Angiogenesis-promoting composite TPMS bone tissue engineering scaffold for mandibular defect regeneration

Abstract

Mandibular defects severely impact the patient’s quality of life and are difficult problems to treat in the clinical setting. Due to the limitations of current gold-standard therapies, there is a tremendous need for tissue engineering approaches to meet this rising clinical demand. Injectable platelet-rich fibrin (I-PRF) containing a variety of pro-regenerative growth factors and stromal cell-derived factor-1 (SDF-1) has been shown to be beneficial in stimulating angiogenesis. In this study, we developed a three-cycle minimally curved biomimetic bone tissue engineering scaffold made of β-tricalcium phosphate, modified with I-PRF and SDF-1. I-PRF was loaded at a concentration of 5% onto a triply periodic minimal surface (TPMS) scaffold with a porosity of 70%. CCK-8 experiments and live-dead staining confirmed the scaffold’s good biocompatibility and its ability to promote cell proliferation. Wound healing assays showed that the TPMS scaffold loaded with I-PRF and SDF-1 (SIT) enhanced cell migration of MC3T3 cells. Moreover, angiogenesis experiments showed that the SIT scaffold promoted angiogenesis. Importantly, alkaline phosphatase and alizarin red staining confirmed that the bone scaffold accelerated MC3T3 cells’ osteogenic differentiation and mineralization. The SIT bone scaffold was then implanted into a rabbit mandible defect model. After a 2-month post-implantation period, micro- CT analysis revealed the growth of new bone tissue around the SIT construct, while histological analysis which included hematoxylin-eosin (H&E) staining and masson’s trichrome staining, alkaline phosphatase (ALP) staining, osteoprotegerin (OPG) staining demonstrated that the SIT scaffold substantially promoted the growth of a highly vascularized fibrous and bone tissue in the defect site. Taken together, these findings demonstrate the considerable potential of TPMS scaffolds loaded with I-PRF and SDF-1 in promoting the repair of mandible defects.