Review of vascularised bone tissue-engineering strategies with a focus on co-culture systems

Abstract

Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings.

Low power laser irradiation and human adipose-derived stem cell treatments promote bone regeneration of critical-sized calvarial defects in rats

“…The results are consistent with many preceding studies providing robust scientific evidence on the osteogenic potency of ADSCs and their ability to promote bone repair and regeneration in vivo [40][41][42][43][44]. ADSCs have great potential for bone regeneration due to their many appreciated features, including their increased accessibility and resistance to senescence and malignant transformation [45][46][47].…”

Platelet-Derived Growth Factor and Spatiotemporal Cues Induce Development of Vascularized Bone Tissue by Adipose-Derived Stem Cells

“…This problem is a fundamental challenge for all approaches toward engineering a vascularized bone graft, including those that involve the combination of osteoblasts or mesenchymal stem cells (MSCs) with a separate endothelial cell source. 24 Our prior studies showed that vascular assembly of ASCs is dependent on heterotypic cell-cell interactions, specifically through dense clustering of cells and endogenous plateletderived growth factor (PDGF) signaling. This endogenous behavior is reminiscent of what occurs in native tissues, as proliferating endothelial cells in nascent vessels secrete PDGF-BB to recruit pericytes for vascular maturation and stabilization.…”

Dual-Phase Osteogenic and Vasculogenic Engineered Tissue for Bone Formation

“…[7][8][9][10] Cell-based approaches to vascularized bone tissue engineering also are being pursued. [11][12][13] Numerous studies have shown that coculture of endothelial cells and osteogenic cells allows the formation of both vascular networks and mineralized tissue postimplantation. Kaigler et al implanted poly(lactide-co-glycolide) (PLGA) scaffolds containing a coculture of human microvascular endothelial cells (HMVEC) and bmMSC into immunodeficient mice and monitored ectopic bone formation over 8 weeks.…”