Abstract
To develop cost-effective and efficient bone substitutes for improved regeneration of bone defects, heparin-modified mineralized collagen scaffolds were functionalized with concentrated, naturally occurring bioactive factor mixtures derived from adipose tissue, platelet-rich plasma and conditioned medium from a hypoxia-treated human bone marrow-derived mesenchymal stem cell line. Besides the analysis of the release kinetics of functionalized scaffolds, the bioactivity of the released bioactive factors was tested with regard to chemotaxis and angiogenic tube formation. Additionally, functionalized scaffolds were seeded with human bone marrow-derived mesenchymal stromal cells (hBM-MSC) and their osteogenic and angiogenic potential was investigated. The release of bioactive factors from the scaffolds was highest within the first 3 days. Bioactivity of the released factors could be confirmed for all bioactive factor mixtures by successful chemoattraction of hBM-MSC in a transwell assay as well as by the formation of prevascular structures in a 2D co-culture system of hBM-MSC and human umbilical vein endothelial cells. The cells seeded directly onto the functionalized scaffolds were able to express osteogenic markers and form tubular networks. In conclusion, heparin-modified mineralized collagen scaffolds could be successfully functionalized with naturally occurring bioactive factor mixtures promoting cell migration and vascularization.
Highlights
Critical size bone defects caused by trauma, implant-related complications, tumor resection or infection represent an unsolved problem in orthopedic and trauma surgery
In order to achieve the highest possible protein concentration in the scaffolds, which is reliably detectable by enzyme-linked immunosorbent assay (ELISA) after release from the scaffolds, the bioactive factor mixtures were concentrated before loading the scaffolds
The aim of this study was to investigate a scaffold-based approach for a potential clinical application of bioactive factor mixtures derived from platelet lysate (PL), hypoxiaconditioned medium (HCM) and adipose tissue extract (ATE), which has been previously reported to exert chemoattractive, angiogenic and/or osteogenic effects [19]
Summary
Critical size bone defects caused by trauma, implant-related complications, tumor resection or infection represent an unsolved problem in orthopedic and trauma surgery. Due to their intrinsic osteogenic potential and the absence of the risk of immunological rejection, bone autografts are the gold standard for the repair of such defects. The tissue engineering concept provides an alternative treatment option: A porous scaffold consisting of a biodegradable bone substitute is colonized with autologous (stem) cells. Their osteogenic differentiation and maturation are stimulated by osteoinductive factors. The key challenges of this in situ tissue engineering approach are to identify suitable signaling factors and to ensure their efficient integration into a suitable bone replacement material as well as their sustained release
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