Improve Bone Regeneration Research Articles

Application of Nanotechnology in Regenerative Medicine

The field of medicine has witnessed revolutionary changes in recent years due to rapid advancements in science and technology. Among these transformations, nanotechnology has emerged as a highly promising tool with significant potential for revolutionizing various aspects of healthcare. This paper provides a comprehensive review of the application of nanotechnology in the field of regenerative medicine, with particular emphasis on its impact on bone and skin remodeling. By leveraging the unique properties of nanomaterials, such as their high surface area-to-volume ratio and ability to interact with biological systems at the molecular level, researchers have been able to enhance the effectiveness of regenerative treatments. In bone remodeling, nanotechnology facilitates better integration of implants and promotes the differentiation of stem cells into osteoblasts, leading to improved bone regeneration. Similarly, in skin remodeling, nanomaterials contribute to accelerated wound healing, enhanced collagen deposition, and reduced scarring. These advancements not only improve the outcomes of traditional regenerative therapies but also open new avenues for developing more efficient and targeted approaches to tissue engineering.

Umbilical cord mesenchymal stem cells improve bone regeneration in diabetes mellitus animal model with apical periodontitis

BackgroundPrevious studies revealed diabetes mellitus subjects tend to have persistent apical periodontitis. Regenerative stem cells therapy through endodontic procedure is hoped to be a solution. This study assessed bone regeneration in diabetic rats with apical periodontitis through histopathological analysis of osteoblasts and immunohistochemical analysis of runt-related transcription factor 2 (Runx2) and Osterix. MethodsDiabetes mellitus and apical periodontitis was induced on 20 rats. Apical periodontitis was induced on mandibular right first molars under anesthesia. The teeth were left open for 7 days following access cavity and pulp extirpation, then the rats’ teeth were endodontically treated and randomly allocated into 4 groups (5 rats per group). The first and second groups was ended at 30 days (C30) and 60 days (C60) and labelled as control. The third and fourth groups was given umbilical cord mesenchymal stem cells and ended at 30 days (T30) and 60 days (T60). The osteoblasts, Runx2 and Osterix were analyzed. ANOVA and Tukey HSD tests were used for analysis. Differences with p values < 0.05 were considered significant. ResultsThe number of osteoblasts in the apical area in control groups (C30 and C60) and treatment groups (T30 and T60) showed a significant increase (p < 0.05). The expressions of Runx2 and Osterix in osteoblasts showed a significant increase among the control (C30 and C60) and treatment groups (T30 and T60) (p < 0.05). ConclusionUmbilical cord mesenchymal stem cells improve bone regeneration in diabetic animal model with apical periodontitis, in terms of osteoblasts, Runx2 and Osterix.

Cordycepin‐Loaded Dental Pulp Stem Cell‐Derived Exosomes Promote Aged Bone Repair by Rejuvenating Senescent Mesenchymal Stem Cells and Endothelial Cells

AbstractAging impairs bone marrow mesenchymal stem cell (BMSC) functions as well as associated angiogenesis which is critical for bone regeneration and repair. Hence, repairing bone defects in elderly patients poses a formidable challenge in regenerative medicine. Here, the engineered dental pulp stem cell‐derived exosomes loaded with the natural derivative of adenosine Cordycepin (CY@D‐exos) are fabricated by means of the intermittent ultrasonic shock, which dually rejuvenates both senescent BMSCs and endothelial cells and significantly improve bone regeneration and repair in aged animals. CY@D‐exos can efficiently overcome the senescence of aged BMSCs and enhance their osteogenic differentiation by activating NRF2 signaling and maintaining heterochromatin stability. Importantly, CY@D‐exos also potently overcomes the senescence of vascular endothelial cells and promotes angiogenesis. In vivo injectable gelatin methacryloyl (GelMA) hydrogels with sustained release of CY@D‐exos can accelerate bone injury repair and promote new blood vessel formation in aged animals. Taken together, these results thus demonstrate that cordycepin‐loaded dental pulp stem cell‐derived exosomes display considerable potential to be developed as a next‐generation therapeutic agent for promoting aged bone regeneration and repair.

Quality Improvement on Mechanical Properties of FDM 3D Printed Triply Periodic Minimal Surfaces (TPMS) Structure for Tissue Engineering Scaffold

Bone tissue engineering is the best alternative to treat large-scale bone defects by developing a scaffold. Many attempts have been made, but mechanical properties are still a significant concern in producing a feasible scaffold. This study aims to optimize the parameters of Fused Deposition Modeling (FDM) 3D printing, specifically layer thickness, flow rate, filling density, and filling pattern. The objective was to improve the compressive strength and Young's modulus of the scaffolds, which are crucial for the effective regeneration of bone tissue. Through this study, it has been found that the significant parameters to develop a feasible scaffold are layer thickness, flow rate, and filling density. By optimizing the parameters to a layer thickness of 0.05 mm, a flow rate of 50%, and a filling density of 100%, the resulting scaffolds exhibited a compressive strength of 0.8329 MPa and a Young's modulus of 16.42 MPa. These values exhibit extraordinary mechanical durability. The study's importance lies in its contribution to advancing more efficient bone scaffolds. These tailored scaffolds, which balance mechanical strength and biological functions, can potentially enhance bone repair and regeneration. This study establishes a foundation to produce more dependable and effective scaffolds, ultimately improving bone regeneration treatments.

Improvement of osteogenic differentiation potential of placenta-derived mesenchymal stem cells by metformin via AMPK pathway activation

BackgroundPlacenta-derived human mesenchymal stem cells (PL-MSCs) have gained a lot of attention in the field of regenerative medicine due to their availability and bone-forming capacity. However, the osteogenic differentiation capacity of these cells remains inconsistent and could be improved to achieve greater efficiency. Although metformin, a widely used oral hypoglycemic agent, has been shown to increase bone formation in various cell types, its effect on osteogenic differentiation of PL-MSCs has not yet been investigated. Therefore, the objective of this study was to examine the effect of metformin on the osteogenic differentiation capacity of PL-MSCs and the underlying mechanisms.MethodsThe PL-MSCs were treated with 0.5 to 640 µM metformin and their osteogenic differentiation capacity was examined by an alkaline phosphatase (ALP) activity assay, Alizarin red S staining and expression levels of osteogenic genes. The role of adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling in mediating the effect of metformin on the osteogenic differentiation capacity of PL-MSCs was also investigated by determining levels of phosphorylated AMPK (pAMPK)/AMPK ratio and by using compound C, an AMPK inhibitor.ResultsThe results showed that 10–160 µM metformin significantly increased the viability of PL-MSCs in a dose- and time-dependent manner. Furthermore, 80–320 µM metformin also increased ALP activity, matrix mineralization, and expression levels of osteogenic genes, runt-related transcription factor 2 (RUNX2), osterix (OSX), osteocalcin (OCN) and collagen I (COL1), in PL-MSCs. Metformin increases osteogenic differentiation of PL-MSCs, at least in part, through the AMPK signaling pathway, since the administration of compound C inhibited its enhancing effects on ALP activity, matrix mineralization, and osteogenic gene expression of PL-MSCs.ConclusionsThis study demonstrated that metformin at concentrations of 80–320 μM significantly enhanced osteogenic differentiation of PL-MSCs in a dose- and time-dependent manner, primarily through activation of the AMPK signaling pathway. This finding suggests that metformin could be used with other conventional drugs to induce bone regeneration in various bone diseases. Additionally, this study provides valuable insights for future osteoporosis treatment by highlighting the potential of modulating the AMPK pathway to improve bone regeneration.

GelMA hydrogels reinforced by PCL@GelMA nanofibers and bioactive glass induce bone regeneration in critical size cranial defects

BackgroundThe process of bone healing is complex and involves the participation of osteogenic stem cells, extracellular matrix, and angiogenesis. The advancement of bone regeneration materials provides a promising opportunity to tackle bone defects. This study introduces a composite hydrogel that can be injected and cured using UV light.ResultsHydrogels comprise bioactive glass (BG) and PCL@GelMA coaxial nanofibers. The addition of BG and PCL@GelMA coaxial nanofibers improves the hydrogel’s mechanical capabilities (353.22 ± 36.13 kPa) and stability while decreasing its swelling (258.78 ± 17.56%) and hydration (72.07 ± 1.44%) characteristics. This hydrogel composite demonstrates exceptional biocompatibility and angiogenesis, enhances osteogenic development in bone marrow mesenchymal stem cells (BMSCs), and dramatically increases the expression of critical osteogenic markers such as ALP, RUNX2, and OPN. The composite hydrogel significantly improves bone regeneration (25.08 ± 1.08%) in non-healing calvaria defects and promotes the increased expression of both osteogenic marker (OPN) and angiogenic marker (CD31) in vivo. The expression of OPN and CD31 in the composite hydrogel was up to 5 and 1.87 times higher than that of the control group at 12 weeks.ConclusionWe successfully prepared a novel injectable composite hydrogel, and the design of the composite hydrogels shows significant potential for enhancing biocompatibility, angiogenesis, and improving osteogenic and angiogenic marker expression, and has a beneficial effect on producing an optimal microenvironment that promotes bone repair.

Enhanced bone tissue regeneration via mesenchymal stem cells-laden Alginate/GelMa 3D-Bioprinted scaffold treated with Haplophyllum tuberculatum extract

Background and aimRegeneration of critical-sized bone defects is challenging due to avascular necrosis, inflammation, and disrupted osteogenesis. This study explores the synergistic effects of Haplophyllum tuberculatum (HT) extract and mesenchymal stem cells (MSCs) in an Alg/GelMa 3D-bioprinted scaffold to enhance bone regeneration. MethodsEthanolic extracts of stems (HTS), flowers (HTF), and a mixture (HTM) were obtained via Soxhlet extraction and subsequently characterized. Further investigations into their cytotoxicity, osteogenic and bone tissue regeneration potential were conducted, in vitro and in vivo. ResultsAlongside GC-MS analysis, vitamin and elemental analyses of HTS, HTF, and HTM revealed varying concentrations of key elements essential for bone regeneration. All extracts exhibited moderate antioxidant activity, with more potency in the HTF group. Cytotoxicity assays indicated the lack of cytotoxic effects from HTS and HTF on MSCs. The calcium secretion and deposition on MSCs revealed the osteogenic potential of HTF and HTM. Gene and protein expression analyses indicated significant upregulation of osteogenic markers in HTF-treated MSCs. The integration of MSCs into a Alg/GelMa 3D-bioprinted scaffold enhanced their viability and proliferation, validating its biocompatibility. Additionally, HTF promoted calcium deposition and ALP activity in the MSC-laden 3D-bioprinted scaffold. In vivo assessment in a rat calvarial defect model, demonstrated accelerated bone regeneration with HTF-treated scaffolds. The improved bone regeneration, vascularization, and collagen formation in HTF-treated defects were confirmed by histopathology results. ConclusionThis study underscores the significant role of the HTF in promoting osteogenesis, advocating for its incorporation into advanced tissue engineering strategies for bone regeneration.

Evaluation of Crestal Bone Loss after Placement of Bone Graft around the Oral Implant with/without Platelet-rich Plasma.

The current investigation aimed to evaluate the crestal bone loss after placement of bone graft around the oral implant with/without platelet-rich plasma (PRP). Forty patients seeking for crown supported by dental implants to replace at least one lost tooth were included in the present study. The participants were divided into two groups at random (n = 20): Group I: Received tricalcium phosphate (TCP) along with PRP and group II: Received TCP without PRP. Digital radiographs were used to quantify the crestal bone levels on the mesial, distal, buccal, and lingual side of each implant after surgery, also at 3 months and 6 months follow-up period. Data were recorded and subjected to statistical analysis. After 3 months, the crestal bone level in TCP with PRP group, mesial side was 1.02 ± 0.18, distal was 1.14 ± 0.11, buccal was 1.18 ± 0.12 and lingual was 1.16 ± 0.16. In only TCP group, mesial side was 1.14 ± 0.02, distal was 1.24 ± 0.10, buccal was 1.38 ± 0.12 and lingual was 1.30 ± 0.08. There was a statistically significant difference between the two groups. After 6 months, the crestal bone level in TCP with PRP group, mesial side was 1.26 ± 0.02, distal was 1.38 ± 0.14, buccal was 1.44 ± 0.09, and lingual was 1.52 ± 0.12. In only TCP group, mesial side was 1.40 ± 0.10, distal was 1.56 ± 0.12, buccal was 1.62 ± 0.06, and lingual was 1.84 ± 0.04. There was a statistically significant difference between the two groups at 3 and 6 months. On conclusion, considerable crestal bone loss was observed in both treatment regimens. But TCP bone graft with PRP group found decreased bone loss around the dental implants than only TCP bone graft group. The most important aspects of controlling crestal bone loss are choosing the right implant design and bone transplant materials. Also, platelet-rich fibrin plays an important role in accelerating the healing process, improving bone regeneration, and repairing as it contains a high amount of growth factors and inflammatory chemicals. How to cite this article: Jalaluddin M, Awasthi A, Aljulayfi IS, et al. Evaluation of Crestal Bone Loss after Placement of Bone Graft around the Oral Implant with/without Platelet-rich Plasma. J Contemp Dent Pract 2024;25(7):645-648.

Reduced Graphene Oxide-Substituted Nanohydroxyapatite: Rejuvenating Bone-Nerve Crosstalk with Electrical Cues in a Fragility Fracture Rat Model under Hyperglycemia.

Diabetes has currently acquired the status of epidemic worldwide, and among its various pathological consequences like retinopathy and nephropathy, bone fragility fractures from diabetic osteopathy occurs in later stages and is equally destructive. Chronic hyperglycemia culminates into deteriorating microvasculature and quality of bone, making it prone to fractures. Among these, hip fractures are most common, especially in older diabetic patients apart from underlying neuropathy. Our study is an attempt to ameliorate hip fragility fracture and nerve trauma with electrical stimulation as an interface in a chronic diabetic rat model. We have fabricated reduced graphene oxide-substituted hydroxyapatite as an electroactive bone substitute and incorporated it into chitosan gelatin cryogels. The in situ reduction of graphene oxide during sintering of hydroxyapatite imparts higher potential to the fabricated composite in dealing with problem at question. The cryogels depicted optimum in vitro biocompatibility and enhanced mineralization after ectopic subcutaneous implantation in rats. The therapeutic potency of composite cryogels was evaluated in a hip fracture model with compression to the sciatic nerve in diabetic rats, mimicking the severe clinical trauma. The presence of cryogels in the femoral neck canal coupled with electrical stimulation and biochemical factors significantly improved bone regeneration in diabetic rats as depicted with microcomputed tomography analysis and histology images. The application of electrical stimulation also ameliorated the nerve trauma observed with 70% improvement in electrophysiological parameters such as the compound muscle action potential with combinatorial therapy. We therefore report the successful implication of a multitarget therapy in a chronic diabetic rat model unraveling the bone-nerve crosstalk with electroactive smart cryogels.

Therapeutic Potential of Stearoyl-CoA Desaturase1 (SCD1) in Modulating the Effects of Fatty Acids on Osteoporosis.

Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in these patients is slow, making complete healing difficult. Along with the decline in bone volume and density, osteoporosis is characterized by an increase in marrow adipose tissue (MAT), which is fat within the bone. In this altered bone microenvironment, osteoblasts are influenced by various factors secreted by adipocytes. Notably, saturated fatty acids promote osteoclast activity, inhibit osteoblast differentiation, and induce apoptosis, further reducing osteoblast formation. In contrast, monounsaturated fatty acids inhibit osteoclast formation and mitigate the apoptosis caused by saturated fatty acids. Leveraging these properties, we aimed to investigate the effects of overexpressing stearoyl-CoA desaturase 1 (SCD1), an enzyme that converts saturated fatty acids into monounsaturated fatty acids, on osteogenic differentiation and bone regeneration in both in vivo and in vitro models. Through this novel approach, we seek to develop a stem cell-based therapeutic strategy that harnesses SCD1 to improve bone regeneration in the adipocyte-rich osteoporotic environment.

Proanthocyanidins modification of the mineralized collagen scaffold based on synchronous self-assembly/mineralization for bone regeneration

Proteoglycans (PG) is crucial for regulating collagen formation and mineralization during bone tissue development. A wide variety of PG-modified collagen scaffolds have been proposed for bone engineering application to promote biological responses and work as artificial matrices that guide tissue regeneration. However, poor performance of theses biomaterials against infections has led to an unmet need for clinical prevention. Therefore, we utilized proanthocyanidins (PA) to simulate the functions of PG, including mediating the collagen assembly and intrafibrillar mineralization, to optimize scaffolds performance. The excellent antibacterial properties of PA can endow the scaffolds with anti-infection effects in the process of tissue regeneration. When PA was added during fibrillogenesis, the collagen fibrils appeared irregular aggregation and the mineralization degree was reduced. In contrast, the addition of PA after collagen self-assembly improved the latter’s ability to act as a deposition template and remarkably promoted mineral ions infiltration, thus enhancing intrafibrillar mineralization. The PA-modified scaffold displayed a highly hydrophilicity behaviour and long-term resistance to degradation. The sustained release of PA effectively inhibited the activity of Staphylococcus aureus. The scaffold also showed excellent biocompatibility and improved bone regeneration in calvarial critical-size defect models. The application of PA enables a dual-function scaffold with favourable intrafibrillar mineralization and anti-bacterial properties for bone regeneration.

Intelligent Supramolecular Modification for Implants: Endogenous Regulation of Bone Defect Repair in Osteoporosis.

Addressing osteoporosis-related bone defects, a supramolecular strategy is innovated for modifying carbon fiber reinforced polyether ether ketone (CF/PEEK) composites. By covalently attaching intelligent macromolecules via in situ RAFT polymerization, leveraging the unique pathological microenvironment in patients with iron-overloaded osteoporosis, intelligent supramolecular modified implant surface possesses multiple endogenous modulation capabilities. After implantation, surface brush-like macromolecules initially resist macrophage adhesion, thereby reducing the level of immune inflammation. Over time, the molecular chains undergo conformational changes due to Fe (III) mediated supramolecular self-assembly, transforming into mechanistic signals. These signals are then specifically transmitted to pre-osteoblast cell through the binding capacity of the KRSR short peptide at the molecular terminus, induced their osteogenic differentiation via the YAP/β-catenin signaling axis. Furthermore, osteoblasts secrete alkaline phosphatase (ALP), which significantly hydrolyzes phosphate ester bonds in surface macromolecular side groups, resulting in the release of alendronate (ALN). This process further improves the local osteoporotic microenvironment. This intelligent surface modification tailors bone repair to individual conditions, automatically realize multiple endogenous regulation once implanted, and truly realize spontaneous activation of a series of responses conducive to bone repair in vivo. It is evidenced by improved bone regeneration in iron-overloaded osteoporotic rabbits and supported by in vitro validations.

Multimodal analyses of immune cells during bone repair identify macrophages as a therapeutic target in musculoskeletal trauma

Musculoskeletal traumatic injuries (MTI) involve soft tissue lesions adjacent to a bone fracture leading to fibrous nonunion. The impact of MTI on the inflammatory response to fracture and on the immunomodulation of skeletal stem/progenitor cells (SSPCs) remains unknown. Here, we used single-nucleus transcriptomic analyses to describe the immune cell dynamics after bone fracture and identified distinct macrophage subsets with successive pro-inflammatory, pro-repair and anti-inflammatory profiles. Concurrently, SSPCs transition via a pro- and anti-inflammatory fibrogenic phase of differentiation prior to osteochondrogenic differentiation. In a preclinical MTI mouse model, the injury response of immune cells and SSPCs is disrupted leading to a prolonged pro-inflammatory phase and delayed resolution of inflammation. Macrophage depletion improves bone regeneration in MTI demonstrating macrophage involvement in fibrous nonunion. Finally, pharmacological inhibition of macrophages using the CSF1R inhibitor Pexidartinib ameliorates healing. These findings reveal the coordinated immune response of macrophages and skeletal stem/progenitor cells as a driver of bone healing and as a primary target for the treatment of trauma-associated fibrosis.

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.

Osteoinductivity enhancement by tailoring the surface chemical bond status: A strategy to mobilize host bone growth factors for in situ bone regeneration

The incorporation of growth factors and biomaterials is a promising strategy for improving osseointegration. However, current strategies to develop biomaterials with exogenous growth factors present disadvantages like inefficiency, difficult deployment, and potential off-target activation, making their translation into clinical practice challenging. This study reveals a bioactive N-doped tantalum carbide (TaC) solid solution film that can be used to construct a TaCN film via bionic interface engineering to recruit host bone growth factors to the wounded site and improve bone regeneration. X-ray photoelectron spectroscopy (XPS) and protein absorption analysis reveal that the performance of TaCN is related to the surface chemical bonds of films. The introduction of N to TaC causes a cascade effect wherein negative charges enrich on the TaCN surface, and the recruitment of positively charged bone growth factors around the TaCN film is facilitated. Under these circumstances, the endogenous bone growth factors enhance bone healing. The TaCN film shows an outstanding performance for in vivo osteogenic differentiation along with a superior in vitro cytocompatibility. Incorporation of N atoms into TaC provides a new clinically translatable strategy to mobilize host bone growth factors for in situ bone regeneration without the need for incorporation of exogenous growth factors.

Role of Statins in Oral and Maxillofacial Surgery: A Literature Review.

In recent years, there has been a notable increase in interest in the use of statins in oral and maxillofacial surgery. The purpose of this literature review was to look into the effectiveness of statins in this area. Using a set of keywords, a thorough search of electronic databases was carried out, including PubMed, Scopus, Web of Science, Excerpta Medica database (EMBASE), and ProQuest. The papers considered were just those published in the English language between January 2012 and January 2024. Only human studies were taken into consideration; those involving animals were not. For the final analysis that assessed the use of statins in dentistry, a total of 30 papers were chosen. The designs, sample sizes, and materials employed in the experiments varied. According to the research, statins improve bone regeneration, have antiviral and antibacterial qualities, and work well as a therapeutic adjuvant for the treatment of periodontal disease. The analysis of the literature indicates that statins may be beneficial for treating periodontal disease, promoting bone regeneration, and improving oral health in the context of oral and maxillofacial surgery. Nevertheless, more investigation is required to completely comprehend the function of statins in this domain.

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.

GAPDH-Silence Microsphere via Reprogramming Macrophage Metabolism and eradicating Bacteria for Diabetic infection bone regeneration

Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.

Potential plausible role of Wharton's jelly mesenchymal stem cells for diabetic bone regeneration.

This letter addresses the review titled "Wharton's jelly mesenchymal stem cells: Future regenerative medicine for clinical applications in mitigation of radiation injury". The review highlights the regenerative potential of Wharton's jelly mesenchymal stem cells (WJ-MSCs) and describes why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine. The potential plausible role of WJ-MSCs for diabetic bone regeneration should be noticeable, which will provide a new strategy for improving bone regeneration under diabetic conditions.

The role of collagen and crystallinity in the physicochemical properties of naturally derived bone grafts

Abstract Xenografts are commonly used for bone regeneration in dental and orthopaedic domains to repair bone voids and other defects. The first-generation xenografts were made through sintering, which deproteinises them and alters their crystallinity, while later xenografts are produced using cold-temperature chemical treatments to maintain the structural collagen phase. However, the impact of collagen and the crystalline phase on physicochemical properties have not been elucidated. We hypothesized that understanding these factors could explain why the latter provides improved bone regeneration clinically. In this study, we compared two types of xenografts, one prepared through a low-temperature chemical process (Treated) and another subsequently sintered at 1100 °C (Sintered) using advanced microscopy, spectroscopy, x-ray analysis, and compressive testing. Our investigation showed that the Treated bone graft was free of residual blood, lipids, or cell debris, mitigating the risk of pathogen transmission. Meanwhile, the sintering process removed collagen and the carbonate phase of the Sintered graft, leaving only calcium phosphate and increased mineral crystallinity. Micro computed tomography revealed that the Treated graft exhibited an increased high porosity (81%) and pore size compared to untreated bone, whereas the Sintered graft exhibited shrinkage, which reduced the porosity (72%), pore size, and strut size. Additionally, scanning electron microscopy (SEM) displayed crack formation around the pores of the Sintered graft. The Treated graft displayed median mechanical properties comparable to native cancellous bone and clinically available solutions, with an apparent modulus of 166 MPa, yield stress of 5.5 MPa, and yield strain of 4.9%. In contrast, the Sintered graft exhibited a lower median apparent modulus of 57 MPa. It failed in a brittle manner at a median stress of 1.7 MPa and strain level of 2.9%, demonstrating the structural importance of the collagen phase. This indicates why bone grafts prepared through cold-temperature processes are clinically favourable.