Improvement of bone regeneration using fibrin biopolymer combined with differentiated stem cells

Abstract

1.ABSTRACTBone tissue repair remains a challenge on tissue engineering. New approaches are highly expected to regenerate fractures, bone infections, cancers and congenital skeletal abnormalities. Lately, osteoconductive biomaterials have been used with osteoprogenitor cellsas bone substitutes to accelerate bone formation. Fibrin scaffold serves as a provisional platform promoting cell migration and proliferation, angiogenesis, connective tissue formation and growth factors stimulation. When combined with mesenchymal stem cells (MSCs) maintain cell viability that exerts an immunomodulatory effect by modifying inflammatory environment through expression of pro and anti-inflammatory cytokines. We evaluated a unique heterologous fibrin biopolymer as scaffold to MSCs on bone regeneration of rat femurs. A critical-size bone defect was made in the femur and treated with fibrin biopolymer(FBP); FBP + MSC; and FBP + MSC differentiated in bone lineage (MSC-D). Bone repair was analyzed 03, 21 and 42 days later by radiographic, histological and scanning electron microscopy (SEM) imaging. The FBP+MSC-D association was the most effective treatment, since newly formed bone was more abundant and early matured in just 21 days. Our results demonstrate that FBP isolated was able to promote bone repair although cells play a crucial role on the type and quantity of bone tissue formed. We have not observed surgical site infection, inflammatory response, fractures or loss of function related with FBP. Thus, this approach can be safely expanded for clinical trials as an effort to overcome current method limitations and improve overall bone regeneration process.