone grafts are designed for inflammatory bone defects. Systematically, MBG/BSA bone grafts are evaluated for characterization, bioactivity, anti-inflammatory, antioxidant activity, and osteogenic activity. MBG/BSA bone grafts are proved to be biocompatible and can release bioactive ions including calcium and silicon in a sustained manner. Furthermore, MBG/BSA reprograms the macrophage phenotype toward anti-inflammation that is beneficial for bone regeneration. The antioxidative activity is also validated under inflammation and the mechanism may be via the interleukin-4 (IL-4)/Signal transducer and activator of transcription 6 (STAT6) pathway. The osteogenic differentiation and mineralization are also facilitated due to the improved immunoregulation of MBG/BSA. Overall, this work suggests that the MBG/BSA bone grafts with improved immunomodulatory properties are an ideal material for inflammatory bone regeneration application.

An Up-to-Date Review of Materials Science Advances in Bone Grafting for Oral and Maxillofacial Pathology.

Bone grafting in oral and maxillofacial surgery has evolved significantly due to developments in materials science, offering innovative alternatives for the repair of bone defects. A few grafts are currently used in clinical settings, including autografts, xenografts, and allografts. However, despite their benefits, they have some challenges, such as limited availability, the possibility of disease transmission, and lack of personalization for the defect. Synthetic bone grafts have gained attention since they have the potential to overcome these limitations. Moreover, new technologies like nanotechnology, 3D printing, and 3D bioprinting have allowed the incorporation of molecules or substances within grafts to aid in bone repair. The addition of different moieties, such as growth factors, stem cells, and nanomaterials, has been reported to help mimic the natural bone healing process more closely, promoting faster and more complete regeneration. In this regard, this review explores the currently available bone grafts, the possibility of incorporating substances and molecules into their composition to accelerate and improve bone regeneration, and advanced graft manufacturing techniques. Furthermore, the presented current clinical applications and success stories for novel bone grafts emphasize the future potential of synthetic grafts and biomaterial innovations in improving patient outcomes in oral and maxillofacial surgery.

Unleashing innovation: 3D-printed biomaterials in bone tissue engineering for repairing femur and tibial defects in animal models - a systematic review and meta-analysis.

Introduction: 3D-printed scaffolds have emerged as an alternative for addressing the current limitations encountered in bone reconstruction. This study aimed to systematically review the feasibility of using 3D bio-printed scaffolds as a material for bone grafting in animal models, focusing on femoral and tibial defects. The primary objective of this study was to evaluate the efficacy, safety, and overall impact of these scaffolds on bone regeneration. Methods: Electronic databases were searched using specific search terms from January 2013 to October 2023, and 37 relevant studies were finally included and reviewed. We documented the type of scaffold generated using the 3D printed techniques, detailing its characterization and rheological properties including porosity, compressive strength, shrinkage, elastic modulus, and other relevant factors. Before incorporating them into the meta-analysis, an additional inclusion criterion was applied where the regenerated bone area (BA), bone volume (BV), bone volume per total volume (BV/TV), trabecular thickness (Tb. Th.), trabecular number (Tb. N.), and trabecular separation (Tb. S.) were collected and analyzed statistically. Results: 3D bio-printed ceramic-based composite scaffolds exhibited the highest capacity for bone tissue regeneration (BTR) regarding BV/TV of femoral and tibial defects of animal models. The ideal structure of the printed scaffolds displayed optimal results with a total porosity >50% with a pore size ranging between 300- and 400 µM. Moreover, integrating additional features and engineered macro-channels within these scaffolds notably enhanced BTR capacity, especially observed at extended time points. Discussion: In conclusion, 3D-printed composite scaffolds have shown promise as an alternative for addressing bone defects.

Piezoelectric Heterojunctions as Bacteria-Killing Bone-Regenerative Implants.

Heterojunctions are widely used in energy conversion, environmental remediation, and photodetection, but have not been fully explored in regenerative medicine. In particular, piezoelectric heterojunctions have never been examined in tissue regeneration. Here the development of piezoelectric heterojunctions is shown to promote bone regeneration while eradicating pathogenic bacteria through light-cellular force-electric coupling. Specifically, an array of heterojunctions (TiO2/Bi2WO6), made of piezoelectric nanocrystals (Bi2WO6) decorating TiO2 nanowires, is fabricated as a biocompatible implant. Upon exposure to near-infrared light, the piezoelectric heterojunctions generate reactive oxygen species and heat to kill bacteria through photodynamic and photothermal therapy, respectively. Meanwhile, the mechanical forces of the stem cells grown on the implant trigger the heterojunctions to produce electric fields that further promote osteogenesis to achieve osteointegration. The heterojunctions effectively suppress postoperative recurrent infections while promoting osseointegration through the local electric fields induced by cells. Therefore, the piezoelectric heterojunctions represent a promising antibacterial tissue-regenerative implant.

The Masquelet technique triggers the formation of a network involving LncRNA, circRNA, miRNA, and mRNA during bone repair.

BACKGROUND: The ceRNA network, which is competitive endogenous RNA, uncovers a fresh mechanism of RNA interaction and holds significant importance in diverse biological processes. The aim of this study is to investigate the molecular process of induced membrane (IM) formation in bone defects using the Masquelet's induced membrane technique (MIMT), in order to offer novel insights and a theoretical foundation for enhancing the treatment of bone defects with MIMT. METHODS: In this work, we identified differentially expressed mRNAs (DEGs), lncRNAs (DELs), circRNAs (DECs), and miRNAs (DEMs). To explore the primary functions of the shared DEGs, we utilized Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, predictions were made for lncRNA-miRNA and miRNA-mRNA interactions, and the Cytoscape software was utilized to construct the regulatory network for ceRNA. RESULTS: By integrating GO and KEGG enrichment analysis, a total of 385 differentially expressed genes (DEGs) were discovered in the samples from the MIMT-treated group. Additionally, after re-annotating the probes and intersecting two sets of differently expressed miRNAs, 1304 differentially expressed lncRNAs (DELs) and 23 differentially expressed circRNAs (DECs) were identified. Furthermore, 13 differentially expressed miRNAs (DEMs) were obtained. Moreover, utilizing the anticipated objectives of DEMs, we acquired 1203 pairs of lncRNA-miRNA-mRNA interactors (comprising 24 lncRNAs, 10 miRNAs, and 115 mRNAs) and 250 pairs of circRNA-miRNA-mRNA interactions (comprising 7 circRNAs, 9 miRNAs, and 115 mRNAs). CEBPA, DGAT2, CDKN1A, PLIN2, and CIDEC were identified as the five hub proteins in the PPI network. LncRNA/circRNA-hsa-miR-671-5p could potentially regulate the primary central protein, CEBPA. CONCLUSIONS: In this study, we described the potential regulatory mechanism of the MIMT in treating bone defects. We proposed a new lncRNA-miRNA-mRNA ceRNA network that could help further explore the molecular mechanisms of bone repair.

Local application of melatonin associated or not to xenogeneic material, in critical defects of rat calvaria.

Melatonin (MLT) is a hormone that can stimulate bone formation and inhibit bone resorption, among other functions. Aim: To evaluate the effect on new bone formation of MLT applied locally to critical defects created in the calvaria of rats, compared to the effect of Bio-Oss® xenogeneic bone substitute (BO), by analyzing histomorphometry, microtomography and gene expression. Materials and Method: Two critical defects (5.0 mm in diameter) were created in the calvaria of 36 adults male Wistar rats. The rats were divided randomly into two groups: a test group, in which one of the defects was filled with MLT, and the other with MLT with Bio-Oss® (MLTBO), and a control group, in which one of the defects was filled only with the clot (C), and the other with BO. The rats were euthanized 30 days after surgery. Samples of the calvaria containing the critical defects were collected for analysis by histomorphometry, microtomography, and the expression of the genes for type I collagen (COL-I), osteopontin (OPN) and bone morphogenetic protein 2 (BMP-2). Results: A qualitative improvement was observed in bone healing when MLT was used, though there was no statistical difference in the quantification of newly formed bone (p>0.05). Micro-CT showed that bone volume was significantly smaller in absence of BO (p=0.006). Bone trabeculae thickness (p=0.590) and number (p=0.150) were not significantly affected by MLT. Regarding the expression of the genes COL-I, OPN and BMP-2, no significant differences were observed between the MLT, BO and MLTBO groups. Conclusion: Topical application of MLT resulted in a qualitative improvement in bone healing, although it did not affect bone formation quantitatively. In the absence of BO, less bone volume and less bone trabecular thickness were observed.

A melatonina (MLT) é um hormônio sintetizado e secretado pela glândula pineal, e que, dentre outras atividades e funções, tem capacidade de estimular a formação e inibir a reabsorção óssea. Objetivo: avaliar o efeito da aplicação local do hormônio MLT na neoformação óssea, em defeitos críticos produzidos na calvária de ratos, por meio de análise histomorfométrica, microtomográfica e de biologia molecular, comparando-a com um substituto ósseo de origem xenogênica (Bio-Oss®). Materiais e Método: foram utilizados 36 ratos Wistar machos adultos, nos quais foram produzidos dois defeitos críticos de 5,0 mm de diâmetro cada, que receberam diferentes tratamentos alocados de forma randomizada: no grupo controle, os animais tiveram um dos defeitos preenchidos apenas com coágulo sanguíneo (C) e o outro com substituto ósseo xenógeno (Bio-Oss®, BO); no grupo teste, um dos defeitos foi preenchido apenas com MLT e, o outro, recebeu a associação da MLT ao material sintético xenógeno (MLTBO). Todos os animais foram eutanasiados após 30 dias do pós-operatório. As amostras das calotas contendo os defeitos críticos foram coletadas para análises histomorfométricas, microtomográficas e da expressão gênica de colágeno do tipo I (COL-I), osteopontina (OPN) e proteína óssea morfogenética 2 (BMP-2), por meio de PCR em tempo real. Resultados: Após análise dos dados pode-se observar que não houve diferença estatística na quantificação de neoformação óssea (p>0.05), porém, melhora qualitativa foi observada na cicatrização, quando a MLT foi utilizada. Quanto aos par®metros microtomográficos, foi observado que com ou sem MLT, o volume ósseo foi significativamente menor na ausência de BO. A espessura (p = 0,590) e número (p = 0,150) de trabéculas não foram significativamente afetados pelo uso da MLT. Quanto à expressão gênica de COL-I, OPMN e BMP-2, não foram observadas diferenças significativas entre os grupos MLT, BO e MLTBO. Conclusão: conclui-se que a aplicação tópica de MLT, associada ou não ao BO não afetou quantitativamente a neoformação óssea, porém resultou em uma melhora qualitativa na cicatrização. Adicionalmente, na ausência de BO foi observada menor volume ósseo e menor espessura das trabéculas.

Vancomycin-Loaded in situ Gelled Hydrogel as an Antibacterial System for Enhancing Repair of Infected Bone Defects.

Purpose: During treatment of infected bone defects, control of infection is necessary for effective bone repair, and hence controlled topical application of antibiotics is required in clinical practice. In this study, a biodegradable drug delivery system with in situ gelation at the site of infection was prepared by integrating vancomycin into a polyethylene glycol/oxidized dextran (PEG/ODEX) hydrogel matrix. Methods: In this work, PEG/ODEX hydrogels were prepared by Schiff base reaction, and vancomycin was loaded into them to construct a drug delivery system with controllable release and degradability. We first examined the microstructure, degradation time and drug release of the hydrogels. Then we verified the biocompatibility and in vitro ability of the release system. Finally, we used a rat infected bone defect model for further experiments. Results: The results showed that this antibacterial system could be completely biodegradable in vivo for 56 days, and its degradation products did not cause specific inflammatory response. The cumulative release of vancomycin from the antibacterial system was 58.3% ± 3.8% at 14 days and 78.4% ± 3.2% at 35 days. The concentration of vancomycin in the surrounding environment was about 1.2 mg/mL, which can effectively remove bacteria. Further studies in vivo showed that the antibacterial system cleared the infection and accelerated repair of infected bone defects in the femur of rats. There was no infection in rats after 8 weeks of treatment. The 3D image analysis of the experimental group showed that the bone volume fraction (BV/TV) was 1.39-fold higher (p < 0.001), the trabecular number (Tb.N) was 1.31-fold higher (p < 0.05), and the trabecular separation (Tb.Sp) was 0.58-fold higher than those of the control group (p < 0.01). Conclusion: In summary, this study clearly demonstrates that a clinical strategy based on biological materials can provide an innovative and effective approach to treatment of infected bone defects.

Vancomycin-encapsulated hydrogel loaded microarc-oxidized 3D-printed porous Ti6Al4V implant for infected bone defects: Reconstruction, anti-infection, and osseointegration.

Infected bone defect is a formidable clinical challenge. Conventional approaches to prevention and treatment for infected bone defects are unsatisfactory. The key elements of the treatment are bone defect reconstruction, anti-infection, and osteogenesis. Conventional treatment methods remain unsatisfactory owing to the absence of composite integrating materials with anti-infective, and osteogenic activities as well as proper mechanical strength at the same time. In this study, we fabricated a vancomycin-encapsulated hydrogel with bacteria-responsive release properties combined with a shaved porous (submicron-micron) three-dimensional-printed Ti6Al4V implant. The implant surface, modified with submicron-sized pores through microarc oxidation (MAO), showed enhanced osteogenic activity and integrated well with the hydrogel drug release system, enabling sustained vancomycin release. In vitro experiments underscored the commendable antibacterial ability, biosafety, and osteoinductive potential. Effective antibacterial and osteogenic abilities of the implant were further demonstrated in vivo in infected rabbit bone defects. These results showed that the vancomycin-encapsulated hydrogel-loaded microarc-oxidized 3D-printed porous Ti6Al4V can repair the infected bone defects with satisfactory anti-infection and osseointegration effects.

A Case of Varus Collapse and Bone Defects in Revision Total Knee Arthroplasty, after 12 Years of Primary Total Knee Replacement: Surgical Challenge and Bailout.

Introduction: The failure of total knee arthroplasties (TKA) due to aseptic implant loosening is now the most common cause of long-term failure. Patients with varus alignment of the tibial or femoral component with additional bone collapse are a specific subset. It is unclear, however, whether implant fixation fails first or if bone collapse occurs first. Case Report: A 70-year-old lady with 12-year post-primary total knee arthroplasty presented with limping gate with radiological evidence of medial femoral bone collapse and implant loosening. After appropriate pre-operative planning, intraoperatively, after the removal of loose femoral implant which had additional bone loss and careful removal of a well-fixed tibial implant and to prevent collapse due to bone loss, Stryker LCCK implant with long stems on both sides was used. Additional screws on the medial femoral end, along with cement to fill the gap. After 5 years of follow-up, the patient is doing well with a painless full range of movement of the knee joint. Conclusion: Preoperatively one should always evaluate for bone loss and infection and compare with the other side. In case of aseptic collapse of bones, the use of thicker stems is a good way as these act as weight-sharing implants, and proper cementation during revision TKA is essential.

Near-Infrared Carbon Dots With Antibacterial and Osteogenic Activities for Sonodynamic Therapy of Infected Bone Defects.

Repairing infected bone defects is hindered by the presence of stubborn bacterial infections and inadequate osteogenic activity. The incorporation of harmful antibiotics not only fosters the emergence of multidrug-resistant bacteria, but also diminishes the osteogenic properties of scaffold materials. In addition, it is essential to continuously monitor the degradation kinetics of scaffold materials at bone defect sites, yet the majority of bone repair materials lack imaging capability. To address these issues, this study reports for the first time the development of a single nanomaterial with triple functionality: efficient sonodynamic antibacterial activity, accelerated bone defect repair capability, and NIR imaging ability for visualized therapy of infected bone defects. Through rationally regulating the surface functional groups, the obtained multifunctional NIR carbon dots (NIR-CD) exhibit p-n junction-enhanced sonodynamic activity, narrow bandgap-facilitated NIR imaging capability, and negative charge-augmented osteogenic activity. The validation of NIR-CDs antibacterial and osteogenic activities in vivo is conducted by constructing 3D injectable hydrogels encapsulated by NIR-CDs (NIR-CD/GelMA). The implantation of multifunctional NIR-CD/GelMA hydrogel scaffolds in a model of MRSA-infected craniotomy defects results in almost complete restoration of the infected bone defects after 60 days. These findings will provide traceable, renewable, repairable and antibacterial candidate biomaterials for bone tissue engineering.

Smart Implantable Hydrogel for Large Segmental Bone Regeneration.

Large segmental bone defects often lead to nonunion and dysfunction, posing a significant challenge for clinicians. Inspired by the intrinsic bone defect repair logic of "vascularization and then osteogenesis", this study originally reports a smart implantable hydrogel (PDS-DC) with high mechanical properties, controllable scaffold degradation, and timing drug release that can proactively match different bone healing cycles to efficiently promote bone regeneration. The main scaffold of PDS-DC consists of polyacrylamide, polydopamine, and silk fibroin, which endows it with superior interfacial adhesion, structural toughness, and mechanical stiffness. In particular, the adjustment of scaffold cross-linking agent mixing ratio can effectively regulate the in vivo degradation rate of PDS-DC and intelligently satisfy the requirements of different bone defect healing cycles. Ultimately, PDS hydrogel loaded with free desferrioxamine (DFO) and CaCO3 mineralized ZIF-90 loaded bone morphogenetic protein-2 (BMP-2) to stimulate efficient angiogenesis and osteogenesis. Notably, DFO is released rapidly by free diffusion, whereas BMP-2 is released slowly by pH-dependent layer-by-layer disintegration, resulting in a significant difference in release time, thus matching the intrinsic logic of bone defect repair. In vivo and in vitro results confirm that PDS-DC can effectively realize high-quality bone generation and intelligently regulate to adapt to different demands of bone defects.

Enhanced bone formation of rat mandibular bone defects with collagen membranes loaded on bone morphogenetic protein-9.

Background/purpose: Bone morphogenetic protein-9 (BMP-9) has demonstrated multiple advantages in promoting osteogenesis. Our previous findings have indicated that the use of an absorbable collagen membrane (ACM) as a carrier for growth factors is effective in stimulating bone regeneration. The objective of this study was to assess the synergistic impact of BMP-9 incorporated into ACM (ACM/BMP-9) on bone formation within rat mandibular bone defects. Materials and methods: Circular bone defects of critical size were surgically induced on both sides of the rat mandibular bone, with subsequent random allocation into distinct groups: control, ACM alone, and ACM loaded with low (0.5 µg) or high (2.0 µg) concentrations of BMP-9. We conducted real-time in vivo micro-computerized tomography scans at the baseline and at 2, 4, and 6 weeks, and measured the volume of newly formed bone (NFB), bone mineral density (BMD) of NFB, and the closure percentage of the NFB area. Histological and histomorphometric analyses were performed at 6 weeks. Results: Real-time assessment revealed notably higher levels of bone volume, BMD, and closure percentage in the NFB area for the groups treated with ACM/BMP-9 compared to the control and ACM groups. Within the high concentration of BMP-9 group, the volume and BMD of NFB exhibited a significant increase at 6 weeks compared to baseline. Histological examination confirmed the existence of osteoblasts, osteocytes, and blood vessels within the NFB. Conclusion: Considering the limitations of this research, the real-time evaluation finding indicates that ACM/BMP-9 effectively promotes bone formation in critical-size mandibular defects in rats.

Combined use of PRPP, diode laser and piezosurgery device improves reparative osteogenesis previously to dental implants placement.

OBJECTIVE: Current study evaluated whether use of the platelet-rich powder (PRPP), piezosurgery device and diode laser after removal of jawbones cysts and benign bone formations and extraction of impacted tooth could enhance bone regeneration before dental implantation. METHODS: A study was conducted among 200 patients with post-surgical cavities (not exceeding 1.5 cm upon cystectomy, benign bone tumor removal and impacted tooth extraction) who underwent plasma powder, autograft, allograft, xenograft or beta-tricalcium phosphate augmentation procedures. RESULTS: PRPP implantation in combination with irradiation of bone cavity by diode laser led to the formation of 15.40 % ± 2.1 of new bone. The activity of reparative osteogenesis on the bone surface was BB = 6.71 ± 1.3, which is 3 and 3.5 times higher than the mean value in comparison group after augmentation of xenograft and beta-tricalcium phosphate. The value of bone tissue resorption for main group patients was less pronounced (Ra.Oc = 25.20 % ± 2.1). The ratio between pro- and anti-inflammatory cytokines in the main group after 1, 7 and 30 days since surgical procedure was lower than the ratio of the corresponding cytokines in the comparison groups. CONCLUSION: The examination of computed tomograms, histological and morphometric analysis of bone tissue after trepanobiopsy, cytological analysis of swabs and enzyme immunoassay to determine local immunity indicated that the proposed method of treatment with the use of PRPP, the piezosurgery device and the diode laser has a positive effect: it helped to optimize reparative osteogenesis after filling post-surgical cavities and restore bone volume.

A Treatment Algorithm for Free Vascularized Bone Reconstruction in Rare Large Osseous Defects Involving the Wrist.

Large bone defects of the distal radius and/or carpus following tumor resection, trauma, or infection are extremely rare. There are few case reports and series in the literature on the reconstruction approaches required in such cases. Therefore, large studies cannot be used to guide the therapeutic decisions of reconstructive plastic and hand surgeons. The objective of this study is to propose a treatment algorithm to predict the functional outcome and quality of life for the different techniques of free vascularized bone reconstruction in the interval between the distal radius, the carpus, and/or the proximal metacarpal. The algorithm was developed based on our own case studies and the few treatment approaches described in the literature. It can be applied to rare cases of massive bone defects in the wrist. The flowchart enables surgeons to develop an individualized reconstruction concept for various intervals of bone defects in the area of the distal radius and proximal metacarpal bones. Ultimately, the treatment algorithm aims to maximize future quality of life (QoL) and function of the distal upper extremity in rare cases of massive wrist-bone defects.

Incorporation of small extracellular vesicles in PEG/HA-Bio-Oss hydrogel composite scaffold for bone regeneration.

Stem cell derived small extracellular vesicles (sEVs) have emerged as promising nanomaterials for the repair of bone defects. However, low retention of sEVs affects their therapeutic effects. Clinically used natural substitute inorganic bovine bone mineral (Bio-Oss) bone powder lacks high compactibility and efficient osteo-inductivity that limit its clinical application in repairing large bone defects. In this study, a poly ethylene glycol/hyaluronic acid (PEG/HA) hydrogel was used to stabilize Bio-Oss and incorporate rat bone marrow stem cell-derived sEVs (rBMSCs-sEVs) to engineer a PEG/HA-Bio-Oss (PEG/HA-Bio) composite scaffold. Encapsulation and sustained release of sEVs in hydrogel scaffold can enhance the retention of sEVs in targeted area, achieving long-lasting repair effect. Meanwhile, synergistic administration of sEVs and Bio-Oss in cranial defect can improve therapeutic effects. The PEG/HA-Bio composite scaffold showed good mechanical properties and biocompatibility, supporting the growth of rBMSCs. Furthermore, sEVs enhancedin vitrocell proliferation and osteogenic differentiation of rBMSCs. Implantation of sEVs/PEG/HA-Bio in rat cranial defect model promotedin vivobone regeneration, suggesting the great potential of sEVs/PEG/HA-Bio composite scaffold for bone repair and regeneration. Overall, this work provides a strategy of combining hydrogel composite scaffold systems and stem cell-derived sEVs for the application of tissue engineering repair.

Ti3C2Tx@PLGA/Icaritin microspheres-modified PLGA/ß-TCP scaffolds modulate Icaritin release to enhance bone regeneration through near-infrared response.

Porous poly (lactic-co-glycolic acid)/ß-tricalcium phosphate/Icaritin (PLGA/ß-TCP/ICT, PTI) scaffold is a tissue engineering scaffold based on PLGA/ß-TCP (PT) containing Icaritin, the main active ingredient of the Chinese medicine Epimedium. Due to its excellent mechanical properties and osteogenic effect, PTI scaffold has the potential to promote bone defect repair. However, the release of ICT from the scaffolds is difficult to control. In this study, we constructed Ti3C2Tx@PLGA/ICT microspheres (TIM) and evaluated their characterization as well as ICT release under near-infrared (NIR) irradiation. We utilized TIM to modify the PT scaffold and performed biological experiments. First, we cultured rat bone marrow mesenchymal stem cells on the scaffold to assess biocompatibility and osteogenic potential under on-demand NIR irradiation. Subsequently, to evaluate the osteogenic properties of TIM-modified scaffoldin vivo, the scaffold was implanted into a femoral condyle defect model. TIM have excellent drug-loading capacity and encapsulation efficiency for ICT, and the incorporation of Ti3C2Txendows TIM with photothermal conversion capability. Under 0.90 W cm-2NIR irradiation, the temperature of TIM maintained at 42.0 ± 0.5 °C and the release of ICT was accelerated. Furthermore, while retaining its original properties, the TIM-modified scaffold was biocompatible and could promote cell proliferation, osteogenic differentiation, and biomineralizationin vitro, as well as the osteogenesis and osseointegrationin vivo, and its effect was further enhanced through the modulation of ICT release under NIR irradiation. In summary, TIM-modified scaffold has the potential to be applied in bone defects repairing.

Targeting Bacteria-Induced Ferroptosis of Bone Marrow Mesenchymal Stem Cells to Promote the Repair of Infected Bone Defects.

The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.

Role of Sticky Bone in the Management of Various Alveolar Bone Defects: A Systematic Review.

AIM: This systematic review aimed to evaluate the effectiveness of sticky bone in managing various alveolar bone defects, examining both its benefits and drawbacks. MATERIALS AND METHODS: The review adhered to PRISMA guidelines and employed a thorough search strategy using major databases, medical subject headings (MeSH) keywords, and Boolean operators. As a result, the systematic review identified 12 studies focusing on the efficacy of sticky bone in treating alveolar bone defects. Inclusion criteria consisted of randomized controlled trials and case series reporting on the outcomes of sticky bone use for bone defect treatment. Two examiners meticulously performed screening, data extraction, and bias assessment, with the risk of bias evaluated using the Cochrane tool. RESULT: The findings indicated significant improvements in bone quality, width, height, and volume, with enhanced predictability in socket preservation and implant placement. Sticky bone was particularly effective in ridge augmentation, guided bone regeneration, and filling periodontal defects, often outperforming alternatives like concentrated growth factors (CGFs) and autologous fibrin glue (AFG). It simplified procedures and reduced resorption during healing, underscoring its value as a versatile adjunct in bone reconstruction surgery. CONCLUSION: Sticky bone demonstrated exceptional results in various oral surgeries, effectively addressing issues such as furcation defects, bone loss, and ridge augmentation, with significant clinical and radiographic improvements. Further research is needed to explore its full potential and refine protocols for broader oral surgery and periodontics applications.

Osteoinductive potential of graphene and graphene oxide for bone tissue engineering: a comparative study.

BACKGROUND: Bone defects, especially critical-size bone defects, and their repair pose a treatment challenge. Osteoinductive scaffolds have gained importance given their potential in bone tissue engineering applications. METHODS: Polycaprolactone (PCL) scaffolds are used for their morphological, physical, cell-compatible and osteoinductive properties. The PCL scaffolds were prepared by electrospinning, and the surface was modified by layer-by-layer deposition using either graphene or graphene oxide. RESULTS: Graphene oxide-coated PCL (PCL-GO) scaffolds showed a trend for enhanced physical properties such as fibre diameter, wettability and mechanical properties, yield strength, and tensile strength, compared to graphene-modified PCL scaffolds (PCL-GP). However, the surface roughness of PCL-GP scaffolds showed a higher trend than PCL-GO scaffolds. In vitro studies showed that both scaffolds were cell-compatible. Graphene oxide on PCL scaffold showed a trend for enhanced osteogenic differentiation of human umbilical cord Wharton's jelly-derived Mesenchymal Stem Cells without any differentiation media than graphene on PCL scaffolds after 21 days. CONCLUSION: Graphene oxide showed a trend for higher mineralisation, but this trend is not statistically significant. Therefore, graphene and graphene oxide have the potential for bone regeneration and tissue engineering applications. Future in vivo studies and clinical trials are warranted to justify their ultimate clinical use.