Tissue Engineering and Cell-Based Therapies for Fractures and Bone Defects

Abstract

Bone fractures and segmental bone defects are a significant source of patient morbidity and place a staggering economic burden on the healthcare system. The annual cost of treating bone defects in the US has been estimated to be $5 billion, while enormous costs are spent on bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. Autologous bone grafts represent the gold standard for the treatment of bone defects. However, they are associated with variable clinical outcomes, postsurgical morbidity, especially at the donor site, and increased surgical costs. In an effort to circumvent these limitations, tissue engineering and cell-based therapies have been proposed as alternatives to induce and promote bone repair. This review focuses on the recent advances in bone tissue engineering (BTE), specifically looking at its role in treating delayed fracture healing (non-unions) and the resulting segmental bone defects. Herein we discuss: (1) the processes of endochondral and intramembranous bone formation; (2) the role of stem cells, looking specifically at mesenchymal (MSC), embryonic (ESC), and induced pluripotent (iPSC) stem cells as viable building blocks to engineer bone implants; (3) the biomaterials used to direct tissue growth, with a focus on ceramic, biodegradable polymers, and composite materials; (4) the growth factors and molecular signals used to induce differentiation of stem cells into the osteoblastic lineage, which ultimately leads to active bone formation; and (5) the mechanical stimulation protocols used to maintain the integrity of the bone repair and their role in successful cell engraftment. Finally, a couple clinical scenarios are presented (non-unions and avascular necrosis—AVN), to illustrate how novel cell-based therapy approaches can be used. A thorough understanding of tissue engineering and cell-based therapies may allow for better incorporation of these potential therapeutic approaches in bone defects allowing for proper bone repair and regeneration.

Bone tissue regeneration: biology, strategies and interface studies

“…Endochondral bone tissue engineering using progenitor cells such as chondroprogenitors has been lately demonstrated. Several researches presented that articular chondrocytes are able to be stimulated to endochondral ossification and generate TGFβ-1 and BMP-2 (Perez et al 2018). In a study, chondrocyte cell seeded on BMP-2-loaded polycaprolactone (PCL) scaffold which subcutaneously implanted in vivo result in bone formation (Lee and Shin 2007).…”

Developments in Antibiotic-Eluting Scaffolds for the Treatment of Osteomyelitis

“…One way in which this can be done is by filling the bony defect(s) with a bone graft, material such as polymethyl methacrylate or a scaffold to prevent haematoma formation. In the United States (US) alone, the annual cost of treating bone defects has been estimated to be $5 billion [16].…”

A novel method to improve the osteogenesis capacity of hUCMSCs with dual‐directional pre‐induction under screened co‐culture conditions

“…Autologous bone grafts, routinely regarded as the “golden standard” for bone transplantation, require a second surgical site, inevitably causing new tissue damages and bringing seriously physical, psychological and economic burdens to patients . To attain non‐invasive and much safer customized rehabilitation of bone defects, mesenchymal stem cells (MSCs) have been suggested to facilitate the fabrication of customized, bioactive tissue‐engineered bone grafts based on the bone scaffold made by three‐dimensional printing (3DP), so as to provide promising evidence for clinical settings . To date, with the in‐depth study, MSCs are extensively used as seed cells for bone tissue regeneration, especially MSCs isolated from bone marrow, characterize better osteogenic differentiation capacity and are frequently used in bone tissue engineering .…”