Healing Of Bone Defects Research Articles

Supplemental Magnesium Gluconate Enhances Scaffold-Mediated New Bone Formation and Natural Bone Healing by Angiogenic- and Wnt Signal-Associated Osteogenic Activation.

Local implantation or supplementation of magnesium gluconate (MgG) is being investigated as an effective approach to bone repair. Although studies have highlighted the possible mechanisms in Mg ion-stimulated new bone formation, the role of MgG in healing bone defects and the signaling mechanisms are not yet completely understood. In this study, we explored how supplemental MgG has bone-specific beneficial effects by delivering MgG locally and orally in animal models. We fabricated MgG-incorporated (CMC-M) and -free chitosan (CMC) scaffolds with good microstructures and biocompatible properties. Implantation with CMC-M enhanced bone healing in rat model of mandible defects, compared with CMC, by activating Wnt signals and Wnt-related osteogenic and angiogenic molecules. Oral supplementation with MgG also stimulated bone healing in mouse model of femoral defects along with the increases in Wnt3a and angiogenic and osteogenic factors. Supplemental MgG did not alter nature bone accrual and bone marrow (BM) microenvironment in adult mouse model, but enhanced the functioning of BM stromal cells (BMSCs). Furthermore, MgG directly stimulated the induction of Wnt signaling-, angiogenesis-, and osteogenesis-related molecules in cultures of BMSCs, as well as triggered the migration of endothelial cells. These results suggest that supplemental MgG improves bone repair in a way that is synergistically enhanced by Wnt signal-associated angiogenic and osteogenic molecules. Overall, this study indicates that supplemental MgG might ameliorate oxidative damage in the BM, improve the functionality of BM stem cells, and maintain BM-microenvironmental homeostasis.

Revolutionizing bone defect healing: the power of mesenchymal stem cells as seeds

Bone defects can arise from trauma or pathological factors, resulting in compromised bone integrity and the loss or absence of bone tissue. As we are all aware, repairing bone defects is a core problem in bone tissue engineering. While minor bone defects can self-repair if the periosteum remains intact and normal osteogenesis occurs, significant defects or conditions such as congenital osteogenesis imperfecta present substantial challenges to self-healing. As research on mesenchymal stem cell (MSC) advances, new fields of application have emerged; however, their application in orthopedics remains one of the most established and clinically valuable directions. This review aims to provide a comprehensive overview of the research progress regarding MSCs in the treatment of diverse bone defects. MSCs, as multipotent stem cells, offer significant advantages due to their immunomodulatory properties and ability to undergo osteogenic differentiation. The review will encompass the characteristics of MSCs within the osteogenic microenvironment and summarize the research progress of MSCs in different types of bone defects, ranging from their fundamental characteristics and animal studies to clinical applications.

Serum biochemical evaluation of healing of critical-sized long bone defects in rats treated with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds

Critical-sized long bone defects are those that would not heal spontaneously despite surgical stabilisation. The use of bioceramic scaffold has shown promising results in the repair of bone defects. The present study was undertaken to evaluate the serum biochemical parameters of Wistar rats treated for critical-sized segmental bone loss using biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds. The study was conducted in eighty male Wistar rats aged between 8-12 weeks, weighing 200-250 g body weight with critical-sized segmental defects in the femur. A 6 mm segmental mid-diaphyseal femoral defect was created under general anaesthesia. The bone defect was bridged with bioceramic scaffolds and retained in position with microplate and screws. Serum biochemical parameters serum calcium, phosphorous, acid phosphatase and alkaline phosphatase were evaluated four weeks before surgery, immediately after surgery and 4th, 8th, 12th, and 16th week after surgery. The evaluation of both serum calcium and phosphorous were found to be reliable indicators of new bone formation and mineralisation, whereas the evaluation of both serum acid phosphatase and alkaline phosphatase were found to be reliable indicators of bone healing during the treatment of critical-sized long bone defects in rats using biphasic hydroxyapatite and β-tricalcium phosphate bioceramic scaffolds Keywords: Beta-tricalcium phosphate, bioceramic scaffold, hydroxyapatite, serum acid phosphatase, serum alkaline phosphatase, serum calcium, serum phosphorous

Biomechanical evaluation of healing of critical-sized long bone defects in rats treated with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds

Critical-sized bone defects are those that would not heal spontaneously despite surgical stabilisation. These defects are treated using autografts, allografts, xenografts and synthetic bone grafts. The present study was undertaken to evaluate the efficacy of biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds in treating critical-sized segmental bone loss in rats. The study was conducted in sixty male Wistar rats aged between 8-12 weeks, weighing 200-250 g body weight with critical-sized defects in the right femur. A six-mm segmental mid-diaphyseal femoral defect was created under general anaesthesia. The bone defect was bridged with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds and retained in position with microplate and screws. Fifteen rats were sacrificed as per the guidelines of CCSEA during the 4th, 8th, 12th and 16th week post-surgery. The treated bone and contralateral femur were harvested and subjected to a three-point bending test, torsion test and compression test to compare the regained strength of the repaired right femur with that of the intact contralateral left femur. From the present study, it was observed that the use of biphasic hydroxyapatite and β-tricalcium phosphate bioceramic scaffolds in the treatment of critical-sized long bone defects in rats resulted in biomechanical properties of the healed right femur greatly superior to the femur with untreated critical-sized diaphyseal defect by sixteenth week post-surgery and was only slightly inferior to the normal intact left femur. The results were suggestive of using biphasic hydroxyapatite and β-tricalcium phosphate bioceramics scaffolds as a safe and promising alternative for the treatment of critical-sized bone defects Keywords: Beta-tricalcium phosphate, bioceramic scaffold, compression test, hydroxyapatite, three-point bending test and torsion test

Investigation of the Effects of Ozon and Propolis on the Healing of Bone Defects: An Experimental Study

Background/aim: This study explores the effects of ozone and propolis on the healing of critically sized bone defects at both the histologic and molecular levels, and the locations and concentrations of osteopontin and osteonectin during healing; both proteins play roles during bone healing. Materials and methods: This study used 56 adult male Sprague-Dawley rats of an average weight of 350 g, divided into four groups of 14: a control group, a topical ozone group (O), a topical ozone + systemic propolis (O + PO) group, and a systemic propolis group (PO). Seven rats from each group were sacrificed at the end of week 4 and the other seven at the end of week 6. Tissues were subjected to histologic and immunohistochemical examinations in a fixative solution. The results were analyzed using the statistical software package SPSS 23 (Statistical Package for the Social Sciences—IBM). Results were considered significant at the 95% confidence level (P<0.05). Results: Graft sections were immunostained for osteonectin. Staining was low in the control group but moderate in the other three groups; the differences were significant. The three experimental groups did not differ significantly. Graft sections were also immunostained for osteonectin. At 4 weeks, staining was low in the control group but moderate in the other 3 groups. At 6 weeks, stronger staining was apparent in the 3 experimental groups. At both 4 and 6 weeks, the differences between the control and experimental groups were significantly different, but the differences among the experimental groups were not. Conclusion: The authors' results are compatible with the literature. Ozone and propolis, given separately or together, improved bone healing, increased bone formation, and reduced bone destruction. However, further research is required.

The Biomimetic Electrical Stimulation System Inducing Osteogenic Differentiations of BMSCs.

Electrical stimulation has been used clinically as an adjunct therapy to accelerate the healing of bone defects, and its mechanism requires further investigations. The complexity of the physiological microenvironment makes it challenging to study the effect of electrical signal on cells alone. Therefore, an artificial system mimicking cell microenvironment in vitro was developed to address this issue. In this work, a novel electrical stimulation system was constructed based on polypyrrole nanowires (ppyNWs) with a high aspect ratio. Synthesized ppyNWs formed a conductive network in the composited hydrogel which contained modified gelatin with methacrylate, providing a conductive cell culture matrix for bone marrow mesenchymal stem cells. The dual-network conductive hydrogel had improved mechanical, electrical, and hydrophilic properties. It was able to imitate the three-dimensional structure of the cell microenvironment and allowed adjustable electrical stimulations in the following system. This hydrogel was integrated with cell culture plates, platinum electrodes, copper wires, and external power sources to construct the artificial electrical stimulation system. The optimum voltage of the electrical stimulation system was determined to be 2 V, which exhibited remarkable biocompatibility. Moreover, this system had significant promotion in cell spreading, osteogenic makers, and bone-related gene expression of stem cells. RNA-seq analysis revealed that osteogenesis was correlated to Notch, BMP/Smad, and calcium signal pathways. It was proven that this biomimetic system could regulate the osteogenesis procedure, and it provided further information about how the electrical signal regulates osteogenic differentiations.

Magnesium Nanocomposite Hydrogel Reverses the Pathologies to Enhance Mandible Regeneration.

The healing of bone defects after debridement in medication-related osteonecrosis of the jaw (MRONJ) is a challenging medical condition with impaired angiogenesis, susceptible infection, and pro-inflammatory responses. Magnesium (Mg) nanocomposite hydrogel is developed to specifically tackle multiple factors involved in MRONJ. Mg-oxide nanoparticles tune the gelation kinetics in the reaction between N-hydroxysuccinimide-functionalized hyperbranched poly (ethylene glycol) and proteins. This reaction allows an enhanced mechanical property after instant solidification and, more importantly, also stable gelation in challenging environments such as wet and hemorrhagic conditions. The synthesized hydrogel guides mandible regeneration in MRONJ rats by triggering the formation of type H vessels, activating Osterix+ osteoprogenitor cells, and generating anti-inflammatory microenvironments. Additionally, this approach demonstrates its ability to suppress infection by inhibiting specific pathogens while strengthening stress tolerance in the affected alveolar bone. Furthermore, the enhanced osteogenic properties and feasibility of implantation of the hydrogel are validated in mandible defect and iliac crest defect created in minipigs, respectively. Collectively, this study offers an injectable and innovative bone substitute to enhance mandible defect healing by tackling multiple detrimental pathologies.

Photoactivated Hydrogel Therapeutic System with MXene-Based Nanoarchitectonics Potentiates Endogenous Bone Repair Through Reshaping the Osteo-Vascularization Network.

The repair and reconstruction of large-scale bone defects face enormous challenges because of the failure to reconstruct the osteo-vascularization network. Herein, a near-infrared (NIR) light-responsive hydrogel system is reported to achieve programmed tissue repair and regeneration through the synergetic effects of on-demand drug delivery and mild heat stimulation. The spatiotemporal hydrogel system (HG/MPa) composed of polydopamine-coated Ti3C2Tx MXene (MP) nanosheets decorated with acidic fibroblast growth factor (aFGF, a potent angiogenic drug) and hydroxypropyl chitosan/gelatin (HG) hydrogel is developed to orchestrate the reconstruction of the osteo-vascularization network and boost bone regeneration. Upon exposure to NIR light irradiation, the engineered HG/MPa hydrogel can achieve the initial complete release of aFGF to induce rapid angiogenesis and provide sufficient blood supply, maximizing its biofunction in the defect area. This integrated hydrogel system demonstrated good therapeutic efficacy in promoting cell adhesion, proliferation, migration, angiogenesis, and osteogenic differentiation through periodic NIR irradiation. In vivo, animal experiments further revealed that the spatiotemporalized hydrogel platform synergized with mild photothermal treatment significantly accelerated critical-sized bone defect healing by increasing the osteo-vascularization network density, recruiting endogenous stem cells, and facilitating the production of osteogenesis/angiogenesis-related factors. Overall, smart-responsive hydrogel couldenhance the reconstruction of the osteo-vascularization network in bone regeneration.

Hierarchical Integration of Curcumin-Loaded CaCO3 Nanoparticles and Black Phosphorus Nanosheets in Core/Shell Nanofiber for Cranial Defect Repair.

Reconstruction and healing of large craniofacial bone defects are major clinical challenges due to high risk of chronic inflammation and reduced cell mineralization levels. Herein, a core-shell nanofiber-based implant with significant pro-osteogenesis capability for treating skull defects is reported, which is hierarchically integrated with curcumin-loaded calcium carbonate nanoparticles (CaCO3@Cur NPs) in the outer layers and black phosphorus nanosheets (BPNSs) in the core compartments. The radical alignment of the integrated nanocomponents allows the sequential in situ release of the therapeutic agents in a controlled manner after implantation. Curcumin can repolarize M1 macrophages into M2 phenotypes for anti-inflammation purposes. Meanwhile, the released calcium and phosphate ions can promote the biomineralization of hydroxyapatite at the defect site and facilitate bone regeneration. Evaluations on cranial defect-bearing rat models demonstrated that the electrospun fibers in the present study substantially promoted restoration of the damaged skulls and inhibited inflammation in the wound bed. This strategy provides a new idea for the treatment of skull defects in the clinic.

The efficacy of Nano-crystalline hydroxyapatite combined with parathyroid hormone versus Nano-crystalline hydroxyapatite alone on healing of bone defect after cyst enucleation: a randomized clinical trial (RCT)

The efficacy of Nano-crystalline hydroxyapatite combined with parathyroid hormone versus Nano-crystalline hydroxyapatite alone on healing of bone defect after cyst enucleation: a randomized clinical trial (RCT)

Effects of vitamin K2 administration on guided bone regeneration in diabetic rats.

The present study aimed to investigate the histomorphometric and immunohistochemical impacts of vitamin K2 on guided bone regeneration (GBR) in calvarial critical-size defects (CSDs) in diabetic rats. A total of 30 rats were used in this study, comprising 12 non-diabetic (control) rats and 18 with streptozotocin-nicotinamide-induced experimental Diabetes mellitus (DM). In all rats, two calvarial CSDs were created: one defect was left empty (E), the other was treated with bovine-derived bone graft and collagen-based resorbable membrane (GM). Study groups were as follows: control rats administered saline (n = 6, C-E and C-GM groups) or vitamin K2 (n = 6, CK-E and CK-GM groups) and diabetic rats administered saline (n = 6, DM-E and DM-GM groups) or vitamin K2 (n = 6, DMK-E and DMK-GM groups). After 4 weeks of saline or vitamin K2 administration, the rats were euthanized. Bone defect healing and new bone formation were assessed histomorphometrically, and osteocalcin and osteopontin levels were examined immunohistochemically. Percentage of new bone formation was greater in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 3.86 (95% CI = 16.38-28.61), d = 1.86, (95% CI = 10.74-38.58), respectively, p < .05]. Bone defect healing scores were higher in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 2.69 (95% CI = -2.12 to -0.87), d = 3.28 (95% CI = 0.98-1.91), respectively, p < .05]. Osteocalcin expression levels were elevated in CK-GM vs. CK-E, in DMK-GM vs. DMK-E [d = 1.19 (95% CI = 0.08-1.41), d = 1.10 (95% CI = 0.02-1.22), respectively p < .05]. Vitamin K2 enhanced osteocalcin expression levels in DMK-E vs. DM-E [d = 2.78, (95% CI = 0.56-1.53), p < .05] and in DMK-GM vs. DM-GM [d = 2.43, (95% CI = 0.65-2.10), p < .05]. Osteopontin expression was enhanced in defects treated with GM vs. E defects [C-GM vs. C-E, d = 1.56 (95% CI = 0.38-2.01); CK-GM vs. CK-E, d = 1.91 (95% CI = 0.49-1.72); DM-GM vs. DM-E, d = 2.34 (95% CI = -1.12 to -0.50); DMK-GM vs. DMK-E, d = 2.00 (95% CI = 0.58-1.91), p < .05]. The research findings suggest that administering vitamin K2 in GBR for rats with DM favorably impacts bone healing in CSDs, presenting an adjunctive strategy for bone regeneration.

Nanocarrier-Assisted Delivery of Berberine Promotes Diabetic Alveolar Bone Regeneration by Scavenging ROS and Improving Mitochondrial Dysfunction.

Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an active plant alkaloid, exhibits multiple pharmacological effects including antioxidation, blood glucose- and blood lipid-lowering properties. However, it remains uncertain whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM), and its poor solubility and oral bioavailability also constrain its applications in bone regeneration. Thus, our study aimed to probe the effects of berberine on bone marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis on developing a suitable nano-delivery system for berberine and assessing its capability to repair diabetic alveolar bone defects. Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA) environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next, we explored the regulatory mechanism of autophagy flux in the positive effects of berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed tomography and histology analysis. Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane with excellent physicochemical properties and good biological safety had the potential to promote alveolar bone remodeling in T2DM rats. Our study shed new lights into the protective role of berberine on BMSCs under T2DM microenvironment. Furthermore, berberine-loaded composite electrospun membrane may serve as a promising approach for regenerating alveolar bone in diabetic patients.

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.

Injectable, oxygen-releasing, thermosensitive hydrogel promotes vascularized bone formation with prolonged oxygen delivery and improved osteoinductivity

The failure or delay in healing of critical bone defects is primarily due to early local anoxic conditions and reduced osteogenic activity. In this research, we integrated calcium peroxide (CPO) embedded polycaprolactone (PCL) microspheres and osteoinductive nanoparticles (Hydroxyapatite/Laponite) into a thermosensitive hydrogel (Pluronic F127), thereby formulating an injectable oxygen-releasing osteogenic thermosensitive hydrogel. Notably, the oxygen-releasing microspheres (ORMs) within the composite hydrogel provide stable oxygen release for up to 21 days, ensuring the survival, migration, and bioactivity of both mesenchymal stem cells and endothelial cells under anoxic conditions. Additionally, the composite hydrogel significantly augments the osteogenic potential of bone marrow mesenchymal stem cells by providing a biomimetic microenvironment with the incorporation of nano-hydroxyapatite/laponite. Ultimately, the injectable composite hydrogel successfully stimulated bone regeneration within a cranial defect in a rat model after 8 weeks, with enhanced vascularization and bone quality. The engineered hydrogel provides a minimally invasive approach to stimulate bone regeneration with a sustained oxygen supply and osteogenic microenvironment provision, underlining its potential for treating critical bone defects.

Increased bone mass but delayed mineralization: in vivo and in vitro study for zoledronate in bone regeneration

BackgroundBisphosphonates (BPs) are widely used to inhibit excessive osteoclast activity. However, the potential to compromise bone defect healing has limited their broader application. To better understand the influence of BPs on bone regeneration, we established a bone grafting model with Zoledronate administration, aiming to deepen the understanding of bone remodeling and mineralization processes.MethodsA bone grafting model was established in the distal femurs of male Sprague–Dawley rats. The experimental group received systemic administration of Zoledronate (ZOL, 0.2 mg/kg, administered twice). Histological analysis and immunohistochemistry (IHC) were employed to assess osteoblastic and macrophage activity, tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclastogenesis. Mineralization was assessed through Micro-CT analysis, Raman spectroscopy, and back-scatter scanning electron microscopy (BSE-SEM). Additionally, the in vitro effects of ZOL on osteoblast and osteoclast activity were investigated to further elucidate its impact on bone regeneration.ResultsIn vivo, the ZOL group showed increased bone mass, as observed in histological and radiological assessments. However, Micro-CT, Raman spectroscopy, and BSE-SEM detection revealed lower mineralization levels in ZOL group's regenerated bone. Acid-etched SEM analysis showed abnormal osteocyte characteristics in ZOL-group’s regenerated bone. Simultaneously, elevated osteopontin (OPN), F4/80 expression along with reduced TRAP expressing was found in the grafting region of ZOL group. In vitro, ZOL did not negatively impact osteogenetic activity (ALP, BMP4, OCN expression) at the tested concentrations (0.02–0.5 g/ml) but significantly impaired mineralization and inhibited osteoclast formation, even at the lowest concentration.ConclusionsThis study highlights a less recognized negative effect of ZOL on bone mineralization during bone regeneration. More research is needed to elucidate the underlying mechanism.

Regeneration of Critical Calvarial Bone Defects Using Bovine Xenograft, Magnesium-Enriched Bovine Xenograft and Autologous Dentin in Rats: Micro-CT, Gene Expression and Immunohistochemical Analysis.

The aim of this study was to evaluate the efficacy of autologous dentin (AD), bovine xenograft (BX) and magnesium-enriched bovine xenograft (BX + Mg) in the healing of critical cranial bone defects (CCBDs) in rats. Eighty male Wistar rats were divided into four groups: BX, BX + Mg, AD and the control group (no intervention). Eight mm CCBDs were created and treated with the respective biomaterials. Healing was assessed 7, 15, 21 and 30 days after surgery by micro-computed tomography (micro-CT), real-time polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Micro-CT analysis showed that AD had the highest bone volume and the least amount of residual biomaterial at day 30, indicating robust bone formation and efficient resorption. BX + Mg showed significant bone volume but had more residual biomaterial compared to AD. RT-PCR showed that the expression of osteocalcin (OC), the receptor activator of nuclear factor κB (RANK) and sclerostin (SOST), was highest in the AD group at day 21 and vascular endothelial growth factor (VEGF) at day 15, indicating increased osteogenesis and angiogenesis in the AD group. Immunohistochemical staining confirmed intense BMP-2/4 and SMAD-1/5/8 expression in the AD group, indicating osteoinductive properties. The favorable gene expression profile and biocompatibility of AD and BX + Mg make them promising candidates for clinical applications in bone tissue engineering. Further research is required to fully exploit their potential in regenerative surgery.

Hydrogel Microsphere-Encapsulated Bimetallic Nanozyme for Promoting Diabetic Bone Regeneration via Glucose Consumption and ROS Scavenging.

The healing of bone defects among diabetic patients presents a critical challenge due to the pathological microenvironment, characterized by hyperglycemia, excessive reactive oxygen species (ROS) production, and inflammation. Herein, multifunctional composite microspheres, termed GMAP are developed, using a microfluidic technique by incorporating Au@Pt nanoparticles (NPs) and GelMA hydrogel to modulate the diabetic microenvironment for promoting bone regeneration. The GMAP enables the sustained release of Au@Pt NPs, which function as bimetallic nanozymes with dual enzyme-like activities involving glucose oxidase and catalase. The synergistic effect allows for efficient glucose consumption and ROS elimination concurrently. Thus, the GMAP effectively protects the proliferation of bone marrow mesenchymal stem cells (BMSCs) under adverse high-glucose conditions. Furthermore, it also promotes the osteogenic differentiation and paracrine capabilities of BMSCs, and subsequently inhibits inflammation and enhances angiogenesis. In vivo diabetic rats bone defect model, it is demonstrated that GMAP microspheres significantly improve bone regeneration, as verified by micro-computed tomography and histological examinations. This study provides a novel strategy for bone regeneration by modulating the diabetic microenvironment, presenting a promising approach for addressing the complex challenges associated with bone healing in diabetic patients.

Cu/Gd co-doped hydroxyapatite/poly lactic-co-glycolic acid composites enhance MRI imaging and bone defect regeneration.

Background: The hydroxyapatite (HA)/poly(lactide-co-glycolide) acid (PLGA) composite material is a widely used orthopedic implant due to its excellent biocompatibility and plasticity. Recent advancements in cation doping have expanded its potential biological applications. However, conventional HA/PLGA composites are not visible under X-rays post-implantation and have limited osteogenic induction capabilities. Copper (Cu) is known to regulate osteoblast proliferation and differentiation, while gadolinium (Gd) can significantly enhance the magnetic resonance imaging (MRI) capabilities of materials. Methods: This study aimed to investigate whether incorporating Cu and Gd into an HA/PLGA composite could enhance the osteogenic properties, in vivo bone defect repair, and MRI characteristics. We prepared a Cu/Gd@HA/PLGA composite and assessed its performance. Results: Material characterization confirmed that Cu/Gd@HA retained the morphology and crystal structure of HA. The Cu/Gd@HA/PLGA composite exhibited excellent nuclear magnetic imaging capabilities, porosity, and hydrophilicity, which are conducive to cell adhesion and implant detection. In vitro experiments demonstrated that the Cu/Gd@HA/PLGA composite enhanced the proliferation, differentiation, and adhesion of MC3T3-E1 cells, and upregulated COL-1 and BMP-2 expression at both gene and protein levels. In vivo studies showed that the Cu/Gd@HA/PLGA composite maintained strong T1-weighted MRI signals and significantly improved the bone defect healing rate in rats. Conclusion: These findings indicate that the Cu/Gd@HA/PLGA composites significantly enhance T1-weighted MRI capabilities, promote osteoblast proliferation and differentiation in vitro, and accelerate bone defect healing in vivo.

Copper ions-photo dual-crosslinked alginate hydrogel for angiogenesis and osteogenesis.

Early healing of bone defects is still a clinical challenge. Many bone-filling materials have been studied, among which photocrosslinked alginate has received significant attention due to its good biocompatibility and morphological plasticity. Although it has been confirmed that photocrosslinked alginate can be used as an extracellular matrix for 3D cell culture, it lacks osteogenesis-related biological functions. This study constructed a copper ions-photo dual-crosslinked alginate hydrogel scaffold by controlling the copper ion concentration. The scaffolds were shaped by photocrosslinking and then endowed with biological functions by copper ions crosslinking. According to in vitro research, the dual-crosslinked hydrogel increased the compressive strength and favored copper dose-dependent osteoblast differentiation and cell surface adherence of rat bone marrow mesenchymal stem cells and the expression of type I collagen (Col1), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), vascular endothelial growth factor (VEGF). In addition, hydrogel scaffolds were implanted into rat skull defects, and more angiogenesis and osteogenesis could be observed in in vivo studies. The above results show that the copper-photo-crosslinked hydrogel scaffold has excellent osseointegration properties and can potentially promote angiogenesis and early healing of bone defects, providing a reference solution for bone tissue engineering materials.

Carvacrol-loaded premixed calcium phosphate bone cements with exceptional osteogenic and antibacterial properties to heal infected bone defects

The healing of infected bone fractures represents a significant clinical challenge in orthopedic surgery. Calcium phosphate cements (CPCs) are attractive materials, highly applicable in bone healing due to their satisfactory biological properties and chemical similarity to bone minerals. However, manual mixing is often required before localized application of conventional CPCs, increasing the risk of infection. Moreover, their antibacterial properties are often insufficient for treating infected fractures. In this study, antimicrobial two-paste premixed CPCs loaded with carvacrol were developed. The influence of the carvacrol on the setting properties and mechanical strength of the cement was studied. In vitro studies demonstrated the biocompatibility, osteogenic potential, and broad-spectrum antimicrobial efficacy of the premixed bone cements, including effectiveness against gram-positive, gram-negative, and drug-resistant bacteria. Notably, in vivo studies revealed exceptional antimicrobial and osteogenic properties of the carvacrol-loaded cements, confirming the promising potential of the premixed cements for the healing of infected bone defects.