Synthesis and characterization of biodegradable hybride polyester-polyacrylate nanogels containing PDGF as an injectable scaffold for cartilage repair

Abstract

Introduction: Articular cartilage has limited self-regeneration ability for lacking of blood vessels and nerves that makes it a great challenge to repair defects of the musculoskeletal injuries in regenerative medicine. Aims: The goal of the present study was to create a new biodegradable hybrid thermosensitive hydrogel scaffold to promote the proliferation and chondrogenic differentiation of human adipose tissue derived mesenchymal stem cells in the presence of the PDGF_BB.Methods: In this study, PCL-P(HEMA-NIPAAm) nanohydrogel hybrid scaffold based on polyester-acrylate that loaded with PDGF_BB was designed. The physicochemical properties of the scaffold such as LCST, swelling ratio, hydrolytic degradation, water contact angle, mechanical properties, morphology and release of growth factor were evaluated. After isolation, hASCs were identified by flow cytometric. The biocompatibility, proliferation and adhesion of cells seeded on scaffold was evaluated by SEM and MTT assay. Gene expression of chondrocyte-specific markers was evaluated by RT-PCR.Results: According to the LCST values, S-2, reaching 37 °C, was selected for different in vitro assays. SEM imaging showed nanoparticulate structure of the scaffold with 85±45 µm pore size. Compressive strength, Young’s modulus, and compressive strain (%) of S-2 were 52.5 MPa, 0.7 MPa, and 75.5%. A sustained release of PDGF-BB from scaffold (around 90%) was demonstrated. The scaffold was found to be non-toxic and allow good adhesion and proliferation of cells after 14 days. RT-PCR analysis demonstrated that the combination of scaffold and PDGF-BB promoted the chondrogenesis of hASCs by up-regulating the expression of aggrecan, type-II collagen, SOX-9, and integrin β1 compared with the non-treated control group. Conclusion: The results demonstrate that the PCL-P(HEMA-NIPAAm) nano-hydrogel scaffold carrying PDGF-BB as a matrix for hASCs seeding is a valuable system that may be used in the future as a three-dimensional construct for implantation in cartilage injuries.