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.

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 |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

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.

Project description:Bisphosphonates (BP) are anti-resorptive drugs that are widely used to prevent bone loss in osteoporosis. Since inhibition of bone resorption will cause a decrease in bone formation through a process called coupling, it is hypothesized that extended treatment protocols may impair bone healing. In this study, β-tri‑calcium-phosphate (βTCP) ceramics were inserted into critical-size long bone defects in estrogen-deficient mice under BP therapy. The study assessed the benefits of coating the ceramics with Bone Morphogenetic Protein-2 (BMP2) and an engineered BMP2 analogue (L51P) that inactivates BMP antagonists on the healing process, implant resorption, and bone formation. Female NMRI mice (11-12 weeks of age) were ovariectomized (OVX) or sham operated. Eight weeks later, after the manifestation of ovariectomy-induced osteoporotic bone changes, BP therapy with Alendronate (ALN) was commenced. After another five weeks, a femoral critical-size defect was generated, rigidly fixed, and βTCP-cylinders loaded with 0.25 μg or 2.5 μg BMP2, 2.5 μg L51P, and 0.25 μg BMP2/2.5 μg L51P, respectively, were inserted. Unloaded βTCP-cylinders were used as controls. Femora were collected six and twelve weeks post-implantation. Histological and micro-computer tomography (MicroCT) evaluation revealed that insertion of cylinders coated with 2.5 μg BMP2 accelerated fracture repair and induced significant bone formation compared to controls (unloaded cylinders or coated with 2.5 μg L51P, 0.25 μg BMP2) already six weeks post-implantation, independent of estrogen-deficiency and BP therapy. The simultaneous administration of BMP2 and L51P (0.25 μg BMP2/2.5 μg L51P) did not promote fracture healing six and twelve weeks post-implantation. Moreover, new bone formation within the critical-size defect was directly linked to the removal of the βTCP-implant in all experimental groups. No evidence was found that long-term therapy with ALN impaired the resorption of the implanted graft. However, osteoclast transcriptome signature was elevated in sham and OVX animals upon treatment with BP, with transcript levels being higher at six weeks than at twelve weeks post-surgery. Furthermore, the transcriptome profile of the developing repair tissue confirmed an accelerated repair process in animals treated with 2.5 μg BMP2 implants. L51P did not increase the bioefficacy of BMP2 in the applied defect model. The present study provides evidence that continuous administration of BP does not inhibit implant resorption and does not alter the kinetics of the healing process of critical-size long bone defects. Furthermore, the BMP2 variant L51P did not enhance the bioefficacy of BMP2 when applied simultaneously to the femoral critical-size defect in sham and OVX mice.

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets