Biofabrication and Bone Tissue Regeneration: Cell Source, Approaches, and Challenges

Abstract

The growing occurrence of bone disorders and the increase in aging population have resulted in the need for more effective therapies to meet this request. Bone tissue engineering strategies, by combining biomaterials, cells, and signaling factors, are seen as alternatives to conventional bone grafts for repairing or rebuilding bone defects. Indeed, skeletal tissue engineering has not yet achieved full translation into clinical practice because of several challenges. Bone biofabrication by additive manufacturing techniques may represent a possible solution, with its intrinsic capability for accuracy, reproducibility, and customization of scaffolds as well as cell and signaling molecule delivery. This review examines the existing research in bone biofabrication and the appropriate cells and factors selection for successful bone regeneration as well as limitations affecting these approaches. Challenges that need to be tackled with the highest priority are the obtainment of appropriate vascularized scaffolds with an accurate spatiotemporal biochemical and mechanical stimuli release, in order to improve osseointegration as well as osteogenesis.

The effect of nacre extract on cord blood‐derived endothelial progenitor cells: A natural stimulus to promote angiogenesis?

“…Then, angiogenesis constitutes a critical point in bone tissue engineering. Indeed, the survival of the newly formed tissue depends on the vascular supply in this new bone . Strategies have been suggested to accelerate angiogenesis .…”

“…However, these surgeries involve important financial costs and present some significant limits such as significant post‐operative morbidity, the need for an additional invasive procedure (second site), a limited availability and a resorption that is difficult to anticipate . These limitations have induced the development of bone substitutes such as allograft, xenograft and alloplastic materials . However, these techniques produce unsatisfactory results especially regarding the lack of vascularization in the new‐formed bone .…”

Induced pluripotent stem cells (iPSCs) as a new source of bone in reconstructive surgery: A systematic review and meta-analysis of preclinical studies

“…Current techniques for the repair of large defects, which include the use of splints, distraction osteogenesis, or bone grafts, have limited clinical potential, and new approaches are required to overcome the disadvantages of such treatments. Recently, due to the growing occurrence of bone defects, orthopaedic and maxillofacial surgeons have been involved in research landscape helping to translate basic research into clinical practice to benefit the patients (De Peppo et al, ; Orciani, Fini, Di Primio, & Mattioli‐Belmonte, ). Bone tissue engineering had emerged as an unlimited source for bone regeneration without complications of other bone reconstruction modalities.…”

Advances in three‐dimensional bioprinting of bone: Progress and challenges

“…Current strategy is to implant synthetic bone grafts, which often fail in the case of critical‐sized defects as the peripheral vasculature does not reach the core of the construct. Therefore, the formation of congruent bone largely depends upon the development of a functional vascular system, which remains a big hurdle in the biofabrication of human‐scale constructs (Orciani et al, ).…”

“…Mechanical compliance pertaining to cortical (100 MPa)/cancellous bone (3-4 MPa;Misch, Qu, & Bidez, 1999), replicating the dynamic bone micro-environment in terms of consistent fluid flow and hypoxic bone marrow similar to in vivo conditions (Rankin, Giaccia, & Schipani, 2011;Spencer et al, 2014), are also relatively less explored. There are challenges associated with establishing branched vasculature for nutrient perfusion and metabolic waste removal, optimization of the cell source such as adult stem cells/fetal stem cells/induced pluripotent stem cells (Leberfinger, Ravnic, Dhawan, & Ozbolat, 2017;Orciani, Fini, di Primio, & Mattioli-Belmonte, 2017), and mimicking the complex interplay and crosstalk between the various biological moieties (bone morphogenetic protein [BMP]-2, BMP-4, vascular endothelial growth factor [VEGF]) for inducing bone signalling (Notch, Wnt/β-Catenin, BMP; Midha, Murab, & Ghosh, 2016).…”