Decellularized Cortical Bone Scaffold Promotes Organized Neovascularization In Vivo

Abstract

Significant bone loss due to disease or traumatic injury requires surgical intervention to modulate the natural healing process of bone. The current bone grafting options, autografts and allografts, can potentially lead to donor site morbidity or mechanical failure over time. The use of tissue engineering is a promising alternative, but the mechanical stability and integrated vasculature in vivo still remains a major challenge. In this work, we introduce a scaffold that mimics the cylindrical structure of native cortical bone and provides biological cues without the addition of growth factors to promote stem cell differentiation along the angiogenic lineage. Biocompatibility of the scaffold was tested with two human endothelial cell types, human microvascular endothelial cells and human umbilical vein endothelial cells, and the angiogenic decellularized scaffold matrix led to a 78% increase in angiogenic protein secretion from human bone marrow-derived stem cells. Histological analysis of the scaffolds implanted subcutaneously in the dorsum of BALB/c mice confirmed vessel development and integration at 4 weeks with a decrease in fibrous capsule thickness up to 8 weeks. Future work will need to be performed to evaluate this novel scaffold as a vascularized tissue-engineered graft in a large animal model.

Characterization of a prevascularized biomimetic tissue engineered scaffold for bone regeneration

“…Overall, mechanical properties, osteoinduction, and angioinduction are the primary concerns recognized in the current state of the art (Brown & Badylak, ; Moore et al, ; Novosel et al, ). The scaffold's mechanical properties are similar to that of trabecular bone due to the inclusion HAp posts, and further improvements have been demonstrated by our group as well (Taylor et al, ). The fibrous, bone mimicking structure in addition to the mineral content of the scaffold creates an osteoinductive environment, and the results of this study reinforce the results seen in previous studies (Andric et al, ; Andric, Sampson, & Freeman, ; Andric, Wright, & Freeman, ; Taylor, ; Taylor et al, ; Wright et al, ).…”

“…This is an indication that prevascularization does have a positive effect on hMSC differentiation toward a vascular lineage. There are many cell types, including MSC, that are capable of producing VEGF, but our previous studies show that MSC under similar culture conditions produced significantly less VEGF on scaffolds that did not have ECM from vascular endothelial cells compared to those cultured on scaffolds with ECM from vascular endothelial cells (Taylor et al, ). Alkaline phosphatase stain was observed in both the TCP group and scaffold groups at all time points.…”

“…However, these trends do point to the potential utility of prevascularization in graft vascular development. There was no additional group with decellularized scaffolds and no cells to measure residual CD31 and VE cadherin because we performed a similar study measuring residual VEGF on decellularized scaffolds and found none (Taylor et al, ).…”

Mineralization of Biomaterials for Bone Tissue Engineering

“…Although the utilization of bone grafts has had limited success in clinical practice, these costly procedures have complications, including risk of infection, graft rejection, and weak osteoinductivity. Therefore, there is a clinical demand for safe, cost-effective, and reliable alternatives to the current bone grafting materials and techniques [ 20 ].…”

Preservation of the naïve features of mesenchymal stromal cells in vitro: Comparison of cell- and bone-derived decellularized extracellular matrix

“… 33 Decellularized tissue constructs have been successfully applied for several years in tissue engineering and regenerative medicine, mainly designed for rather simple tissues, for example, heart valve substitutes, 34 , 35 skin grafts, 36 , 37 bladder mucosa grafts, 38 , 39 etc. Particularly, decellularized bone ECM-derived constructs – for example, (1) in vitro MSC-produced decellularized ECM constructs 40 and (2) bioactive 3D scaffolds originated from trabecular 41 , 42 or cortical decellularized bone 43 — have gained a lot of interest as implantable biomaterials for bone tissue repair and regeneration, due to their biochemical properties and their unique mechanical properties and architecture.…”