Recapitulating endochondral ossification: a promising route toin vivobone regeneration

Abstract

Despite its natural healing potential, bone is unable to regenerate sufficient tissue within critical-sized defects, resulting in a non-union of bone ends. As a consequence, interventions are required to replace missing, damaged or diseased bone. Bone grafts have been widely employed for the repair of such critical-sized defects. However, the well-documented drawbacks associated with autografts, allografts and xenografts have motivated the development of alternative treatment options. Traditional tissue engineering strategies have typically attempted to direct in vitro bone-like matrix formation within scaffolds prior to implantation into bone defects, mimicking the embryological process of intramembranous ossification (IMO). Tissue-engineered constructs developed using this approach often fail once implanted, due to poor perfusion, leading to avascular necrosis and core degradation. As a result of such drawbacks, an alternative tissue engineering strategy, based on endochondral ossification (ECO), has begun to emerge, involving the use of in vitro tissue-engineered cartilage as a transient biomimetic template to facilitate bone formation within large defects. This is driven by the hypothesis that hypertrophic chondrocytes can secrete angiogenic and osteogenic factors, which play pivotal roles in both the vascularization of constructs in vivo and the deposition of a mineralized extracellular matrix, with resulting bone deposition. In this context, this review focuses on current strategies taken to recapitulate ECO, using a range of distinct cells, biomaterials and biochemical stimuli, in order to facilitate in vivo bone formation.

Gene Delivery of TGF-β3 and BMP2 in an MSC-Laden Alginate Hydrogel for Articular Cartilage and Endochondral Bone Tissue Engineering

“…A major concern with the use of MSCs for articular cartilage regeneration is their inherent tendency to progress towards hypertrophy and endochondral ossification or to undergo fibrous dedifferentiation 2,5 . However, this inherent potential of chondrogenically primed MSCs to become hypertrophic can be leveraged for endochondral bone tissue engineering, which aims to recapitulate embryonic skeletal development in order to engineer fully functional bone tissue [6][7][8][9][10] . Ultimately, it is important to be able to control the MSC phenotype towards a particular target application (e.g.…”

Tissue engineering strategies for promoting vascularized bone regeneration

“…The lack of a vascular network hinders the delivery of nutrients and the removal of waste from the center of current bone grafts and tissue engineered constructs 190 . As a result these bone grafts are met with a number of failure mechanisms, such as, loss of mechanical strength over time, poor osseointegration, and osteonecrosis of the graft.…”

RALA complexed α-TCP nanoparticle delivery to mesenchymal stem cells induces bone formation in tissue engineered constructs in vitro and in vivo

“…This is commonly implemented by employing hydrogels or scaffolds loaded or stimulated with growth factors that induce osteogenic differentiation of the incorporated or recruited MSCs [5][6][7][8] . An alternative approach is the engineering of a hypertrophic cartilaginous template by inducing chondrogenic lineage differentiation in bone marrow derived MSCs in order to recapitulate the developmental process of endochondral ossification [9][10][11] .…”