Repair calvarial defect of osteoporotic rats by berberine functionalized porous calcium phosphate scaffold.
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ABSTRACT:
SUBMITTER: Wang D
PROVIDER: S-EPMC8240619 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Bone defects, a common orthopedic problem in clinical practice, are a serious threat to human health. As alternative materials to autologous bone grafts, synthetic cell-free functionalized scaffolds have been the focus of recent research in designing scaffolds for bone tissue engineering. Butyryl chitin (BC) is a derivative of chitin (CT) with improved solubility. It has good biocompatibility, but few studies have investigated its use in bone repair. In this study, BC was successfully synthesized with a degree of substitution of 2.1. BC films were prepared using the cast film method and showed strong tensile strength (47.8 ± 4.54 N) and hydrophobicity (86.4 ± 2.46°), which was favorable for mineral deposition. An in vitro cytological assay confirmed the excellent cell attachment and cytocompatibility of the BC film; meanwhile, in vivo degradation indicated the good biocompatibility of BC. Hydroxyapatite (HA), extracted from bovine cancellous bone, had good cytocompatibility and osteogenic induction activity for the mouse osteoblast cell line MC3T3-E1. With the aim of combining the advantages of BC and HA, a BC-HA composite scaffold, with a good pore structure and mechanical strength, was prepared by physical mixing. Administered into skull defects of rats, the scaffolds showed perfect bone-binding performance and effective structural support, and significantly promoted the regeneration of new bone. These results prove that the BC-HA porous scaffold is a successful bone tissue engineering scaffold and has strong potential to be further developed as a substitute for bone transplantation.
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Project description:In this article, we proposed a facile protocol to functionalize porous calcium phosphate ceramics (PCPC) using dietary tea polyphenols (TP). TP molecules was attracted and anchored by Ca2+ ions from the surface of CPC. These TP molecules modulated the nucleation and crystallization of calcium phosphate nanorods assemblies on the surface of PCPC. Our results prove that these calcium phosphate nanorods assemblies accompanies functional groups of TP make PCPC/TP effectively promote proliferation and differentiation of bone mesenchymal stem cells (BMSCs). We inferred that these calcium phosphate nanorods assemblies might change the surface microenvironment of PCPC, which is critical to promote the proliferation and differentiation of BMSCs. Compared with naked PCPC, PCPC/TP obviously increased BMP2, ErK/MAPK and JNK/MAPK level and mineralization capacity of cells (ALP level).
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Project description:Tissue engineering is a promising strategy for bone tissue defect reconstruction. Immunogenic reaction, which was induced by scaffolds degradation or contaminating microorganism, influence cellular activity, compromise the efficiency of tissue engineering, or eventually lead to the failure of regeneration. Inhibiting excessive immune response through modulating scaffold is critical important to promote tissue regeneration. Our previous study showed that ε-poly-L-lysine (EPL)-coated nanoscale polycaprolactone/hydroxyapatite (EPL/PCL/HA) composite scaffold has enhanced antibacterial and osteogenic properties in vitro. However, the bone defect repair function and immunogenic reaction of EPL/PCL/HA scaffolds in vivo remains unclear. In the present study, three nanoscale scaffolds (EPL/PCL/HA, PCL and PCL/HA) were transplanted into rabbit paraspinal muscle pouches, and T helper type 1 (Th1), T helper type 2 (Th2), T helper type 17 (Th17), and macrophage infiltration were analyzed after 1 week and 2 weeks to detect their immunogenic reaction. Then, the different scaffolds were transplanted into rabbit calvarial bone defect to compare the bone defect repair capacities. The results showed that EPL/PCL/HA composite scaffolds decreased pro-inflammatory Th1, Th17, and type I macrophage infiltration from 1 to 2 weeks, and increased anti-inflammatory Th2 infiltration into the regenerated area at 2 weeks in vivo, when compared to PCL and PCL/HA. In addition, EPL/PCL/HA showed an enhanced bone repair capacity compared to PCL and PCL/HA when transplanted into rabbit calvarial bone defects at both 4 and 8 weeks. Hence, our results suggest that EPL could regulate the immunogenic reaction and promote bone defect repair function of PCL/HA, which is a promising agent for tissue engineering scaffold modulation.
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Project description:Currently, the repair of large bone defects still faces numerous challenges, with the most crucial being the lack of large bone grafts with good osteogenic properties. In this study, a novel bone repair implant (degradable porous zinc scaffold/BF Exo composite implant) was developed by utilizing laser melting rapid prototyping 3D printing technology to fabricate a porous zinc scaffold, combining it under vacuum conditions with highly bioactive serum exosomes (BF EXO) and Poloxamer 407 thermosensitive hydrogel. The electron microscope revealed the presence of tea saucer-shaped exosomes with a double-layered membrane structure, ranging in diameter from 30-150 nm, with an average size of 86.3 nm and a concentration of 3.28E+09 particles/mL. In vitro experiments demonstrated that the zinc scaffold displayed no significant cytotoxicity, and loading exosomes enhanced the zinc scaffold's ability to promote osteogenic cell activity while inhibiting osteoclast activity. In vivo experiments on rabbits indicated that the hepatic and renal toxicity of the zinc scaffold decreased over time, and the loading of exosomes alleviated the hepatic and renal toxic effects of the zinc scaffold. Throughout various stages of repairing radial bone defects in rabbits, loading exosomes reinforced the zinc scaffold's capacity to enhance osteogenic cell activity, suppress osteoclast activity, and promote angiogenesis. This effect may be attributed to BF Exo's regulation of p38/STAT1 signaling. This study signifies that the combined treatment of degradable porous zinc scaffolds and BF Exo is an effective and biocompatible strategy for bone defect repair therapy.
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Project description:Osteoporotic fractures are prevalent in society, and their incidence appears to be increasing as the worldwide population ages. However, conventional bone repair materials hardly satisfy the requirements for the repair of pathological fractures. Here, we developed a biomimetic polyetherketoneketone scaffold with a functionalized strontium-doped nanohydroxyapatite coating for osteoporotic bone defect applications. The scaffold has a hierarchically porous architecture and mechanical strength similar to that of osteoporotic trabecular bone. In vitro and in vivo studies demonstrated that the scaffold could promote osteoporotic bone regeneration and delay adjacent bone loss via regulating both osteoblasts and osteoclasts. In addition, the correlations between multiple preimplantation and postimplantation parameters were evaluated to determine the potential predictors of in vivo performance of the material. The current work not only develops a promising candidate for osteoporotic bone repair but also provides a viable approach for designing other functional biomaterials and predicting their translational value.
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Project description:Background: Grafting of biomaterial in alveolar defect facilitates bone healing and orthodontic treatment. BMP2-functionalized biomimetic calcium phosphate (BioCaP) graft had shown excellent bone defect healing potential in many preclinical studies. In this study, we aimed to investigate the influence of BioCaP graft on surgical alveolar bone defect healing during orthodontic tooth movement (OTM) in beagle dogs. Methods: Nine Beagle dogs were randomly assigned to three groups: control, deproteinized bovine bone (DBB), and BioCaP. The maxillary second premolars were protracted into the defects of the extracted maxillary first premolar for 8 weeks. The rate of OTM, alveolar remodeling and bone defect healing were evaluated by histology, histomorphometry, and cone beam computed tomography (CBCT) imaging. Periodontal probing depth was analyzed. Gingival cervicular fluid was collected at week 4 and 8, and the IL-1? level was measured by ELISA. Results: The histological sections of the bone defect showed more newly formed bone in the BioCaP group. The percentage of new bone formation in the BioCaP group was 1.61-, and 1.25-fold higher compared to the control and DBB group, respectively. After 8 weeks of OTM, the resorption rate of BioCaP was 1.42-fold higher compared to DBB. The root resorption index in the DBB group was 1.87-, and 1.39-fold higher compared to the control and BioCaP group, respectively. CBCT images showed 1.92-, and 1.36-fold higher bone mineral density in the BioCaP group compared to the control and DBB group, respectively. There was no significant difference in OTM among the three groups. The distance between the enamel cementum and the crest of the alveolar ridge in the control group was 1.45-, and 1.69-fold higher compared to DBB and BioCaP group, respectively. Periodontal probing depth at week 8 was reduced in the BioCaP group compared to the control. IL-1? concentration in the gingival cervicular fluid was significantly lower in the BioCaP group compared to the control group at week 4 and 8. Conclusion: BioCaP graft robustly promoted bone regeneration and alveolar bone defect healing without affecting OTM. BioCaP graft caused less alveolar bone recession and root resorption of traction tooth with favorable periodontal attachment level indicating that BioCaP as a bioactive and functional bone filling material for alveolar bone defects during orthodontic treatment.
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Project description:Self-fitting scaffolds prepared from biodegradable poly(ε-caprolactone)-diacrylate (PCL-DA) have been developed for the treatment of craniomaxillofacial (CMF) bone defects. As a thermoresponsive shape memory polymer (SMP), with the mere exposure to warm saline, these porous scaffolds achieve a conformal fit in defects. This behavior was expected to be advantageous to osseointegration and thus bone healing. Herein, for an initial assessment of their regenerative potential, a pilot in vivo study was performed using a rabbit calvarial defect model. Exogenous growth factors and cells were excluded from the scaffolds. Key scaffold material properties were confirmed to be maintained following gamma sterilization. To assess scaffold integration and neotissue infiltration along the defect perimeter, non-critically sized (d = 8 mm) bilateral calvarial defects were created in 12 New Zealand white rabbits. Bone formation was assessed at 4 and 16 weeks using histological analysis and micro-CT, comparing defects treated with an SMP scaffold (d = 9 mm x t = 1 or 2 mm) to untreated defects (i.e. defects able to heal without intervention). To further assess osseointegration, push-out tests were performed at 16 weeks and compared to defects treated with poly(ether ether ketone) (PEEK) discs (d = 8.5 mm x t = 2 mm). The results of this study confirmed that the SMP scaffolds were biocompatible and highly conducive to bone formation and ingrowth at the perimeter. Ultimately, this resulted in similar bone volume and surface area versus untreated defects and superior performance in push-out testing versus defects treated with PEEK discs. STATEMENT OF SIGNIFICANCE: Current treatments of craniomaxillofacial (CMF) bone defects include biologic and synthetic grafts but they are limited in their ability to form good contact with adjacent tissue. A regenerative engineering approach using a biologic-free scaffold able to achieve conformal fitting represents a potential "off-the-shelf" surgical product to heal CMF bone defects. Having not yet been evaluated in vivo, this study provided the preliminary assessment of the bone healing potential of self-fitting PCL scaffolds using a rabbit calvarial defect model. The study was designed to assess scaffold biocompatibility as well as bone formation and ingrowth using histology, micro-CT, and biomechanical push-out tests. The favorable results provide a basis to pursue establishing self-fitting scaffolds as a treatment option for CMF defects.
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Project description:Microarray analysis of gene expression was performed in the healing and non-healing calvarial defects of 12-week old male rats during various stages of bone repair: 1, 3, 5, 7, 10, 14, and 21 days post surgery.
2010-03-25 | GSE20980 | GEO
Project description:So far, how to achieve the optimal regenerative repair of large load-bearing bone defects using artificial bone grafts is a huge challenge in clinic. In this study, a strategy of combining osteoinductive biphasic calcium phosphate (BCP) bioceramic scaffolds with intramedullary nail fixation for creating stable osteogenic microenvironment was applied to repair large segmental bone defects (3.0 cm in length) in goat femur model. The material characterization results showed that the BCP scaffold had the initial compressive strength of over 2.0 MPa, and total porosity of 84%. The cell culture experiments demonstrated that the scaffold had the excellent ability to promote the proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs). The in vivo results showed that the intramedullary nail fixation maintained the initial stability and structural integrity of the implants at early stage, promoting the osteogenic process both guided and induced by the BCP scaffolds. At 9 months postoperatively, good integration between the implants and host bone was observed, and a large amount of newborn bones formed, accompanying with the degradation of the material. At 18 months postoperatively, almost the complete new bone substitution in the defect area was achieved. The maximum bending strength of the repaired bone defects reached to the 100% of normal femur at 18 months post-surgery. Our results demonstrated the good potential of osteoinductive BCP bioceramics in the regenerative repair of large load-bearing bone defects. The current study could provide an effective method to treat the clinical large segmental bone defects.
| S-EPMC8668427 | biostudies-literature
Project description:The restoration of cranio-maxillofacial deformities often requires complex reconstructive surgery in a challenging anatomical region, with abnormal soft tissue structures and bony deficits. In this proof-of-concept, the possibility of vertical bone augmentation was explored by suspending hemispherically shaped titanium-reinforced porous calcium phosphate (CaP) implants (n = 12) over the frontal bone in a sheep model (n = 6). The animals were euthanized after week 13 and the specimens were subject to micro-computed tomography (μCT) and comprehensive histological analysis. Histology showed that the space between implant and the recipient bone was filled with a higher percentage of newly formed bone (NFB) versus soft tissue with a median of 53% and 47%, respectively. Similar results were obtained from the μ-CT analysis, with a median of 56% NFB and 44% soft tissue filling the void. Noteworthy, significantly higher bone-implant contact was found for the CaP (78%, range 14%-94%) versus the Titanium (29%, range 0%-75%) portion of the implant exposed to the surrounding bone. The histological analysis indicates that the CaP replacement by bone is driven by macrophages over time, emphasized by material-filled macrophages found in close vicinity to the CaP with only a small number of single osteoclasts found actively remodeling the NFB. This study shows that CaP based implants can be assembled with the help of additive manufacturing to guide vertical bone formation without decortification or administration of growth factors. Furthermore, it highlights the potential disadvantage of a seamless fit between the implant and the recipient's bone.
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