New in situ Tissue Engineering approach - Scaffold functionalization with a central, growth factor-loaded depot for cell attraction and stimulation of angiogenesis in BoneWednesday (10.05.2017) 15:40 - 16:00 Part of:
In terms of clinical translation classical tissue engineering approaches are still limited by the lack of vascularization leading to an insufficient oxygen and nutrient supply of cells in inner scaffold regions. In this study, mineralized collagen1 served as porous biomimetic scaffolds, which was functionalized with a central, growth factor-loaded hydrogel-depot in order to promote angiogenesis and to attract cells with regenerative potential. In these depots an autologous growth factor mix, generated from hypoxia conditioned medium (HCM) from human mesenchymal stroma cells (hMSC), was integrated. Through a gradually release of chemoattractive and angiogenic factors, angiogenesis and cell migration will be attracted towards the central depot. The promotion of cellular ingrowth and vascularization would contribute to an accelerated bone defect healing (in situ tissue engineering).
Mineralized collagen scaffolds were functionalized with HCM, generated by hypoxia treated hMSC (72 h; 1 % O2)2.For depot integration (injection), HCM was concentrated (dialysed; freeze dried) and resuspended in different biopolymers to facilitate various release kinetics. Scaffolds were cultivated with a coculture of hMSC and endothelial cells (HUVEC) and the formed prevascular networks (CD31-stained) were analysed regarding length, branching and penetration depth of the tube structures into the scaffold.
Hypoxia treated hMSC secreted various angiogenic growth factors (mainly VEGF: 25 - 35 ng/ mL), which highly stimulated cell migration and angiogenesis. Compared to VEGF-loaded depots (100 ng; Positive-Control), scaffolds functionalized with HCM showed clearly more dense prevascular networks on the scaffold surfaces and tube structures, sprouting deeper throughout the interconnected pore system towards the central depot. Our findings indicate that HCM is a potent alternative to recombinant VEGF for stimulate angiogenesis and cell migration. Its integration in a central depot is therefore a promising strategy to foster an accelerated bone defect healing.
1. Gelinsky M. et al. Chem Eng J. 137, 84, 2008.
2. Gabrielyan A. et al. BMC Veterinary Research 10, 1, 2014.