Bone defect reconstruction via endochondral ossification: A developmental engineering strategy

Abstract

Traditional bone tissue engineering (BTE) strategies induce direct bone-like matrix formation by mimicking the embryological process of intramembranous ossification. However, the clinical translation of these clinical strategies for bone repair is hampered by limited vascularization and poor bone regeneration after implantation in vivo. An alternative strategy for overcoming these drawbacks is engineering cartilaginous constructs by recapitulating the embryonic processes of endochondral ossification (ECO); these constructs have shown a unique ability to survive under hypoxic conditions as well as induce neovascularization and ossification. Such developmentally engineered constructs can act as transient biomimetic templates to facilitate bone regeneration in critical-sized defects. This review introduces the concept and mechanism of developmental BTE, explores the routes of endochondral bone graft engineering, highlights the current state of the art in large bone defect reconstruction via ECO-based strategies, and offers perspectives on the challenges and future directions of translating current knowledge from the bench to the bedside.

The Osteoinductivity of Calcium Phosphate-Based Biomaterials: A Tight Interaction With Bone Healing

“…Mature hypertrophic chondrocytes undergo apoptosis or transition into osteoblast-like cells, which together with osteoblasts, contribute to the secretion of type I collagen and the extracellular matrix (ECM) mineralization. Finally, the soft callus is transformed into the disordered woven bone ( Tsang et al, 2015 ; Fu et al, 2021 ). Once the periosteum and adjacent soft tissue regions are injured, the MSCs recruited from the periosteum, bone marrow, adjacent soft tissues, and peripheral circulation and osteoprogenitor cells within the periosteum initiate the intramembranous bone formation process.…”

Cutting Edge Endogenous Promoting and Exogenous Driven Strategies for Bone Regeneration

“…In fact, bone fracture healing relying on mesenchymal stem cells (MSCs) derived osteoblasts performance, can occur through two different mechanisms: intramembranous (involved in the formation of flat bones such as skull bones and clavicles) and endochondral (in long bones such as femur and tibia) bone formation. While the intramembranous ossification directly forms the bone from MSCs that are differentiated into osteoblasts, for endochondral bone formation, there are two key players required; the presence of cartilage, and the vascularization process [2,3]. Indeed, angiogenesis (the formation of new blood vessels from pre-existing ones) is a key component in bone repair, since blood vessels bring oxygen and nutrients to the regenerating tissue [4].…”

Constructing a cell microenvironment with biomaterial scaffolds for stem cell therapy

“…Furthermore, a study of MSCs that entrap a specific macrophage immunophenotypes with the gelatin/polyethylene glycol-based matrix has indicated a considerable improvement in adipocyte differentiation and further promotes normal wound healing [ 80 ]. Advances in developmental engineering strategies with the capacity to construct a suitable microenvironment for stem cell-based therapy, protein replacements, or gene therapies may pave the way for some incurable diseases, such as rare genetic epidermolysis bullosa (EB) [ 81 ], and bone grafting [ 82 ].

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