Fortified gelatin-based hydrogel scaffold with simvastatin-mixed nanomicelles and platelet rich plasma as a promising bioimplant for tissue regeneration

Abstract

Treatment of intervertebral disc (IVD) degeneration includes conservative and surgical strategies that have a high risk of recurrence. Consequently, tissue engineering represents a promising alternative treatment. This study aimed at healing damaged IVD with a bioimplant that can maintain the function of defected IVD. The developed IVD scaffold is composed of a fortified biocompatible gelatin-based hydrogel to mimic the ECM mechanical properties of IVD and to allow a sustained release of loaded bioactive agents. The hydrogel is laden with platelet-rich plasma (PRP) and simvastatin (SIM)-loaded mixed pluronics nanomicelles because of their regenerative ability and anti-inflammatory effect, respectively. The gelatin-based hydrogel attained swelling of 508.9 ± 7.9 % to 543.1 ± 5.9 % after 24 h. Increasing crosslinking degree of the hydrogel improved its mechanical elasticity up to 0.3 ± 0.1 N/mm², and retarded its degradation. The optimum mixed nanomicelles had particle size of 84 ± 0.5 nm, a surface charge of -10 ± 7.1 mv, EE% of 84.9 %, and released 88.4 % of SIM after 21 days. Cytotoxicity of IVD components was evaluated using human skin fibroblast for 3 days. WST-test results proved biocompatibility of IVD scaffold. Subcutaneous implantation of the IVD scaffold was performed for 28 days to test in-vivo biocompatibility. Histological and histochemical micrographs depicted normal healing signs such as macrophages, T-cells, angiogenesis and granulation reactions. Introducing PRP in IVD improved healing process and decreased inflammation reactions. The developed multicomponent implant could be used as potential IVD scaffold with desirable mechanical properties, biocompatibility and healing process.

Keywords: Gelatin; Hydrogel; Intervertebral disc degeneration; Nanomicelles; Platelet-rich plasma; Simvastatin; Spondylitis; Tissue engineering.