Preparation and characterization of collagen-based ADSC-carrier sheets for cardiovascular application

The use of scaffolds composed of natural biodegradable matrices represents an attractive strategy to circumvent the lack of cell engraftment, a major limitation of stem cell therapy in cardiovascular diseases. Bovine-derived non-porous collagen scaffolds with different degrees of cross-linking (C0, C2, C5 and C10) were produced and tested for their mechanical behavior, in vitro biocompatibility with adipose-derived stem cells (ADSCs) and tissue adhesion and inflammatory reaction. Uniaxial tensile tests revealed an anisotropic behavior of collagen scaffolds (2 x 0.5 cm) and statistically significant differences in the mechanical behavior between cross-linked and non-cross-linked scaffolds (n = 5). In vitro, ADSCs adhered homogenously and showed a similar degree of proliferation on all four types of scaffolds (cells x 10(3) cm(-2) at day 7: C0: 94.7 +/- 37.1; C2: 91.7 +/- 25.6; C5: 88.2 +/- 6.8; C10: 72.8 +/- 10.7; P = n.s.; n = 3). In order to test the in vivo biocompatibility, a chronic myocardial infarction model was performed in rats and 1.2 x 1.2 cm size collagen scaffolds implanted onto the heart I month post-infarction. Six animals per group were killed 2, 7 and 30 days after transplant. Complete and long-lasting adhesion to the heart was only observed with the non-cross-linked scaffolds with almost total degradation 1 month post-transplantation. After 7 and 30 days post-implantation, the degree of inflammation was significantly lower in the hearts treated with non-cross-linked scaffolds (day 7: C0: 10.2 +/- 2.1%; C2: 163 +/- 2.9%; C5: 15.9 +/- 4.8%; C10: 17.4 +/- 4.1%; P < 0.05 vs. C0; day 30: C0: 1.3 +/- 1.3%; C2: 9.4 +/- 3.0%; C5: 7.0 +/- 2.1%; C10: 9.8 +/- 2.5%; P < 0.01 vs. C0). In view of the results, the non-cross-linked scaffold (C0) was chosen as an ADSC-carrier sheet and tested in vivo. One week post-implantation, 25.3 +/- 7.0% of the cells transplanted were detected in those animals receiving the cell-carrier sheet whereas no cells were found in animals receiving cells alone (n = 3 animals/group). We conclude that the biocompatibility and mechanical properties of the non-cross-linked collagen scaffolds make them a useful cell carrier that greatly favors tissue cell engraftment and may be exploited for cell transplantation in models of cardiac disease. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.