Regeneration Of Defects Research Articles

Boron-Doped Nano Hydroxyapatite Grafts for Bone Regeneration in Rat Mandibular Defects.

The aim of this study was to evaluate the potential effects of boron-doped nano hydroxyapatite grafts on craniofacial bone regeneration in critical bone defects in the mandibular corpus of rats, in terms of scintigraphic and histopathological aspects. Forty Wistar albino rats, with an average weight of 200-220g, aged 16-18weeks, and all male, were used in the study. The rats were randomly assigned to five groups, each containing 8 rats, as follows: group C1 (no procedure applied to the mandible), group C2 (surgical defect created in the mandible but no treatment applied), group nHA (nano hydroxyapatite applied to the surgical defect area), group nHA + B1 (nano hydroxyapatite + 1% boron applied to the surgical defect area), and group nHA + B2 (nano hydroxyapatite + 2% boron applied to the surgical defect area). A standard 4 × 4mm full-thickness transosseous bone defect was created in the mandibular corpus of all rats, except for those in group C1. The bone defect in the rats in group C2 was left to heal naturally. Nano hydroxyapatite (nHA), nano hydroxyapatite + 1% boron, and nano hydroxyapatite + 2% boron were applied to the surgical defect areas of the other three groups, respectively. Bone scintigraphy was performed on all rats on days 0 (following the surgical procedure) and 28 of the experimental period. At the end of the 28th day, the animals were sacrificed, and tissue samples were collected for histological examination. A standard grading system was used to evaluate fracture healing. When the groups were compared in terms of bone healing histopathological scores, a statistically significant difference was observed between group C1 and the other groups (p < 0.005). In the statistical evaluation made according to the histopathological mean scores, the least improvement was observed in group C2. No statistically significant difference was observed between group nHA and group nHA + B1 and group C2 and between group nHA and group nHA + B1 in terms of bone healing scores (p > 0.005). A statistically significant difference was found between group nHA + B2 and group C2 (p = 0.026). Although there was no statistically significant difference in histopathological scores, the mean score closest to group C1 was observed in group nHA + B2. A statistically significant difference was observed between the groups in the scintigraphic evaluation performed on the 28th day of the experimental procedure, and the difference was between group C1 and group nHA + B1 and between group nHA and group nHA + B1 (p = 0.004; p = 0.028, p < 0.005). In the comparison of the values obtained on days 0 and 28 within the group, a statistically significant change was observed in group nHA + B1 and group nHA + B2 (p < 0.005). When the results of the present study were evaluated, it was thought that the boron-doped nHA graft biomaterials may have positive effects on bone healing. Providing a different perspective for the development of an alternative new treatment modality that can be locally applied in the treatment of fractures a serious and common health problem can be interpreted as an important outcome of the present study. We believe that this study will serve as a preliminary study for more comprehensive future studies on this subject.

Simultaneous processing of both handheld biomixing and biowriting of kombucha cultured pre-crosslinked nanocellulose bioink for regeneration of irregular and multi-layered tissue defects

The nanocellulosic pellicle derived from the symbiotic culture of bacteria and yeast (Kombucha SCOBY) is an important biomaterial for 3D bioprinting in tissue engineering. However, this nanocellulosic hydrogel has a highly entangled gel network. This needs to be partially modified to improve its processability and extrusion ability for its applications in the 3D bioprinting area. To control its mechanical and biological properties for direct 3D bioprinting applications, uniform reinforcement of nanocellulose-interacting polymers and nanoparticles in such a prefabricated gel network is essential. In this study, the hydrogel network is partially hydrolyzed with organic acid and subsequently transformed into a 3D bioprintable polyelectrolyte complex with chitosan and kaolin nanoparticles without any chemical crosslinker using a handheld 3D bioprinter. This handheld bioprinter ensures homogeneity in both biomixing and bioprinting of chitosan and kaolin within the modified nanocellulose network for multi-layered bioprinted scaffolds through an extensional shear mechanism. The biomixing simulation, mechanical (static, dynamic, and cyclic), 3D bioprinting, and cellular studies confirm the homogeneous biomixing of kaolin nanoparticles and live cells in this nanocellulose-chitosan polyelectrolyte hydrogel. The combination of SCOBY-derived nanocellulose-chitosan bioink with kaolin nanoparticles and a screw-driven handheld extrusion bioprinter demonstrates a promising platform for layer-by-layer regeneration of complex tissues with homogeneous cell/particle distribution with high cell viability.

Self-Sustained H2O2 and O2 Generation by Calcium Carbonate/Zinc Peroxide Nanocomposite, Enhancing Osteosarcoma Cell Differentiation and Antibacterial Activity

Calcium carbonate nanoparticles (CaCO3 NPs) show promising osteogenic potential due to their ability to release calcium ions and modulate pH. However, their limited bioactivity, potential cytotoxicity, variable degradation rates, poor mechanical properties, and lack of inherent osteoinductivity present significant challenges. In this study, we hypothesized that decorating CaCO3 NPs with another active material, zinc peroxide (ZnO2), can address some of these challenges and enhance the effectiveness of CaCO3 NPs in the treatment of bone cancer and bone regeneration. For this purpose, CaCO3 NPs with the vaterite polymorph were synthesized and decorated with ZnO2 NPs. These nanostructures were thoroughly characterized and thin films with varying layers were fabricated. The CaCO3/ZnO2 films showed greater initial adhesion of osteosarcoma cells (Saos-2 cells) than the CaCO3 films. While CaCO3 NPs promoted cellular proliferation over time, the CaCO3/ZnO2 nanocomposites (NCs) reduced the proliferation of osteosarcoma cells and triggered apoptosis. Analyses of osteogenic markers, including alkaline phosphatase activity, mineralization, and the expression of Runx-2 and osteocalcin, strongly indicated that CaCO3/ZnO2 NCs possess even greater osteogenic potential than CaCO3 NPs alone. The dual effects of CaCO3/ZnO2 on osteosarcoma cells, promoting both osteogenesis and apoptosis, may be attributed to the self-production of H2O2 and O2, along with the controlled release of calcium and zinc ions. Given their osteogenic potential and significant antibacterial activity against Staphylococcus aureus and Escherichia coli, CaCO3/ZnO2 NCs are promising candidates for treating bone tumors and regeneration of bone defects.

Bone regeneration in rabbit cranial defects: 3D printed polylactic acid scaffolds gradually enriched with marine bioderived calcium phosphate

ObjectiveThis study aimed to evaluate the in vivo biocompatibility, mechanical performance and osteoconductive potential of 3D-printed polylactic acid (PLA) scaffolds enriched with marine bioderived calcium phosphate (bioCaP) for bone tissue engineering. Materials and MethodsPLA-bioCaP composite scaffolds were specifically designed for the rabbit cranial defect model by 3D printing, with a uniform distribution of open square-shaped pores and contributions in bioCaP. Physicochemical and mechanical characterization and the evaluation of biological response are presented. ResultsThe scaffolds demonstrated mechanical properties comparable to human bones, integration with the host bone, and osteoconductive behavior promoting cell ingrowth from the defect edge. Strong mineralized tissue ingrowth through the scaffolds’ pores was observed, providing notable support to the host bone. In quantitative terms, micro-CT and histomorphometry analysis post-implantation revealed no significant differences in bone regeneration across all groups. ConclusionThe 3D-printed scaffolds with perpendicular patterning, open porosity, and proposed composition displayed satisfactory mechanical properties, biocompatibility, and osteoconductive response. The scaffolds promoted bone regeneration at similar levels as the PLA. The highest contribution of bioCaP promoted a positive influence in certain histomorphometric parameters; however, it did not significantly improve their osteogenic capability. Further research is required to optimize scaffold composition and enhance their osteogenic potential. Clinical RelevanceThis study presents a significant advancement in bone tissue engineering through the development of personalized composite scaffolds for bone-related applications. The clinical implications of this research are profound, especially considering the increasing demand for functional bone regeneration technologies capable of producing cost-effective producing cost-effective customized scaffolds.

Application of miR-29a-Exosome and Multifunctional Scaffold for Full-Thickness Cartilage Defects

BackgroundFull-thickness cartilage defect is a common refractory disease in orthopedics. In this study, we designed a novel composite scaffold composed of silk fibroin-chitosan for the cartilage layer and porous tantalum for the subchondral bone layer, loaded with engineered bone mesenchymal stem cell exosomes, to evaluate its efficacy in repairing full-thickness cartilage defect. MethodsPorous tantalum was 3D printed and combined with silk fibroin-chitosan to form a composite scaffold. Chondrocytes were cultured on the scaffold, and their growth was assessed using the CCK-8 method. Toluidine blue staining confirmed cell morphology, while immunofluorescence revealed collagen type Ⅱ expression. Engineered exosomes loaded with miR-29a were created and characterized using various techniques. Co-culturing with chondrocytes demonstrated their proliferation over 10 days. Immunofluorescence revealed staining for the nucleus, collagen type II, and Aggrecan. In vivo experiments were performed on rats to assess cartilage defect repair, utilizing histological staining and micro-CT scanning at 4 and 8 weeks post-operation. ResultsThe silk fibroin-chitosan scaffold demonstrated good biocompatibility, supporting chondrocyte adhesion, growth, and cartilage tissue formation. Engineered exosomes exhibited promising biological activity, conducive to bone and cartilage regeneration. The implantation of the silk fibroin-chitosan/porous tantalum composite scaffold loaded with engineered exosomes promoted integration with the surrounding bone and cartilage tissues, facilitating repair and regeneration. ConclusionsThe silk fibroin-chitosan combined with porous tantalum scaffold carrying engineered exosomes loaded with miR-29a has good potential for full-thickness cartilage defects regeneration.

Engineered Osteochondral Scaffolds with Bioactive Cartilage Zone for Enhanced Articular Cartilage Regeneration.

Despite progress, osteochondral (OC) tissue engineering strategies face limitations in terms of articular cartilage layer development and its integration with the underlying bone tissue. The main objective of this study is to develop a zonal OC scaffold with native biochemical signaling in the cartilage zone to promote articular cartilage development devoid of cells and growth factors. Herein, we report the development and in vivo assessment of a novel gradient and zonal-structured scaffold for OC defect regeneration. The scaffold system is composed of a mechanically supportive 3D-printed template containing decellularized cartilage extracellular matrix (ECM) biomaterial in the cartilage zone that possesses bioactive characteristics, such as chemotactic activity and native tissue biochemical composition. OC scaffolds with a bioactive cartilage zone were implanted in vivo in a rabbit osteochondral defect model and assessed for gross morphology, matrix deposition, cellular distribution, and overall tissue regeneration. The scaffold system supported recruitment and infiltration of host cells into the cartilage zone of the graft, which led to increased ECM deposition and physiologically relevant articular cartilage tissue formation. Semi-quantitative ICRS scoring (overall score double for OC scaffold with bioactive cartilage zone compared to PLA scaffold) further confirm the bioactive scaffold enhanced articular cartilage engineering. This strategy of designing bioactive scaffolds to promote endogenous cellular infiltration can be a much simpler and effective approach for OC tissue repair and regeneration.

Inflammation-regulated and nutrient-supplied scaffolds promote bone regeneration in diabetic microenvironment in vivo

The harsh microenvironment of persistent inflammation and insufficient nutrient supply in diabetic organism impedes severely the osteogenic differentiation. Current management on diabetic microenvironment regulation has been focused on glycemic control and eliminating reactive oxygen species (ROS), which is inefficient to modulate the harsh diabetic microenvironment to promote bone regeneration. Herein, a surface-functionalized black phosphorus nanosheets (BPNSs)-coated ROS-scavenging scaffold was designed for the bone healing in type-2 diabetic rats by contributing to nutrient provision, osteogenesis, and anti-inflammation. The BPNSs/tannic acid (TA) were surface coated with cyclodextrin loaded with simvastatin (SIM)/4-carboxy-2-fluorobenzeneboronic acid (FPBA)-grafted hyperbranched poly-l-lysine (HBPL), which were further modified onto the pore walls of poly(lactide-co-glycolide) (PLGA) scaffold. The BPNSs gradually degraded to release phosphate, which served as an important component of bone, and together with the released SIM, synergistically promoted osteogenesis differentiation of MC3T3-E1 cells in a β-glycerophosphate-free medium. The TA and FPBA on the scaffold alleviated the inflammatory environment by ROS depletion and downregulating inflammatory factors, resulting in better bone regeneration in skull defects of diabetic rats in vivo. The remarkable outcomes in vivo verify that the scaffold containing functionalized BPNSs provides an effective strategy for diabetic bone regeneration.

Polyphenols and Functionalized Hydrogels for Osteoporotic Bone Regeneration.

Osteoporosis induces severe oxidative stress and disrupts bone metabolism, complicating the treatment of bone defects. Current therapies often have side effects and require lengthy bone regeneration periods. Hydrogels, known for their flexible mechanical properties and degradability, are promising carriers for drugs and bioactive factors in bone tissue engineering. However, they lack the ability to regulate the local pathological environment of osteoporosis and expedite bone repair. Polyphenols, with antioxidative, anti-inflammatory, and bone metabolism-regulating properties, have emerged as a solution. Combining hydrogels and polyphenols, polyphenol-based hydrogels can regulate local bone metabolism and oxidative stress while providing mechanical support and tissue adhesion, promoting osteoporotic bone regeneration. This review first provides a brief overview of the types of polyphenols and the mechanisms of polyphenols in facilitating adhesion, antioxidant, anti-inflammatory, and bone metabolism modulation in modulating the pathological environment of osteoporosis. Next, this review examines recent advances in hydrogels for the treatment of osteoporotic bone defects, including their use in angiogenesis, oxidative stress modulation, drug delivery, and stem cell therapy. Finally, it highlights the latest research on polyphenol hydrogels in osteoporotic bone defect regeneration. Overall, this review aims to facilitate the clinical application of polyphenol hydrogels for the treatment of osteoporotic bone defects.

Clinical Observations of the Effectiveness of the Masquelet Induced Membrane Technique in the Treatment of Critical Long-Bone Defects of the Lower and Upper Extremities

Background and Objectives: Successful treatment of severe trauma and fractures of the long bones with successful healing and bone union is still a significant challenge for surgeons. Unfortunately, up to 10% of long-bone fractures develop bone healing disorders. The aim of this study was to evaluate the results of treating bone defects with different etiologies in the upper and lower extremities using the induced membrane technique. Materials and Methods: We prospectively evaluated the radiological and clinical outcomes of 45 patients with severe bone defects treated with the induced membrane technique during the period from May 2021 to October 2023. The time to bone defect regeneration, size of the bone defect, and the cost of treatment were evaluated. Functional outcomes were assessed using the Disabilities of the Arm Shoulder and Hand (DASH) scale, SF-36, and the Lower Limb Functional Index (LLFI). Results: The mean follow-up time was 31 months (12–35). There were 20 patients with upper extremity bone defects and 25 with lower extremity bone defects. The mean defect length was 7.9 cm for the upper extremity (3.5–18) and 5.3 cm for the lower extremity (3–11). The mean times to achieve bone union and remodeling were 6.0 months (3–12) and 9 months (3–13) for the upper and lower limbs, respectively. Clinical evaluation at the end of treatment (achieving bone union) showed statistically significant improvements in the DASH, SF-36, and LLFI scales for pre- and postoperative outcomes. There was no statistical significance in the SF-36 clinical scale scores after surgical treatment compared to reconstructive treatment of upper and lower extremity bone defects. Results: The presented reconstructive approach to the treatment of bone defects and healing disorders and extensive analysis demonstrate the effectiveness of the induced membrane technique in a short follow-up period, with a relatively high level of patient comfort and good clinical results in the treatment of severe bone defects with particularly infectious etiologies.

Microenvironment-optimized gastrodin-functionalized scaffolds orchestrate asymmetric division of recruited stem cells in endogenous bone regeneration

The regeneration of osteoporotic bone defects remains challenging as the critical stem cell function is impaired by inflammatory microenvironment. Synthetic materials that intrinsically direct osteo-differentiation versus self-renewal of recruited stem cell represent a promising alternative strategy for endogenous bone formation. Therefore, a microenvironmentally optimized polyurethane (PU) /n-HA scaffold to enable sustained delivery of gastrodin is engineered to study its effect on the osteogenic fate of stem cells. It exhibited interconnected porous networks and an elevated sequential gastrodin release pattern to match immune-osteo cascade concurrent with progressive degradation of materials. In a critical-sized femur defect model of osteoporotic rat, 5% gastrodin-PU/n-HA potently promoted neo-bone regeneration by facilitating M2 macrophage polarization and CD146+ host stem cell recruitment to defective site. The implantation time-dependently increased the bone marrow mesenchymal stem cell (BMSC) population, and further culture of BMSCs showed a robust ability of proliferation, migration, and mitochondrial resurgence. Of note, some of cell pairs produced one stemness daughter cell while the other committed to osteogenic lineage in an asymmetric cell division (ACD) manner, and a much more compelling ACD response was triggered when 5% gastrodin-PU/n-HA implanted. Further investigation revealed that one-sided concentrated presentation of aPKC and β-catenin in dividing cells effectively induced asymmetric distribution, which polarized aPKC biased the response of the daughter cells to Wnt signal. The asymmetric cell division in skeletal stem cells (SSCs) was mechanically comparable to BMSCs and also governed by distinct aPKC and β-catenin biases. Concomitantly, delayed bone loss adjacent to the implant partly alleviated development of osteoporosis. In conclusion, our findings provide insight into the regulation of macrophage polarization combined with osteogenic commitment of recruited stem cells in an ACD manner, advancing scaffold design strategy for endogenous bone regeneration.Graphical abstract

Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration.

Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30-70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ± 1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50-95%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC matrix. The tensile Young's modulus (E), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.

Connective Tissue Graft May Compensate for Residual Bone Defect of the Implant in the Esthetic Zone: A Case Report with 7-year Follow-up

The present case report aimed to demonstrate the case using a connective tissue graft (CTG) to compensate for a residual defect after guided bone regeneration (GBR) in the anterior maxillary area. An extensive number of studies have reported successful outcomes of horizontal bone augmentation, but it was also demonstrated that a complete resolution of the defect may not be achieved in all cases. In the present case report, the patient underwent implant placement simultaneously with GBR at the anterior maxillary area. After 4 months, partial regeneration of the initial defect was observed. To compensate for such residual defect, a CTG was applied. Other expectations by the CTG were to enhance tissue volume and phenotype. The final prosthesis was delivered after 3 months. Up to 7 years, favorable radiographic and clinical situations were observed. In conclusion, a CTG may compensate for residual bone defect of the implant in the esthetic zone.

Framework Nucleic Acid-Based Selective Cell Catcher for Endogenous Stem Cell Recruitment.

Cell-surface engineering holds great promise in boosting endogenous stem cell attraction for tissue regeneration. However, challenges such as cellular internalization of ligand and the dynamic nature of cell membranes often complicate ligand-receptor interactions. The aim of this study is to harness the innovative potential of programmable tetrahedral framework nucleic acid (tFNA) to enable precise, tunable ligand-receptor interactions, thereby improving stem cell recruitment efficiency. This approach involves experimental screening and theoretical analysis using dissipative particle dynamics. The results demonstrate that altering the flexibility and topology of ligands on tFNA changes their cellular internalization and membrane binding efficiency. Furthermore, optimizing the distribution of the mesenchymal stem cell (MSC)-binding aptamer 19S (Apt19S) on the tFNA enhances the stem cell capture efficiency. Following successful in vitro MSC capture, Apt19S-modified tFNA is chemically linked to a hyaluronic acid hydrogel, forming an efficient "stem cell catcher" system. Subsequent in vivo experiments demonstrate that this system effectively promotes early stem cell recruitment and accelerates bone regeneration in different bone healing scenarios, including cranial and maxillary defects.

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.

Effect of nHA/CS/PLGA delivering adipose stem cell-derived exosomes and bone marrow stem cells on bone healing—in vitro and in vivo studies

Adipose stem cell-derived exosomes (ADSC-EXO) have been demonstrated to promote osteogenic differentiation of bone marrow stem cells (BMSCs) and facilitate bone regeneration. The present study aims to investigate the effect of ADSC-EXO-loaded nano-hydroxyapatite/chitosan/poly-lactide-co-glycolide (nHA/CS/PLGA) scaffolds on maxillofacial bone regeneration using tissue engineering. ADSC-EXO was isolated and co-cultured with BMSCs, and the osteogenic differentiation of BMSCs was assessed through the detection of mineralized nodule formation, alkaline phosphatase (ALP) activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). The nHA/CS/PLGA scaffolds were fabricated and loaded with ADSC-EXO and BMSCs, and these tissue engineering complexes were applied to the maxillofacial bone defect region of rabbits to elucidate their bone regeneration effect. The osteogenic differentiation of BMSCs was markedly enhanced when they were co-cultured with ADSC-EXO. This was evidenced by an increase in the formation of mineralized nodule formation, ALP activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). In vivo experiments demonstrated that the application of ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds effectively repaired maxillofacial bone defects in rabbits. ADSC-EXO has been demonstrated to promote the osteogenic differentiation of BMSCs. The ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds have been shown to facilitate the regeneration of maxillofacial bone defects. This may serve as a potential therapeutic strategy for large-scale bone defects.

3D-printed bioactive scaffolds: an emerging strategy for the regeneration of infectious bone defects

3D-printed bioactive scaffolds: an emerging strategy for the regeneration of infectious bone defects

Electron-donable heterojunctions with synergetic Ru-Cu pair sites for biocatalytic microenvironment modulations in inflammatory mandible defects

The clinical treatments of maxillofacial bone defects pose significant challenges due to complex microenvironments, including severe inflammation, high levels of reactive oxygen species (ROS), and potential bacterial infection. Herein, we propose the de novo design of an efficient, versatile, and precise electron-donable heterojunction with synergetic Ru-Cu pair sites (Ru-Cu/EDHJ) for superior biocatalytic regeneration of inflammatory mandible defects and pH-controlled antibacterial therapies. Our studies demonstrate that the unique structure of Ru-Cu/EDHJ enhances the electron density of Ru atoms and optimizes the binding strength of oxygen species, thus improving enzyme-like catalytic performance. Strikingly, this biocompatible Ru-Cu/EDHJ can efficiently switch between ROS scavenging in neutral media and ROS generation in acidic media, thus simultaneously exhibiting superior repair functions and bioadaptive antibacterial properties in treating mandible defects in male mice. We believe synthesizing such biocatalytic heterojunctions with exceptional enzyme-like capabilities will offer a promising pathway for engineering ROS biocatalytic materials to treat trauma, tumors, or infection-caused maxillofacial bone defects.

GelMA-based moldable and rapid-curable osteogenic paste inspired by ceramic craft for alveolar bone defect regeneration

Alveolar bone defects pose a significant challenge in oral clinical treatments, impacting procedures such as dental implants, orthodontics, and oral restoration. Despite their frequent occurrence due to various causes, the effective restoration and reconstruction of alveolar bone defects remain a significant clinical challenge in dentistry. Existing treatments often rely on intrinsic blood coagulation to stabilize bone grafts, but they present limitations such as gradual clotting and reduced effectiveness in patients with coagulation dysfunction. Injectable gel holds promise as an alternative to coagulation-dependent bone graft matrices, but it also faces challenges, including low initial viscosity and dependence on the natural formation of the defect area during the curing process. Here, we present a ceramic-craft-inspired osteogenic (CIO) hydrogel, designed to achieve moldable and curable properties for bone defect regeneration. This injectable paste, composed of gelatin methacrylate (GelMA), nanoclay, and bone grafts, allows for local injection and manual shaping without the need for molds. The shaped hydrogel rapidly crosslinks within 15 s under UV irradiation, providing malleability, strength, and coagulation-independent bone graft stabilization. This approach offers a potential breakthrough in addressing the persistent clinical challenge of alveolar bone defect restoration.

Vertical Alveolar Ridge Regeneration by Means of Periosteal Activation-A Proof-of-Principle Study.

To assess the possibility of vertical alveolar ridge augmentation by means of activation of the periosteum. Six adult male Beagle dogs were used for the study. All premolars and first molars were extracted, and one vertical saucer-shaped bony defect was created on each side of the mandible. After 3 months of healing, full-thickness muco-periosteal flaps were elevated, and one distraction device was placed on each side of the mandible. The distraction plate was left submerged, and the activation mechanism connected to the distraction rod was exposed intra-orally. The protocol of periosteal activation (PP: periosteal 'pumping') was initiated after a latency of 7 days. The alternation of activation and relaxation at the rate of 0.35 mm/12 h during 5 days was followed by the sole activation of 0.35 mm/12 h for 5 days (PP group). Devices were left inactivated on the contralateral control side of the mandible (C group). All animals were euthanized after 8 weeks of consolidation. Samples were analysed histologically and by means of micro-CT. New mature lamellar bone was formed over the pristine bone in all groups. More intensive signs of bone modelling and remodelling were observed in the PP group compared to the C group. Mean new bone, bone marrow, connective tissue and total volumetric densities were greater in the PP group (p < 0.001, p = 0.001, p = 0.003 and p < 0.001, respectively). No differences were observed in the relative area parameters. Total tissue volume and bone volume were higher in the PP group (p = 0.031 and p = 0.076, respectively), while the bone mineral densities were higher in the C group (p = 0.041 and p = 0.003, respectively). Trabecular number, trabecular thickness and trabecular separation values were similar between the two groups. Regeneration of vertical alveolar bone ridge defects may be enhanced by activation of the periosteum, without the application of bone grafting materials.

Recent Advances in Biomaterial‐Based Scaffolds for Guided Bone Tissue Engineering: Challenges and Future Directions

ABSTRACTBone tissue engineering (BTE) has emerged as a promising approach for the regeneration and repair of bone defects caused by trauma, disease, or aging. This review provides an overview of recent advancements in BTE, with a focus on the development and application of biomaterial‐based scaffolds, including natural (e.g., collagen, chitosan), synthetic (e.g., polylactic acid [PLA], polycaprolactone [PCL]), and composite materials (e.g., hydroxyapatite‐based composites). It discusses their properties, benefits, and limitations. Additionally, this review examines innovative fabrication strategies such as 3D printing, electrospinning, and freeze‐drying, which enhance scaffold customization and performance. This review aims to provide insights into future directions of BTE research and its potential applications in regenerative medicine. Functionalization strategies, including surface modifications, coating, and the incorporation of growth factors and cells, are reviewed for their roles in improving scaffold bioactivity. In vivo and in vitro research have demonstrated the therapeutic promise of these scaffolds, while current clinical trials offer insights into their translational use. Challenges facing the translation of these technologies into clinical practice are also highlighted.