Regeneration Of Defects Research Articles

Axolotl mandible regeneration occurs through mechanical gap closure and a shared regenerative program with the limb.

The mandible plays an essential part in human life and, thus, defects in this structure can dramatically impair the quality of life in patients. Axolotls, unlike humans, are capable of regenerating their lower jaws; however, the underlying mechanisms and their similarities to those in limb regeneration are unknown. In this work, we used morphological, histological and transcriptomic approaches to analyze the regeneration of lateral resection defects in the axolotl mandible. We found that this structure can regenerate all missing tissues in 90 days through gap minimization, blastema formation and, finally, tissue growth, differentiation and integration. Moreover, transcriptomic comparisons of regenerating mandibles and limbs showed that they share molecular phases of regeneration, that these similarities peak during blastema stages and that mandible regeneration occurs at a slower pace. Altogether, our study demonstrates the existence of a shared regenerative program used in two different regenerating body structures with different embryonic origins in the axolotl and contributes to our understanding of the minimum requirements for a successful regeneration in vertebrates, bringing us closer to understand similar lesions in human mandibles.

Hybrid zinc oxide nanocoating on titanium implants: Controlled drug release for enhanced antibacterial and osteogenic performance in infectious conditions

Implant-associated bacterial infections are a primary cause of complications in orthopedic implants, and localized drug delivery represents an effective mitigation strategy. Drawing inspiration from the morphology of desiccated soil, our group has developed an advanced drug-delivery system augmented onto titanium (Ti) plates. This system integrates zinc oxide (ZnO) nanorod arrays with a vancomycin drug layer along with a protective Poly(lactic-co-glycolic acid) (PLGA) coating. The binding between the ZnO nanorods and the drug results in attached drug blocks, isolated by desiccation-like cracks, which are then encapsulated by PLGA to enable sustained drug release. Additionally, the release of zinc ions and the generation of reactive oxygen species (ROS) from the ZnO nanorods enhance the antibacterial efficacy. The antibacterial properties of ZnO nanorod-drug-PLGA system have been validated through both in vitro and in vivo studies. Comprehensive investigations were conducted on the impact of bacterial infections on bone defect regeneration and the role of this drug-delivery system in the healing process. Furthermore, the local immune response was analyzed and the immunomodulatory function of the system was demonstrated. Overall, the findings underscore the superior performance of the ZnO nanorod-drug-PLGA system as an efficient and safe approach to combat implant-associated bacterial infections. Statement of significanceImplant-associated bacterial infections pose a significant clinical challenge, particularly in orthopedic procedures. To address this, we developed an innovative ZnO nanorod-drug-PLGA system for local antibiotic delivery on conventional titanium implants. This system is biodegradable and features a unique desiccation-like structure that enables sustained drug release, along with the active substances released from the ZnO nanorods. In a rat calvarial defect model challenged with S. aureus, our system demonstrated remarkable antibacterial efficacy, significantly enhanced bone defect regeneration, and exhibited local immunomodulatory effects that support both infection control and osteogenesis. These breakthrough findings highlight the substantial clinical potential of this novel drug delivery system and introduce a transformative coating strategy to enhance the functionality of traditional metallic biomaterials.

Bone regeneration by a bone substitute biomaterial containing hydroxyapatite, chitosan, xanthan and graphene oxide supplemented with conditioned medium from mesenchymal stem cells.

This study analyzed a recently developed bone substitute biomaterial made of chitosan-xanthanhydroxyapatite-graphene oxide (CXHAG). The CXHAG particles underwent in vitro structural and morphological characterization, and in vivo testing with or without osteogenic conditioned medium from mesenchymal stem cells. Aim: The aim of this study was to determine whether the CXHAG novel biomaterial, supplemented with conditioned medium from mesenchymal stem cells, could be useful for bone regeneration. Materials and Method: For the in vitro study, cells were incubated with 20mg of CXHAG granules for 24 hours and a MTT assay was performed to tests for cytotoxicity. For the in vivo study, critical size calvarial bone defects were created in twenty-five rats. One animal had the defect unfilled (Control Group-CG) and was euthanized after 42 days. Twelve rats received the CXHAG particles (Group 1-G1) and the other twelve received the CXHAG particles supplemented with the conditioned medium (Group 2-G2). All G1/G2 grafts were covered with a CXHAG membrane. G1/G2 animals were euthanized after 14 days (T1) or 42 days (T2). The specimens were processed and histologically evaluated. Results: SEM analysis of the CXHAG particles showed granules of 300-400μm, with a rough irregular surface. They were not cytotoxic to dental pulp stem cells in vitro. The CG specimen showed loose immature connective tissue and no bone formation at the center of the defect. G1 and G2 presented remnant biomaterial particles at both time points, but only G2 had bone formation at the enter of the defect. Conclusions: The conditioned medium had a positive effect on bone regeneration in rat calvarial critical size defects when associated with the novel bone substitute biomaterial.

Applications of type I and II collagen in osteochondral tissue engineering: Respective features and future perspectives

At present, osteoarthritis stands as one of the most prevalent degenerative musculoskeletal diseases globally. The inherent lack of self-healing capacity in articular cartilage presents a considerable obstacle in treating osteoarthritis. Tissue engineering emerged as a promising strategy for the regeneration of osteochondral defects. Collagen, a primary component of bone and cartilage, stands out as a widely utilized natural material in osteochondral tissue engineering. Among various collagen types, Type I and type II collagen are notably prominent in this field. This review initially summarizes the advantageous and disadvantageous properties of type I/II collagen in osteochondral tissue engineering, proceeds to introduce their applications in this context, and concludes with a prospective outlook on the future development of type I/II collagen's applications.

Xenogenous implanted dental follicle stem cells promote periodontal regeneration through inducing the N2 phenotype of neutrophils

BackgroundPeriodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period.MethodsTo trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation.ResultsIn vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type macrophages, fewer TRAP + osteoclasts, and an upregulated OPG/RANKL ratio were detected in the E-DFSC group compared to the control group, which indicated that immune balance tilts towards healing and bone formation.ConclusionThe xenogenous implanted DFSCs can induce the N2 phenotype of neutrophils in the early stage, which can activate the innate immune mechanism of the host to promote periodontal tissue regeneration.

Evaluation of the effect of osteosynthesis wires on the structural reorganization of metaepiphyseal cartilage (an experimental and morphological study)

Introduction Premature arrest of bone growth is the most common complication of bone fractures at the growth plate level.The purpose of the work was to evaluate the structural reorganization of metaepiphyseal cartilage following its direct injury with metal and biodegradable wires in an experiment.Materials and methods The metaepiphyseal cartilage of the distal femur of 18 lambs of both sexes was studied. The age of the animals at the beginning of the study was (43.92 ± 0.8) days, by 60 and 120 days (102.63 ± 0.82) and (161.1 ± 0.9) days, respectively. The animals underwent transphyseal insertion of wires/ pins: series 1 — Kirschner wires, series 2 — titanium wires, series 3 — poly-L-lactic acid pins. The duration of the experiment was 60 and 120 days. Clinical and radiographic studies were carried out. Histomorphometry was performed using an AxioScope.A1 microscope and Zenblue software (CarlZeissMicroImagingGmbH, Germany).Results Reactive changes in the growth plate at the interface with the wire were manifested by proliferation of chondrocytes in the zone of proliferating cartilage and in the reserve zone; the minimally expressed changes were noted in series 2, the most pronounced were in series 1. By the end of the experiment, at the interface with the wire in series 1, blood vessels penetrated into the metaepiphyseal cartilage; in series 3 the amount of the fibrous component was increased, which indicates further formation of “bone bridges” and “fibrous bridges,” respectively. In undamaged areas of the growth plate in all series, the zonal structure was preserved. By the end of the experiment, increased values of the thickness of the metaepiphyseal cartilage were noted (1.2 times higher than the control), differences between series were a tendency; in series 2 and 3 the ratio of metaepiphyseal cartilage zones was comparable to the control; in series 1 the proportion of the proliferating cartilage zone was increased by 4 %.Discussion The main problem with growth plate injuries is the formation of bone tissue or fibrosis, which affects the growing process. Currently, the question of choosing a treatment tactic for growth plate injury depending on the size of the “bone bridges” is debatable. Relevant are future comparative studies of the regeneration of metaepiphyseal cartilage defects after the use of fixators made from different materials.Conclusion Histomorphometric characteristics of the growth zone reliably showed that the insertion of wires, regardless of their material, was not accompanied by inhibition of the bone-forming function of the distal metaepiphyseal cartilage of the femur.

Carbon fiber felt scaffold from Brazilian textile PANfiber for regeneration of critical size bone defects in rats: A histomorphometric and microCT study.

The objective of the present study was to evaluate the carbon fiber obtained from textile PAN fiber, in its different forms, as a potential scaffolds synthetic bone. Thirty-four adult rats were used (Rattus norvegicus, albinus variation), two critical sized bone defects were made that were 5 mm in diameter. Twenty-four animals were randomly divided into four groups: control (C)-bone defect + blood clot, non-activated carbon fiber felt (NACFF)-bone defect + NACFF, activated carbon fiber felt (ACFF)-bone defect + ACFF, and silver activated carbon fiber felt (Ag-ACFF)-bone defect + Ag-ACFF, and was observed by 15 and 60 days for histomorphometric, three-dimensional computerized microtomography (microCT) and mineral apposition analysis. On histomorphometric and microCT analyses, NACFF were associated with higher proportion of neoformed bone and maintenance of bone structure. On fluorochrome bone label, there was no differences between the groups. NACFF has shown to be a promising synthetic material as a scaffold for bone regeneration.

Construction of a Titanium-Magnesium Composite Internal Fixation System for Repairing Bone Defects.

The repair and regeneration of maxillofacial bone defects are major clinical challenges. Titanium (Ti)-magnesium (Mg) composites are a new generation of revolutionary internal fixation materials encompassing the mechanical strength and bioactive advantages of Ti and Mg alloys, respectively. This study was aimed to construct a Ti-Mg composite internal plate/screw fixation system to fix and repair bone defects. Further, the effects of different internal fixation systems on bone repair were analyzed through radiological and histological analyses. Notably, Ti6Al4V with rolled Mg foil was used as the experimental group, and a bone defect model of transverse complete amputation of the ulna in rabbits similar to the clinical condition was established. The internal fixation system with the highest osteogenic efficiency was selected based on in vivo results, and the direct and indirect bone repair abilities of the selected materials were evaluated in vitro. Notably, the thin Mg foil-Ti6Al4V internal fixation system exhibited the best fixation effect in the bone defect model and promoted the formation of new bone and early healing of bone defect areas. In vitro, the thin Mg foil-Ti6Al4V composite enhanced the activity of MC3T3-E1 cells; promoted the proliferation, adhesion, extension, and osteogenic differentiation of MC3T3-E1 cells; and regulated new bone formation. Further, it also promoted the polarization of RAW264.7 cells to M2 macrophages, induced the osteogenic immune microenvironment, and indirectly regulated the bone repair process. Therefore, a internal fixation system holds a promising potential for the internal fixation of maxillofacial bone defects. Our findings provide a theoretical and scientific basis for the design and clinical application of Ti-Mg internal fixation systems.

Initial experience with ovine forestomach matrix graft for glossectomy defect reconstruction: A case series

Soft tissue reconstruction of oral cavity defects, such as glossectomy defects secondary to malignancy, pose a challenge for head and neck, oral, and maxillofacial surgeons. Reconstruction options for mucosal defects include primary closure, healing by secondary intention, full mucosal and split-thickness skin grafts, pedicled flaps, and microvascular free flaps. Biological grafts have become an integral part of the modern reconstructive ladder and are widely used for the regeneration of various soft tissue defects, including oral defects. This case series describes our initial experience using ovine forestomach matrix grafts in tongue and oral cavity reconstruction. Oral reconstruction using ovine forestomach matrix grafts was undertaken on three patients post wide excision and resulted in good functional and cosmetic outcomes. The rate of tissue formation provided by the graft and the grafts’ relative resistance to the hostile environment of the oral cavity support further clinical research to validate the use of these devices in oral reconstruction.

ZIF-8-modified hydrogel sequentially delivers angiogenic and osteogenic growth factors to accelerate vascularized bone regeneration

To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NH2 nanoparticles (NPs) into a sodium alginate/hydroxyapatite/polyvinyl alcohol hydrogel loaded with PDGF-BB, allowing for the sequential release of angiogenic and osteogenic growth factors (GFs) during bone repair. ZIF-8 served as a protective host for BMP-2 from degradation, ensuring high encapsulation efficiency and long-term bioactivity. The SHPP-ZB hydrogel exhibited enhanced mechanical strength and injectability, making it suitable for complex bone defects. It provided a swelling interface for tissue interlocking and the early release of Zn2+ and tannin acid (TA) to exert antioxidant and antibacterial effects, followed by the sequential release of angiogenic and osteogenic GFs to promote high-quality vascularized bone regeneration. In vitro experiments demonstrated the superior angiogenic and osteogenic properties of SHPP-ZB compared to other groups. In vivo experiments indicated that the sequential delivery of GFs via SHPP-ZB hydrogel could improve vascularized bone regeneration. Further, RNA sequencing analysis of regenerative bone tissue revealed that SHPP-ZB hydrogel promoted vascularized bone regeneration by regulating JUN, MAPK, Wnt, and calcium signaling pathways in vivo. This study presented a promising approach for efficient vascularized bone regeneration in large-scale bone defects.

Assessment of Novel Surgical Procedures Using Bone Morphogenic Protein-7 Infused Into Decellularised Muscle and Bioactive Ceramic: A Histological Analysis.

Reconstruction of critical bone defects is considered a challenge due to vascular reperfusion injury that may occur. The present study hypothesized that the use of decellularized muscle scaffold (DMS) and bone morphogenic protein-7 (BMP-7), along with resorbable bioactive ceramic silica calcium phosphate cement (SCPC) seeded with human bone marrow stromal cells, can expedite bone formation and maturation. Surgical bone defects were created in 20 nude transgenic mice. In experimental group 1 (n = 10), a critical-size (4mm) calvarial defect was made and grafted with DMS-BMP-7/SCPC. In situ human bone marrow stromal cells [human mesenchymal stromal cells (hMSC)] were seeded thereafter. As a control, group 2 (n = 10) was treated with DMS/SCPC seeded with hMSCs. After 8 weeks, bone regeneration was evaluated using histology and histomorphometry for both groups. Histological examination showed bone regeneration crossing the gap (experimental group 1), bone regeneration was noted at the defect periphery, and scattered islands of bone at the canters of the defects (control group 2). New bone formation and maturation were superior in the groups treated with the DMS/BMP-7/SCPC/hMSC constructs. The quantitative histological assessment revealed that the average bone surface area was 255 ± 25mm2, which was 1.5 times the surface area of group 2, which was reported at 170 ± 35mm2. The reported difference was considered statistically significant (P < 0.05). The DMS-BMP-7/SCPC scaffold induced bone regeneration and neovascularization in critical-size defects.

Endodontic surgery and platelet concentrates: A comprehensive review.

While autologous platelet concentrates (APCs) have gained traction as promising regenerative materials in recent years, their impact on wound healing and tissue regeneration in periapical hard tissue defects remains controversial. Endodontic microsurgery (EMS) has embraced the potential of platelet concentrates, particularly L-PRF (Leucocyte-Platelet-Rich Fibrin) and PRP (Platelet-Rich Plasma), as regenerative tools. These concentrates, rich in growth factors and other bioactive molecules, are thought to enhance healing and treatment outcomes for various endodontic conditions. However, their effectiveness remains a subject of investigation. Despite encouraging 3-D cone beam computed tomography (CBCT) based evidence for PRP's effectiveness in complex lesions and apico-marginal defects, inconsistencies in its performance across preparation and application protocols raise questions about its superiority over existing options. More research is crucial to understand its full potential as a reliable regenerative tool in endodontics. L-PRF and its derivatives are particularly effective in treating apical-marginal defects. It enhances clinical attachment levels and reduces probing pocket depths, likely due to its slow and coordinated release of various growth factors. L-PRF has been shown to also improve patients' quality of life by reducing postoperative swelling and pain. However, more research is needed to standardize its preparation methods and confirm its long-term benefits. This paper aims to provide a comprehensive review of the current knowledge and recent advances in endodontic surgery and the use of platelet concentrates, focusing on their roles in managing periapical lesions and endo-perio lesions.

Evaluation of Peri-Implantitis Bone Defect Healing: Comparing the Efficacy of Small-Particle Dentin and Bio-Oss in Bone Density Attenuation.

Introduction: Peri-implantitis is a serious complication in dental implantology that, if left untreated, may lead to implant loss and systemic diseases. Effective regeneration of bone defects resulting from peri-implantitis is crucial to maintaining the functionality of dental implants. Purpose of the Study: The study aimed to compare the effectiveness of fine-particle dentin and Bio-Oss in the reconstruction of bone defects caused by peri-implantitis. Materials and Methods: The study included a comprehensive radiological assessment of changes in bone density over time. Bone density was assessed using Hounsfield Units (HUs) as a measure of bone attenuation, with radiological assessments performed at 8- and 12-week intervals during the healing process. The study included participants ranging in age from 30 to 65 years. Fifty-seven patients were divided into three groups: 22 patients received small-particle dentin, 15 received Bio-Oss, and 20 controls without bone substitute material. Results: The fine-dentin group showed a 20% increase in bone density after 8 weeks (p < 0.05), while the Bio-Oss group showed a 15% increase after 12 weeks (p < 0.05). The control group showed minimal changes in bone density (5% after 12 weeks), which was not statistically significant. Clinical evaluations showed 95% successful integration in the fine dentin group, 85% in the Bio-Oss group, and 70% in the control group. The fine-dentin group showed a 20% increase in bone density after 8 weeks (p < 0.05), while the Bio-Oss group showed a 15% increase after 12 weeks (p < 0.05). The control group showed minimal changes in bone density (5% after 12 weeks), which was not statistically significant. Clinical evaluations showed 95% successful integration in the fine-dentin group, 85% in the Bio-Oss group, and 70% in the control group. Conclusions: Both fine-particle dentin and Bio-Oss significantly improved bone density compared to the control group. Fine-particle dentin is suitable for immediate bone regeneration due to its rapid initial regeneration, while Bio-Oss provides long-term support, ideal for maintaining implant stability over a longer period of time. The results highlight the importance of selecting appropriate bone replacement materials depending on the clinical scenario to improve patient outcomes after dental implant placement.

Promotion of osteochondral repair through immune microenvironment regulation and activation of endogenous chondrogenesis via the release of apoptotic vesicles from donor MSCs

Utilizing transplanted human umbilical cord mesenchymal stem cells (HUMSCs) for cartilage defects yielded advanced tissue regeneration, but the underlying mechanism remain elucidated. Early after HUMSCs delivery to the defects, we observed substantial apoptosis. The released apoptotic vesicles (apoVs) of HUMSCs promoted cartilage regeneration by alleviating the chondro-immune microenvironment. ApoVs triggered M2 polarization in macrophages while simultaneously facilitating the chondrogenic differentiation of endogenous MSCs. Mechanistically, in macrophages, miR-100-5p delivered by apoVs activated the MAPK/ERK signaling pathway to promote M2 polarization. In MSCs, let-7i-5p delivered by apoVs promoted chondrogenic differentiation by targeting the eEF2K/p38 MAPK axis. Consequently, a cell-free cartilage regeneration strategy using apoVs combined with a decellularized cartilage extracellular matrix (DCM) scaffold effectively promoted the regeneration of osteochondral defects. Overall, new mechanisms of cartilage regeneration by transplanted MSCs were unconcealed in this study. Moreover, we provided a novel experimental basis for cell-free tissue engineering-based cartilage regeneration utilizing apoVs.

Utilization of a Cortical Xenogeneic Membrane for Guided Bone Regeneration: A Retrospective Case Series.

Background: Guided bone regeneration (GBR) is a reliable technique used in vertical and horizontal bone defects. The posterior mandibular region is an area limited by anatomic constraints. The use of resorbable membranes with a cortical component could compensate for the lack of rigidity of resorbable membranes without the complications of non-resorbable membranes. The aim of this study was to evaluate the mean bone gains of a xenogeneic cortical membrane in horizontal and vertical bone defects in comparison with other membranes in the literature. Methods: A porcine cortical membrane was used to perform 7 GBR in the posterior mandibular region of five patients. Preoperative (T0) and six months postoperative (T1) cone beam computed tomography were superimposed to measure the horizontal and vertical bone gain. Implants were positioned at all sites, six months after GBR. Complications and bone resorption around the implants were also documented. Results: The mean horizontal and vertical bone gains were 3.83 ± 1.41 mm and 4.17 ± 1.86 mm, respectively. The analysis of repeatability was 0.997. As many as 40% of patients experienced pain refractory to analgesics. No exposure or infectious phenomenon was observed. Conclusions: This xenogeneic cortical membrane seemed to provide interesting results in the regeneration of horizontal and vertical bone defects. Comparative and prospective studies are necessary to validate the effectiveness of this membrane.

Bone Regeneration of Rat Critical-Sized Calvarial Defects by the Combination of Photobiomodulation and Adipose-Derived Mesenchymal Stem Cells.

Introduction: This study explored the synergistic effects of low-level laser therapy (LLLT) and adipose-derived stem cells (ADSCs) on cranial bone regeneration in rats, addressing the limitations of autogenous grafts and advancing bone tissue engineering with innovative photobiomodulation (PBM) applications. Methods: Sixty Wistar rats were allocated to 5 separate groups randomly; (1) natural bovine bone mineral (NBBM); (2) NBBM+LLLT; (3) NBBM+allogenic ADSCs; (4) NBBM+allogenic ADSCs+LLLT; (5) Only defects. 8-mm calvarial defects were made in each rat in the surgical procedure. A diode laser was applied with the following parameters (continuous mode, power of 100mW, wavelength of 808nm, and 4 J/cm2 energy density) immediately after the procedure and every other day. Bone samples were obtained and assessed histomorphometrically and histologically after staining with hematoxylin and eosin (H&E). Results: Different volumes of bony material were observed in two weeks; 2.94%±1.00 in group 1, 5.1%±1.92 in group 2, 7.11%±2.82 in group 3, 7.34%±2.31 in group 4, and 2.01%±0.83 in group 5 (P<0.05). On the other hand, foreign body residuals were up by 23% in the groups with scaffolding by the end of 2 weeks. Four weeks of observation led to 6.74 %±1.95, 13.24%±1.98, 15.76%±1.19, 15.92%±3.4, and 3.11%±1.00 bone formation in groups 1 to 5, respectively (P<0.05). Generally, the difference between groups 2-4 was not statistically significant based on different types of bone and the extent of inflammation. Conclusion: Bearing in mind the limitations of our research, it was demonstrated that ADSCs in combination with PBM have promising effects on bone tissue regeneration in sizeable bony defects. Furthermore, this study also showed that PBM usage improved the newly regenerated bone quality.

Fibrin-konjac glucomannan-black phosphorus hydrogel scaffolds loaded with nasal ectodermal mesenchymal stem cells accelerated alveolar bone regeneration

BackgroundEffective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels.MethodsPrimary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration.ResultsThe addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p < 0.0001), osteocalcin (Ocn, p < 0.0001), type collagen (Col , p < 0.0001), bone morphogenetic protein-2 (Bmp2, p < 0.0001), Smad1 (p = 0.0006), and runt-related transcription factor 2 (Runx2, p < 0.0001) were all significantly upregulated.ConclusionsEMSCs/BPNs-containing fibrin-KGM hydrogels accelerated the recovery of the alveolar bone defect in rats by effectively up-regulating the expression of osteogenesis-related genes, promoting the formation and mineralisation of bone matrix.

3D-printed HA15-loaded β-Tricalcium Phosphate/Poly (Lactic-co-glycolic acid) Bone Tissue Scaffold Promotes Bone Regeneration in Rabbit Radial Defects.

In this study, a β-tricalcium phosphate (β-TCP)/poly (lactic-co-glycolic acid) (PLGA) bone tissue scaffold was loaded with osteogenesis-promoting drug HA15 and constructed by three-dimensional (3D) printing technology. This drug delivery system with favorable biomechanical properties, bone conduction function, and local release of osteogenic drugs could provide the basis for the treatment of bone defects. The biomechanical properties of the scaffold were investigated by compressive testing, showing comparable biomechanical properties with cancellous bone tissue. Furthermore, the microstructure, pore morphology, and condition were studied. Moreover, the drug release concentration, the effect of anti-tuberculosis drugs in vitro and in rabbit radial defects, and the ability of the scaffold to repair the defects were studied. The results show that the scaffold loaded with HA15 can promote cell differentiation into osteoblasts in vitro, targeting HSPA5. The micro-computed tomography scans showed that after 12 weeks of scaffold implantation, the defect of the rabbit radius was repaired and the peripheral blood vessels were regenerated. Thus, HA15 can target HSPA5 to inhibit endoplasmic reticulum stress which finally leads to promotion of osteogenesis, bone regeneration, and angiogenesis in the rabbit bone defect model. Overall, the 3D-printed β-TCP/PLGA-loaded HA15 bone tissue scaffold can be used as a substitute material for the treatment of bone defects because of its unique biomechanical properties and bone conductivity.

Bioactive poly(ethylene glycol)-chondroitin sulfate-triple helical recombinant collagen hydrogel for enhanced cranial defect repair

The reconstruction of critical-size calvarial defects remains a fundamental challenge. Recombinant collagen has gained significant attention in bone tissue engineering owing to its remarkable bioactivity and non-immunogenicity. Herein, we have for the first time developed a bioactive poly(ethylene glycol)-chondroitin sulfate-triple helical recombinant collagen (PEG-ChS-THRC) hydrogel for enhanced bone regeneration in cranial defects. A simple and mild crosslinking reaction of two-arm polyethylene glycol active ester (NHS-PEG-NHS), adipic dihydrazide modified chondroitin sulfate (ChS-ADH) and triple helical recombinant collagen (THRC) leads to the formation of the PEG-ChS-THRC hydrogel. The hydrogel demonstrates interconnected porous structures, enhanced mechanical strength, diminished swelling ratios and adjustable biodegradability. It possesses exceptional biocompatibility and bioactivity, significantly facilitating cell proliferation, adhesion, migration, and osteogenic differentiation of BMSCs. Micro-computed tomography (micro-CT), magnetic resonance imaging (MRI) and histological characterization of rat models with critical-size cranial defects have consistently demonstrated that the PEG-ChS-THRC hydrogel significantly promotes bone tissues regeneration. The innovative bioactive scaffold provides a remarkably improved remedy for critical-size cranial defects, holding greatly promising applications in the fields of bone tissue regeneration.Graphical

Modeling Electrochemical Vacancy Regeneration in Single-Walled Carbon Nanotubes.

Synthesis-induced defects in single-walled carbon nanotubes (SWCNTs) enable diverse catalytic reactions, but the nature of catalytic intermediates and how active species regeneration occurs are unclear. Using a quantum mechanics/molecular mechanics (QM/MM) hybrid methodology based on density functional theory (DFT) and a classical force-field, we explore the reactivity and electrochemical regeneration of a vacancy defect in a zigzag SWCNT. Our findings indicate that hydrolysis of the defect forms a ketone group on one carbon atom and C-H bonds on two adjacent carbons. Applying an electrochemical potential of ESHE = -0.740 V triggers a proton-coupled electron transfer (PCET), converting the ketone to a hydroxyl group. Further reduction at ESHE = -1.08 V induces another PCET, expelling the hydroxyl as water and forming an active carbon with carbene character that can react with hydrogen peroxide and perchlorate. The hydrogen atoms on neighboring carbons prevent further water dissociation, maintaining the catalytic vacancy.