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Improved healing of critical-size femoral defect in osteoporosis rat models using 3D elastin/polycaprolactone/nHA scaffold in combination with mesenchymal stem cells.

ABSTRACT: Osteoporosis is a common bone disease that results in elevated risk of fracture, and delayed bone healing and impaired bone regeneration are implicated by this disease. In this study, Elastin/Polycaprolactone/nHA nanofibrous scaffold in combination with mesenchymal stem cells were used to regenerate bone defects. Cytotoxicity, cytocompatibility and cellular morphology were evaluated in vitro and observations revealed that an appropriate environment for cellular attachment, growth, migration, and proliferation is provided by this scaffold. At 3 months following ovariectomy (OVX), the rats were used as animal models with an induced critical size defect in the femur to evaluate the therapeutic potential of osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) seeded on 3 dimension (3D) scaffolds. In this experimental study, 24 female Wistar rats were equally divided into three groups: Control, scaffold (non-seeded BM-MSC), and scaffold + cell (seeded BM-MSC) groups. 30 days after surgery, the right femur was removed, and underwent a stereological analysis and RNA extraction in order to examine the expression of Bmp-2 and Vegf genes. The results showed a significant increase in stereological parameters and expression of Bmp-2 and Vegf in scaffold and scaffold + cell groups compared to the control rats. The present study suggests that the use of the 3D Elastin/Polycaprolactone (PCL)/Nano hydroxyapatite (nHA) scaffold in combination with MSCs may improve the fracture regeneration and accelerates bone healing at the osteotomy site in rats.

SUBMITTER: Hejazi F

PROVIDER: S-EPMC7940275 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Improved healing of critical-size femoral defect in osteoporosis rat models using 3D elastin/polycaprolactone/nHA scaffold in combination with mesenchymal stem cells.

Hejazi Fatemeh F Ebrahimi Vahid V Asgary Mehrdad M Piryaei Abbas A Fridoni Mohammad Javad MJ Kermani Ali Asghar AA Zare Fatemeh F Abdollahifar Mohammad-Amin MA

Journal of materials science. Materials in medicine 20210308 3

Osteoporosis is a common bone disease that results in elevated risk of fracture, and delayed bone healing and impaired bone regeneration are implicated by this disease. In this study, Elastin/Polycaprolactone/nHA nanofibrous scaffold in combination with mesenchymal stem cells were used to regenerate bone defects. Cytotoxicity, cytocompatibility and cellular morphology were evaluated in vitro and observations revealed that an appropriate environment for cellular attachment, growth, migration, and ...[more]

PMID: 33683483

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Project description:Background Composite scaffolds that maximize the advantages of different polymers are widely utilized in guided tissue regeneration (GTR). Some studies found that novel composite scaffolds composed of electrospun polycaprolactone/fluorapatite (ePCL/FA) actively promoted the osteogenic mineralization of various cell types in vitro. However, only a few studies have addressed the application of this composite scaffold membrane material in vivo. In this study, the ability of ePCL/FA composite scaffolds in vivo and their possible mechanisms were preliminarily explored. Methods In this study, ePCL/FA composite scaffolds were characterized and their effects on bone tissue engineering and repair of calvarial defects in rats were examined. Sixteen male Sprague-Dawley (SD) rats were randomly categorized into four groups: normal group (integral cranial structure without defect), control group (cranial defect), ePCL group (cranial defect repaired by electrospun polycaprolactone scaffolds), and ePCL/FA group (cranial defect repaired by fluorapatite-modified electrospun polycaprolactone scaffolds). At 1 week, 2 months, and 4 months, micro-computed tomography (micro-CT) analysis was performed to compare the bone mineral density (BMD), bone volume (BV), tissue volume (TV), and bone volume percentage (BV/TV). The effects of bone tissue engineering and repair were observed by histological examination (hematoxylin and eosin, Van Gieson, and Masson respectively) at 4 months. Results In water contact angle measurement, the average contact angle for the ePCL/FA group was significantly lower than that for the ePCL group, indicating that the FA crystal improved the hydrophilicity of the copolymer. Micro-CT analysis revealed that the cranial defect had no significant change at 1 week; however, the BMD, BV, and BV/TV of the ePCL/FA group were significantly higher than those of the control group at 2 and 4 months. Histological examination showed that the cranial defects were almost completely repaired by the ePCL/FA composite scaffolds at 4 months compared to the control and ePCL groups. Conclusions The introduction of a biocompatible FA crystal improved the physical and biological properties of the ePCL/FA composite scaffolds; thus, these scaffolds demonstrate outstanding osteogenic potential for bone and orthopedic regenerative applications.

Project description:Large skeletal muscle injuries, such as a volumetric muscle loss (VML), often result in an incomplete regeneration due to the formation of a non-contractile fibrotic scar tissue. This is, in part, due to the outbreak of an inflammatory response, which is not resolved over time, meaning that type-1 macrophages (M1, pro-inflammatory) involved in the initial stages of the process are not replaced by pro-regenerative type-2 macrophages (M2). Therefore, biomaterials that promote the shift from M1 to M2 are needed to achieve optimal regeneration in VML injuries. In this work, we used elastin-like recombinamers (ELRs) as biomaterials for the formation of non- (physical) and covalently (chemical) crosslinked bioactive and biodegradable hydrogels to fill the VML created in the tibialis anterior (TA) muscles of rats. These hydrogels promoted a higher infiltration of M2 within the site of injury in comparison to the non-treated control after 2 weeks (p<0.0001), indicating that the inflammatory response resolves faster in the presence of both types of ELR-based hydrogels. Moreover, there were not significant differences in the amount of collagen deposition between the samples treated with the chemical ELR hydrogel at 2 and 5 weeks, and this same result was found upon comparison of these samples with healthy tissue after 5 weeks, which implies that this treatment prevents fibrosis. The macrophage modulation also translated into the formation of myofibers that were morphologically more similar to those present in healthy muscle. Altogether, these results highlight that ELR hydrogels provide a friendly niche for infiltrating cells that biodegrades over time, leaving space to new muscle tissue. In addition, they orchestrate the shift of macrophage population toward M2, which resulted in the prevention of fibrosis in the case of the chemical hydrogel treatment and in a more healthy-like myofiber phenotype for both types of hydrogels. Further studies should focus in the assessment of the regeneration of skeletal muscle in larger animal models, where a more critical defect can be created and additional methods can be used to evaluate the functional recovery of skeletal muscle.

Dataset Information

Improved healing of critical-size femoral defect in osteoporosis rat models using 3D elastin/polycaprolactone/nHA scaffold in combination with mesenchymal stem cells.

Publications

Improved healing of critical-size femoral defect in osteoporosis rat models using 3D elastin/polycaprolactone/nHA scaffold in combination with mesenchymal stem cells.

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