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

Araña, M. ; Peña, E. (Universidad de Zaragoza) ; Abizanda, G. ; Cilla, M. (Universidad de Zaragoza) ; Ochoa, I. (Universidad de Zaragoza) ; Gavira, J. J. ; Espinosa, G. ; Doblaré, M. (Universidad de Zaragoza) ; Pelacho, B. ; Prosper, F.

Resumen: 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 × 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 × 103 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 × 1.2 cm size collagen scaffolds implanted onto the heart 1 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: 16.3 ± 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.

Idioma: Inglés

DOI: 10.1016/j.actbio.2012.12.014

Año: 2013

Publicado en: ACTA BIOMATERIALIA 9, 4 (2013), 6075-6083
ISSN: 1742-7061

Factor impacto JCR: 5.684 (2013)

Categ. JCR: MATERIALS SCIENCE, BIOMATERIALS rank: 3 / 29 = 0.103 (2013) - Q1 - T1
Categ. JCR: ENGINEERING, BIOMEDICAL rank: 3 / 75 = 0.04 (2013) - Q1 - T1

Tipo y forma: Article (PostPrint)

Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)