Bone Regeneration In Defects Research Articles

Advances in biomaterials for oral-maxillofacial bone regeneration: spotlight on periodontal and alveolar bone strategies.

The intricate nature of oral-maxillofacial structure and function, coupled with the dynamic oral bacterial environment, presents formidable obstacles in addressing the repair and regeneration of oral-maxillofacial bone defects. Numerous characteristics should be noticed in oral-maxillofacial bone repair, such as irregular morphology of bone defects, homeostasis between hosts and microorganisms in the oral cavity and complex periodontal structures that facilitate epithelial ingrowth. Therefore, oral-maxillofacial bone repair necessitates restoration materials that adhere to stringent and specific demands. This review starts with exploring these particular requirements by introducing the particular characteristics of oral-maxillofacial bones and then summarizes the classifications of current bone repair materials in respect of composition and structure. Additionally, we discuss the modifications in current bone repair materials including improving mechanical properties, optimizing surface topography and pore structure and adding bioactive components such as elements, compounds, cells and their derivatives. Ultimately, we organize a range of potential optimization strategies and future perspectives for enhancing oral-maxillofacial bone repair materials, including physical environment manipulation, oral microbial homeostasis modulation, osteo-immune regulation, smart stimuli-responsive strategies and multifaceted approach for poly-pathic treatment, in the hope of providing some insights for researchers in this field. In summary, this review analyzes the complex demands of oral-maxillofacial bone repair, especially for periodontal and alveolar bone, concludes multifaceted strategies for corresponding biomaterials and aims to inspire future research in the pursuit of more effective treatment outcomes.

Polyphenols-based intelligent oral barrier membranes for periodontal bone defect reconstruction

Abstract Periodontitis-induced periodontal bone defects significantly impact patients’ daily lives. The guided tissue regeneration and guided bone regeneration techniques, which are based on barrier membranes, have brought hope for the regeneration of periodontal bone defects. However, traditional barrier membranes lack antimicrobial properties and cannot effectively regulate the complex oxidative stress microenvironment in periodontal bone defect areas, leading to unsatisfactory outcomes in promoting periodontal bone regeneration. To address these issues, our study selected the collagen barrier membrane as the substrate material and synthesized a novel barrier membrane (PO/4-BPBA/Mino@COL, PBMC) with an intelligent antimicrobial coating through a simple layer-by-layer assembly method, incorporating reactive oxygen species (ROS)-scavenging components, commercial dual-functional linkers and antimicrobial building blocks. Experimental results indicated that PBMC exhibited good degradability, hydrophilicity and ROS-responsiveness, allowing for the slow and controlled release of antimicrobial drugs. The outstanding antibacterial, antioxidant and biocompatibility properties of PBMC contributed to resistance to periodontal pathogen infection and regulation of the oxidative balance, while enhancing the migration and osteogenic differentiation of human periodontal ligament stem cells. Finally, using a rat periodontal bone defect model, the therapeutic effect of PBMC in promoting periodontal bone regeneration under infection conditions was confirmed. In summary, the novel barrier membranes designed in this study have significant potential for clinical application and provide a reference for the design of future periodontal regenerative functional materials.

Effect of a synthetic hydroxyapatite-based bone grafting material compared to established bone substitute materials on regeneration of critical-size bone defects in the ovine scapula.

Lately, the potential risk of disease transmission due to the use of bovine-derived bone substitutes has become obvious, demonstrating the urgent need for a synthetic grafting material with comparable bioactive behaviour and properties. Therefore, the effect of a synthetic hydroxyapatite (HA) (Osbone®) bone grafting material on bone regeneration was evaluated 2 weeks, 1 month, and 3, 6, 12 and 18 months after implantation in critical-size bone defects in the ovine scapula and compared to that of a bovine-derived HA (Bio-Oss®) and β-tricalcium phosphate (TCP) (Cerasorb® M). New bone formation and the biodegradability of the bone substitutes were assessed histomorphometrically. Hard tissue histology and immunohistochemical analysis were employed to characterize collagen type I, alkaline phosphatase, osteocalcin, as well as bone sialoprotein expression in the various cell and matrix components of the bone tissue to evaluate the bioactive properties of the bone grafting materials. No inflammatory tissue response was detected with any of the bone substitute materials studied. After 3 and 6 months, β-TCP (Cerasorb® M) showed superior bone formation when compared to both HA-based materials (3 months: β-TCP 55.65 ± 2.03% vs. SHA 49.05 ± 3.84% and BHA 47.59 ± 1.97%; p ≤ 0.03; 6 months: β-TCP 62.03 ± 1.58%; SHA: 55.83 ± 2.59%; BHA: 53.44 ± 0.78%; p ≤ 0.04). Further, after 12 and 18 months, a similar degree of bone formation and bone-particle contact was noted for all three bone substitute materials without any significant differences. The synthetic HA supported new bone formation, osteogenic marker expression, matrix mineralization and good bone-bonding behaviour to an equal and even slightly superior degree compared to the bovine-derived HA. As a result, synthetic HA can be regarded as a valuable alternative to the bovine-derived HA without the potential risk of disease transmission.

A NEW TISSUE-ENGINEERED PRODUCT INDICATED FOR BONE RECONSTRUCTION: PROOF OF CONCEPT

To design slow resorption patient-specific bone graft whose properties of bone regeneration are increased by its geometry and composition and to assess it in in-vitro and in-vivo models.A graft composed by hydroxyapatite (HA) and β-TCP was designed as a cylinder with 3D gyroid porosities and 7 mm medullary space based on swine's anatomy. It was produced using a stereolithography 3D-printing machine (V6000, Prodways).Sterile bone grafts impregnated with or without a 10µg/mL porcine BMP-2 (pBMP-2) solution were implanted into porcine femurs in a bone loss model. Bone defect was bi-weekly evaluated by X-ray during 3 months. After sacrifice, microscanner and non-decalcified histology analysis were conducted on biopsies.Finally, osteoblasts were cultured inside the bone graft or in monolayer underneath the bone graft. Cell viability, proliferation, and gene expression were assessed after 7 and 14 days of cell culture (n=3 patients).3D scaffolds were successfully manufactured with a composition of 80% HA and 20% β-TCP ±5% with indentation compressive strength of 4.14 MPa and bending strength of 11.8MPa.In vivo study showed that bone regeneration was highly improved in presence of pBMP-2. Micro-CT shows a filling of the gyroid sinuses of the implant (Figure 1).In vitro, the presence of BMP2 did not influence the viability of the osteoblasts and the mortality remained below 3%. After 7 days, the presence of BMP2 in the scaffold significantly increased by 85 and 65% the COL1A1 expression and by 8 and 33-fold the TNAP expression by osteoblasts in the monolayer or in the scaffold, respectively. This BMP2 effect was transient in monolayer and did not modify gene expression at day 14.BMP2-impregnated bone graft is a promising patient-personalized 3D-printed solution for bone defect regeneration, by promoting neighboring host cells recruitment and solid new bone formation.For any figures and tables, please contact the authors directly.

A coaxial electrospun mat coupled with piezoelectric stimulation and atorvastatin for rapid vascularized bone regeneration.

The repair of critical bone defects caused by various clinical conditions needs to be addressed urgently, and the regeneration of large bone defects depends on early vascularization. Therefore, enhanced vascularization of artificial bone grafts may be a promising strategy for the regeneration of critical-sized bone defects. Taking into account the importance of rapid angiogenesis during bone repair and the potential of piezoelectric stimulation in promoting bone regeneration, novel coaxial electrospun mats coupled with piezoelectric materials and angiogenic drugs were fabricated in this study using coaxial electrospinning technology, with a shell layer loaded with atorvastatin (AVT) and a core layer loaded with zinc oxide (ZnO). AVT was used as an angiogenesis inducer, and piezoelectric stimulation generated by the zinc oxide was used as an osteogenesis enhancer. The multifunctional mats were characterized in terms of morphology, core-shell structure, piezoelectric properties, drug release, and mechanical properties, and their osteogenic and angiogenic capabilities were validated in vivo and ex vivo. The results revealed that the coaxial electrospun mats exhibit a porous surface morphology and nanofibers with a core-shell structure, and the piezoelectricity of the mats improved with increasing ZnO content. Excellent biocompatibility, hydrophilicity and cell adhesion were observed in the multifunctional mats. Early and rapid release of AVT in the fibrous shell layer of the mat promoted angiogenesis in human umbilical vascular endothelial cells (HUVECs), whereas ZnO in the fibrous core layer harvested bioenergy and converted it into electrical energy to enhance osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs), and both modalities synergistically promoted osteogenesis and angiogenesis. Furthermore, optimal bone regeneration was achieved in a model of critical bone defects in the rat mandible. This osteogenesis-promoting effect was induced by electrical stimulation via activation of the calcium signaling pathway. This multifunctional mat coupling piezoelectric stimulation and atorvastatin promotes angiogenesis and bone regeneration, and shows great potential in the treatment of large bone defects.

Static magnetic field enhances the bone remodelling capacity of human demineralized bone matrix in a rat animal model of cranial bone defects.

The regeneration of bone defects that exceed 2 cm is a challenge for the human body, necessitating interventional therapies. Demineralized bone matrices (DBM) derived from biological tissues have been employed for bone regeneration and possess notable osteoinductive and osteoconductive characteristics. Nevertheless, their efficiency in regenerating critically sized injuries is limited, and therefore additional signaling cues are required. Thanks to the piezoelectric properties of the bone, external physical stimulation is shown to accelerate tissue healing. We have implanted human DBM in critically sized cranial bone defects in rat animal models and exposed them to an external magnetic field (1 T) to enhance endogenous bone formation. Our in vitro experiments showed the superior cytocompatibility of DBM compared to cell culture plates. Furthermore, alkaline phosphatase activity after 14 days and Alizarin red staining at 28 days demonstrated differentiation of rat bone marrow mesenchymal stem cells into bone lineage on DBM. Computer tomography images together with histological analyses showed that implanting DBM in the injured rats significantly enhanced bone regeneration. Notably, combining DBM transplantation with a 2 h daily exposure to a 1 T magnetic field for 2 weeks (day 7 to 21 post-surgery) significantly improved bone regeneration compared to DBM transplantation alone. This research indicates that utilizing external magnetic stimulation significantly enhances the potential of bone allografts to regenerate critically sized bone defects.

Structure-optimized and microenvironment-inspired nanocomposite biomaterials in bone tissue engineering

Abstract Critical-sized bone defects represent a significant clinical challenge due to their inability to undergo spontaneous regeneration, necessitating graft interventions for effective treatment. The development of tissue-engineered scaffolds and regenerative medicine has made bone tissue engineering a highly viable treatment for bone defects. The physical and biological properties of nanocomposite biomaterials, which have optimized structures and the ability to simulate the regenerative microenvironment of bone, are promising for application in the field of tissue engineering. These biomaterials offer distinct advantages over traditional materials by facilitating cellular adhesion and proliferation, maintaining excellent osteoconductivity and biocompatibility, enabling precise control of degradation rates, and enhancing mechanical properties. Importantly, they can simulate the natural structure of bone tissue, including the specific microenvironment, which is crucial for promoting the repair and regeneration of bone defects. This manuscript provides a comprehensive review of the recent research developments and applications of structure-optimized and microenvironment-inspired nanocomposite biomaterials in bone tissue engineering. This review focuses on the properties and advantages these materials offer for bone repair and tissue regeneration, summarizing the latest progress in the application of nanocomposite biomaterials for bone tissue engineering and highlighting the challenges and future perspectives in the field. Through this analysis, the paper aims to underscore the promising potential of nanocomposite biomaterials in bone tissue engineering, contributing to the informed design and strategic planning of next-generation biomaterials for regenerative medicine.

A MODERN VIEW ON REPARATIVE OSTEOGENESIS: MAIN STAGES AND THEIR PATTERNS

Introduction. Reparative osteogenesis is a staged mechanism that ensures the restoration of damaged bone tissue. The study and summarization of current data about bone defect regeneration is the basis for the search and development of methods to improve this process. The aim of the study is to analyze and systematize the current data about reparative osteogenesis, describe the main stages and their patterns. Materials and methods. Searching the relevant sources using online scientific databases and keywords. Selection of publications for review. Further analysis and synthesis of information. The results. Despite different interpretations of the stages of reparative osteogenesis by researchers, they all describe the same coordinated process. The following key stages have been identified: haematoma formation, inflammation, MSC involvement and angiogenesis, cartilage, connective and bone tissue formation, their subsequent reorganisation, ossification and remodelling. Each of these stages involves specific cellular elements, local and general regulatory factors. The development of osteogenic cells and mechanisms of intercellular interaction, as well as the main signalling pathways and molecules (Wnt, RANK/RANKL/OPG, BMPs, HIF, etc.) that regulate osteo- and angiogenesis are described. The role of hypoxia in the process of bone regeneration and angiogenesis is highlighted. The H-type vessels and their participation in the regulation of osteogenesis are considered. Attention is paid to the phenomenon of ‘chondrocyte transdifferentiation’, which is one of the sources of osteoblasts during endochondral ossification. In the context of remodelling, the law of bone biomechanics and piezoelectric adaptive remodelling, as well as bone multicellular units as microsystems that ensure the restructuring of coarse fibrous bone tissue into lamellar bone tissue, are described. Conclusions. Reparative osteogenesis is a complicated and coordinated process at both the cellular and molecular levels. The regeneration process depends on numerous local and systemic factors and the optimization search is carried out at each stage

Self-assembled peptide hydrogel loaded with functional peptide Dentonin accelerates vascularized bone tissue regeneration in critical-size bone defects.

Regeneration of oral craniofacial bone defects is a complex process, and reconstruction of large bone defects without the use of exogenous cells or bioactive substances remains a major challenge. Hydrogels are highly hydrophilic polymer networks with the potential to promote bone tissue regeneration. In this study, functional peptide Dentonin was loaded onto self-assembled peptide hydrogels (RAD) to constitute functionally self-assembling peptide RAD/Dentonin hydrogel scaffolds with a view that RAD/Dentonin hydrogel could facilitate vascularized bone regeneration in critical-size calvarial defects. The functionalized peptide RAD/Dentonin forms highly ordered β-sheet supramolecular structures via non-covalent interactions like hydrogen bonding, ultimately assembling into nano-fiber network. RAD/Dentonin hydrogels exhibited desirable porosity and swelling properties, and appropriate biodegradability. RAD/Dentonin hydrogel supported the adhesion, proliferation and three-dimensional migration of bone marrow mesenchymal stem cells (BMSCs) and has the potential to induce differentiation of BMSCs towards osteogenesis through activation of the Wnt/β-catenin pathway. Moreover, RAD/Dentonin hydrogel modulated paracrine secretion of BMSCs and increased the migration, tube formation and angiogenic gene expression of human umbilical vein endothelial cells (HUVECs), which boosted the angiogenic capacity of HUVECs. In vivo, RAD/Dentonin hydrogel significantly strengthened vascularized bone formation in rat calvarial defect. Taken together, these results indicated that the functionalized self-assembling peptide RAD/Dentonin hydrogel effectively enhance osteogenic differentiation of BMSCs, indirectly induce angiogenic effects in HUVECs, and facilitate vascularized bone regeneration in vivo. Thus, it is a promising bioactive material for oral and maxillofacial regeneration.

Bioinspired triple-layered membranes for periodontal guided bone regeneration applications.

Barrier membranes have been used for the treatment of alveolar bone loss caused by periodontal diseases or trauma. However, an optimal barrier membrane must satisfy multiple requirements simultaneously, which are challenging to combine into a single material. We herein report the design of a bioinspired membrane consisting of three functional layers. The primary layer is composed of clay nanosheets and chitin, which form a nacre-inspired laminated structure. A calcium phosphate mineral layer is deposited on the inner surface of the nacre-inspired layer, while a poly(lactic acid) layer is coated on the outer surface. The composite membrane integrates good mechanical strength and deformability because of the nacre-inspired structure, facilitating operations during the implant surgery. The mineral layer induces the osteogenic differentiation of bone marrow mesenchymal stem cells and increases the stiffness of the membrane, which is an important factor for the regeneration process. The poly(lactic acid) layer can prevent unwanted mineralization on the outer surface of the membrane in oral environments. Cell experiments reveal that the membrane exhibits good biocompatibility and anti-infiltration capability toward connective tissue/epithelium cells. Furthermore, in vitro analyses show that the membrane does not degrade too fast, allowing enough time for bone regeneration. In vivo experiments prove that the membrane can effectively induce better bone regeneration and higher trabecular bone density in alveolar bone defects. This study demonstrates the potential of this bioinspired triple-layered membrane with hierarchical structures as a promising barrier material for periodontal guided tissue regeneration.

A bioswitchable siRNA delivery system: RNAi therapy based on tetrahedral framework nucleic acids for bone defect repair.

Craniofacial bone defects, caused by trauma, congenital abnormalities, or various diseases, present a significant challenge in regenerative medicine. One approach to addressing this problem is the use of RNA interference (RNAi) technology with small interfering RNA (siRNA). CKIP-1 is a negative regulatory molecule for bone formation. However, direct applications of CKIP-1 siRNA for bone defects are still limited. The instability and poor cellular uptake ability of CKIP-1 siRNA restrict its clinical applications. A new drug delivery system is critically needed to enhance the effectiveness and potential applications of CKIP-1 siRNA. Tetrahedral framework nucleic acid (tFNA) is a promising drug delivery system due to its stability and transport abilities. In this study, we developed a bioswitchable siRNA delivery system (BiRDS) based on tFNA to carry CKIP-1 siRNA and examined its effect on bone defect repair. siRNA was successfully loaded into the tFNA core, forming BiRDS, which improved siRNA stability and cellular uptake. After entering cells, BiRDS exposed siRNA, enhancing CKIP-1 silencing efficiency. This system significantly promoted osteogenic differentiation and bone regeneration in rat mandibular bone defects, offering a new strategy for bone regeneration therapy.

Evaluation of post-extraction alveolar regeneration time in advanced periodontal disease employing novel hydroxyapatitepolymeric (FlexiOss®Vet) in dogs.

The purpose of the study was to demonstrate bone regeneration and the time of formation of new alveolar bone based on implanted FlexiOss®Vet bone substitute material. The study attempted to determine the time taken to fill bone defects with newly formed osseous bone compared to alveoli with a standard method of filling the post-extraction alveolus with a collagen sponge. The study was conducted on a group of 12 dogs with advanced periodontal disease (stage IV) in which polymeric hydroxyapatite bone substitute material (FlexiOss®Vet) was implanted into alveoli on the right side, and collagen sponge was implanted into alveoli on the left side in the same patient. The patients underwent macroscopic inspection and X-ray examination at different periods of regeneration after the procedure. On the right side, macroscopically, the alveoli showed features of marked enlargement, and on X-ray examination they gave opacity to X-rays and there was no clear border between the alveolus and alveolar bone. On the left side, the alveoli were clearly penetrable to X-rays, and hollow alveoli filled mainly with connective tissue were observed. The study also showed a significant reduction in bone healing time in alveoli with implants compared to self-healing alveoli. These results suggest that the implanted material is significantly beneficial in the process of bone regeneration in large bone defects in dogs and notably shortens the process of bone regeneration after tooth extractions. It is presumed that this could reflect a model for the treatment of large bone defects in not only the maxilla and mandible, but also long bones, and that it could be a model for alveolar healing in humans.

Oral mesenchymal cells, a specific niche, from development to regeneration

Oral buccal tissues, including bone and mucosa, have unique properties. Oral mucosal fibroblasts and jaw osteoblasts, both derived from Cranial Neural Crest cells, play a key role in healing and repair. These cells express a specific repertoire of genes with their regenerative properties, but also craniofacial diseases. Understanding these tissues holds clinical promise for tissue regeneration and repair of bone and mucosal defects. These multidisciplinary advances also offer potential for better management of periodontal-related conditions and improved oral health.

An Overview of Publications on Extracellular Vesicles in Osteoarthritis from 2012 to 2022: A Bibliometric Analysis

Background. Extracellular vesicles, particularly those derived from stem cells, have demonstrated promising potential in osteoarthritis in recent years. However, there has been no bibliometric analysis focusing on the relationship between extracellular vesicles and osteoarthritis. This study aimed to investigate trends and hotpots of publications on extracellular vesicles in osteoarthritis. Methods. This study collected publications on extracellular vesicles in osteoarthritis from the Web of Science Core Collection database, focusing on English‐language articles and reviews. Quantitative and visual analysis was performed using Microsoft Excel, R shiny, SCImago Graphica, VOS Viewer, and CiteSpace. The data set comprised information on keywords, authors, institutions, journals, and the country or region of the included literature. Journal impact factors and H‐index values were obtained from the 2021 Journal Citation Reports and SJR‐International Science Ranking. Furthermore, we conducted a frequency analysis of annual publications number and fitting curves of the growth trends in the publications. Moreover, we conducted a citation burst analysis of the top 20 keywords and a related bibliometric analysis (word frequency analysis and cocitation analysis) using CiteSpace. Results. A total of 715 documents were analyzed. The number of publications increased annually from 2012 to 2022. China had the highest number (n = 394, 55.1%) of publications and total citations during the decade, followed by the United States (n = 105, 14.7%). Shanghai JiaoTong University contributed the highest number of publications (n = 28, 3.9%). Wang Y has the highest number of publications (n = 40, 5.6%), and Stem Cell Research & Therapy is the journal with the highest number of publications (n = 64, 9.0%). The hotspots of extracellular vesicle research in recent years are umbilical cord blood, drug delivery, and scaffolds. Conclusion. Our findings indicate an increase in publications on the topic in utilizing extracellular vesicles in the context of osteoarthritis. Extracellular vesicle therapy for cartilage regeneration and repair of bone defects in osteoarthritis holds significant potential. Future research will focus on the development of novel drug delivery systems that utilize extracellular vesicles, the creation of novel biomaterials that incorporate extracellular vesicles, and the potential of extracellular vesicles as early diagnostic markers of disease.

A bilayer hydrogel mimicking the periosteum-bone structure for innervated bone regeneration.

In bone tissue, nerves are primarily located in the periosteum and play an indispensable role in bone defect repair. However, most bone tissue engineering approaches ignored the reconstruction of the nerve network. Herein, we aimed to develop a bilayer hydrogel simulating periosteum-bone structure to induce innervated bone regeneration. The bottom "bone" layer consisted of gelatin methacryloyl (GelMA), poly(ethylene glycol) diacrylate (PEGDA), and nano-hydroxyapatite (nHA), whereas the upper "periosteum" layer consisted of GelMA, sodium alginate (SA) and MgCl2. The mechanical properties of the upper and bottom hydrogels were designed to be suitable for neurogenesis and osteogenesis, respectively. Besides, Mg2+ from the "periosteum" layer released at the early stage (within 7 d), which aligned with the optimal time window for nerve regeneration and osteogenic related neuropeptide release. Simultaneously, the prevention of long-term Mg2+ release (after 7 d) could avoid osteogenic inhibition caused by prolonged Mg2+ exposure. Additionally, the incorporation of nHA in the bottom "bone" layer supported the long-term osteogenesis due to its osteoconductivity and slow degradation. In vitro biological experiments revealed that the bilayer hydrogel (GS@Mg/GP@nHA) promoted neurite growth and calcitonin gene-related peptide (CGRP) expression in rat dorsal root ganglion (DRG) neurons, as well as the osteogenesis of rat bone-derived mesenchymal stem cells (BMSCs). Moreover, the in vivo experiments demonstrated that the GS@Mg/GP@nHA hydrogel efficiently promoted nerve network reconstruction and bone regeneration of rat calvarial bone defects. Altogether, the bilayer hydrogel GS@Mg/GP@nHA could promote innervated bone regeneration, providing new insights for biomaterial design for bone tissue engineering.

Применение секретома мультипотентных мезенхимальных стромальных клеток для стимуляции регенерации костной ткани в эксперименте

The article is devoted to a pressing issue in regenerative medicine about the use of cellular products to stimulate reparative regeneration of bone defects. The article presents the results of a study of the structural characteristics of the regenerated rat femoral diaphysis with an induced defect using the secretome of multipotent mesenchymal stromal cells. White outbred rats (males, 120 g) were taken as the object of the study. The study material included femur samples taken on the 7th, 14th, 30th, 60th, 90th and 120th days. The work used methods of computed tomography, anatomical dissection and light microscopy. It has been shown that the use of the secretome of multipotent mesenchymal stromal cells in the early stages activates angiogenesis in the healing area. Against this background, stimulation of reparative osteogenesis occurs with better consolidation of the regenerate with the edges of the defect. In this case, the structure of the regenerate corresponds typical structure of the diaphysis: external and internal systems of bone plates and an osteon layer are observed. All this may indicate earlier remodeling of the regenerate, as well as restoration of the structural and functional characteristics of the bone. The data obtained can be used for further fundamental research in the field of regenerative medicine, as well as in clinical practice.

Small intestine submucosa decorated 3D printed scaffold accelerated diabetic bone regeneration by ameliorating the microenvironment.

The 3D printed scaffolds constructed from polymers have shown significant potential in the field of bone defect regeneration. However, the efficacy of these scaffolds can be markedly reduced in certain pathological conditions like diabetes, where an altered inflammatory microenvironment and diminished small blood vessels complicate the integration of these polymers with the host tissue. In this study, the bioactivity of a 3D-printed poly(lactide-co-glycolide) (PLGA) scaffold is enhanced through the integration of hydroxyapatite (HA), icariin (ICA), and small intestine submucosa (SIS), a form of decellularized extracellular matrix (dECM). The decoration of SIS on the 3D-printed PLGA/HA/ICA scaffold not only improves the mechanical and degradative performance, but also extends the release of ICA from the scaffold. Both in vitro and in vivo studies demonstrate that this functionalized scaffold mitigates the persistent inflammatory conditions characteristic of diabetic bone defects through inducing macrophages towards the M2 phenotype. Additionally, the scaffold promotes angiogenesis by enhancing the migration and tube formation of vascular cells. Furthermore, the synergistic effects of ICA and SIS with the HA scaffolds contribute to the superior osteogenic induction capabilities. This functionalization approach holds significant promise in advancing the treatment of bone defects within the diabetic population, paving a step forward in the application of polymer-based 3D printing technologies in regenerative medicine.

Simulation of the bone remodelling microenvironment by calcium compound-loaded hydrogel fibrous membranes for in situ bone regeneration.

The endowment of guided bone regeneration (GBR) membranes with the ability to activate the endogenous regenerative capability of bone to regenerate bone defects is of clinical significance. Herein we explored the preparation of the calcium compound (CC) (calcium sulfate (CaSL), calcium hydrophosphate (CaHP), or tricalcium phosphate (TCaP)) loaded ultrathin silk fibroin (SF)/gelatin (G) fibre membranes via electrospinning as the GBR membranes to regenerate the calvarial bone defects. The in vitro experiments demonstrated that the CaSL-loaded ultrathin fibrous membranes could simulate optimally the bone remodelling microenvironment in comparison with the CaHP- and TCaP-loaded fibrous membranes, displaying the highest activity to regulate the migration, proliferation, and differentiation of mesenchymal stem cells (MSCs). Also, the in vivo experiments demonstrated that the CaSL-loaded fibrous membranes presented the highest intrinsic osteoinduction to guide in situ regeneration of bone. Furthermore, the in vivo experiments demonstrated that the as-prepared composite fibrous membranes possessed good degradability. In summary, our results suggested that the CaSL-loaded fibrous membranes with high intrinsic osteoinduction and good degradability have potential to translate into clinical practice.

Bone tissue regeneration by 58S bioactive glass scaffolds containing exosome: an in vivo study.

Exosomes, the naturally secreted nanocarriers of cells, have recently been demonstrated to have therapeutic benefits in a variety of disease models where parent cells are not present. However, the use of exosomes in bone defect regeneration has been unusual, and little is documented about the underlying processes. In recent study we produced and characterized exosomes derived human endometrial mesenchymal stem stromal cells and 58S bioactive glass scaffolds; in following, in this research exosome loaded scaffolds synthetized and release of exosome, porosity and bioactivity of them were assessed. More over the effect of scaffolds on repair of critical-size bone defects in rat's calvaria was evaluated by histological examination and micro computed tomography (µ CT). The findings confirmed that constructed porous scaffolds consistently release exosomes; additionally, in vivo findings including Hematoxilin & Eosin staining, Immunohistochemistry, Masson's trichrome, histomorphometric analysis, and µ CT clarified that our implant has osteogenic properties. We discovered that Exo-treated scaffolds might promote osteogenesis especially compared to pure scaffolds, indicating that produced scaffolds containing exosomes could be a potential replacement in bone tissue engineering.

Bioactive layered double hydroxide nanoparticles loaded calcein under GelMA scaffolds promoted osteogenesis and angiogenesis for bone regeneration

In regenerative medicine and tissue engineering, the repair and replacement of damaged or lost bone tissue remains an enduring challenge. Traditional approaches often fail to achieve desired outcomes, but recent advancements in material science have introduced innovative solutions to this issue. Gelatin methacryloyl (GelMA), which is derived from gelatin, has a unique combination of biocompatibility and tunable physical properties for bone tissue engineering applications. In this study, a novel composite was constructed to combine the characteristics of GelMA and bioactive layered double hydroxide (LDH) loaded calcein. The GelMA-LDH-calcein (GLC) scaffold is designed to promote the osteogenic differentiation of mesenchymal stem cells (MSCs) and provide a microenvironment conducive to osteogenic differentiation, ultimately increasing the osteogenic activity to support bone regeneration. Our data demonstrated that GLC promoted the osteogenic differentiation related gene (ALP, Runx2, and OPG) expression in bone marrow-derived MSCs (BMSCs) and angiogenesis of human vascular epithelial cells (HUVECs), making it particularly valuable in the application of bone regeneration in vivo. Through the design, synthesis, and optimization of GLC composites, the optimized scaffolds can provide structure supporting and biological activity for cell proliferation, which promoted bone defect regeneration and could be used for further clinical applications.