TY - JOUR

T1 - Vascular Network Formation on Macroporous Polydioxanone Scaffolds

AU - Heene, Sebastian

AU - Thoms, Stefanie

AU - Kalies, Stefan

AU - Wegner, Nils

AU - Peppermüller, Pia

AU - Born, Nikolai

AU - Walther, Frank

AU - Scheper, Thomas

AU - Blume, Cornelia A

N1 - Funding Information: This study was funded by the Deutsche Forschungs-gemeinschaft (DFG;Grant No. 388094931). This work has further been carried out within the framework of the SMART BIOTECS alliance between the Technische Universitaet Braunschweig and the Leibniz Universitaet Hannover. This initiative is supported by the Ministry of Economy and Culture (MWK) of Lower Saxony, Germany.

PY - 2021/10/18

Y1 - 2021/10/18

N2 - In this study, microvascular network structures for tissue engineering were generated on newly developed macroporous polydioxanone (PDO) scaffolds. PDO represents a polymer biodegradable within months and offers optimal material properties such as elasticity and nontoxic degradation products. PDO scaffolds prepared by porogen leaching and cryo-dried to achieve pore sizes of 326 ± 149.67 μm remained stable with equivalent values for Young's modulus after 4 weeks. Scaffolds were coated with fibrin for optimal cell adherence. To exclude interindividual differences, autologous fibrin was prepared out of human plasma-derived fibrinogen and proved a comparable quality to nonautologous commercially available fibrinogen. Fibrin-coated scaffolds were seeded with recombinant human umbilical vein endothelial cells expressing GFP (GFP-HUVECs) in coculture with adipose tissue-derived mesenchymal stem cells (AD-hMSCs) to form vascular networks. The growth factor content in culture media was optimized according its effect on network formation, quantified and assessed by AngioTool®. A ratio of 2:3 GFP-HUVECs/AD-hMSCs in medium enriched with 20 ng/mL vascular endothelial growth factor, basic fibroblast growth factor, and hydrocortisone was found to be optimal. Network structures appeared after 2 days of cultivation and stabilized until day 7. The resulting networks were lumenized that could be verified by dextran staining. This new approach might be suitable for microvascular tissue patches as a useful template to be used in diverse vascularized tissue constructs.

AB - In this study, microvascular network structures for tissue engineering were generated on newly developed macroporous polydioxanone (PDO) scaffolds. PDO represents a polymer biodegradable within months and offers optimal material properties such as elasticity and nontoxic degradation products. PDO scaffolds prepared by porogen leaching and cryo-dried to achieve pore sizes of 326 ± 149.67 μm remained stable with equivalent values for Young's modulus after 4 weeks. Scaffolds were coated with fibrin for optimal cell adherence. To exclude interindividual differences, autologous fibrin was prepared out of human plasma-derived fibrinogen and proved a comparable quality to nonautologous commercially available fibrinogen. Fibrin-coated scaffolds were seeded with recombinant human umbilical vein endothelial cells expressing GFP (GFP-HUVECs) in coculture with adipose tissue-derived mesenchymal stem cells (AD-hMSCs) to form vascular networks. The growth factor content in culture media was optimized according its effect on network formation, quantified and assessed by AngioTool®. A ratio of 2:3 GFP-HUVECs/AD-hMSCs in medium enriched with 20 ng/mL vascular endothelial growth factor, basic fibroblast growth factor, and hydrocortisone was found to be optimal. Network structures appeared after 2 days of cultivation and stabilized until day 7. The resulting networks were lumenized that could be verified by dextran staining. This new approach might be suitable for microvascular tissue patches as a useful template to be used in diverse vascularized tissue constructs.

KW - angiogenesis

KW - fibrin

KW - polydioxanone

KW - scaffolds

KW - vascular networks

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=85118245902&partnerID=8YFLogxK

U2 - 10.1089/ten.TEA.2020.0232

DO - 10.1089/ten.TEA.2020.0232

M3 - Article

C2 - 33397206

VL - 27

SP - 1239

EP - 1249

JO - Tissue Engineering - Part A

JF - Tissue Engineering - Part A

SN - 1937-3341

IS - 19-20

ER -