Tissue engineering strategies for promoting vascularized bone regeneration

Abstract

This review focuses on current tissue engineering strategies for promoting vascularized bone regeneration. We review the role of angiogenic growth factors in promoting vascularized bone regeneration and discuss the different therapeutic strategies for controlled/sustained growth factor delivery. Next, we address the therapeutic uses of stem cells in vascularized bone regeneration. Specifically, this review addresses the concept of co-culture using osteogenic and vasculogenic stem cells, and how adipose derived stem cells compare to bone marrow derived mesenchymal stem cells in the promotion of angiogenesis. We conclude this review with a discussion of a novel approach to bone regeneration through a cartilage intermediate, and discuss why it has the potential to be more effective than traditional bone grafting methods.

Notch Signaling Augments BMP9-Induced Bone Formation by Promoting the Osteogenesis-Angiogenesis Coupling Process in Mesenchymal Stem Cells (MSCs)

“…Clinically the lack of vascularity results in poor integration between bone grafts and host bone and is the main cause for the failure of bone autografts or allografts [2, 3]. Thus, promoting vascularization by optimizing effective osteogenesis-angiogenesis coupling is essential for bone formation and bone tissue engineering [3].…”

“…Effective bone formation requires a well-coordinated coupling of osteogenesis and angiogenesis in a 3-D microenvironment [2, 36-39]. In fact, a close spatial–temporal association exists between the processes of angiogenesis and osteogenesis during skeletal development and postnatal bone growth, as well as during healing of bone fractures [38].…”

“…Most surgical interventions involve the use of autograft, which causes significant donor site morbidity, and is limited in availability. The use of alternative allograft for repairing extensive bone defects is also limited by the possibility of infection and host immunological reactions [2]. Thus, effective bone tissue engineering using stem cells, osteoinductive factors and biocompatible scaffold materials holds great promise in the treatment of extensive bone defects [1, 3-6].…”

The Use of Adipose Tissue-Derived Progenitors in Bone Tissue Engineering - a Review

“…MSCs are defined as plastic culture adhesive cells with an inherent characteristic to be colonogenic and multipotent and can differentiate into several mesodermal cell lineages including osteoblasts, chondrocytes, adipocytes, tenocytes, and myoblasts. MSCs are typically identified by their expression of CD90, CD105, CD73 and CD146, and the absence of CD45, CD34, CD14, CD11b, CD79a, CD19 and HLA-DR [17]. A common source for aspirating the MSCs is the iliac crest.…”

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

“…The most commonly adopted approach is the direct conversion of MSCs in the engineered construct to bone forming cells, the deposition of bone specific matrix followed by its mineralization through simulating the process of intramembranous ossification. 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] .…”