title: L-arginine and arginine ethyl ester enhance proliferation of endothelial cells and preadipocytes - how an arginine ethyl ester-releasing biomaterial could support endothelial cell growth in tissue engineering.
abstract: Adipose tissue engineering is a promising solution for the reconstruction of soft tissue defects. An insufficient neovascularisation within the scaffolds that leads to necrosis and tissue loss is still a major shortcoming of current tissue engineering attempts. Biomaterials, which release angiogenic factors such as L-arginine, could overcome this challenge by supporting the neovascularisation of the constructs. L-arginine is insoluble in organic solvents and thus cannot be incorporated into commonly used polymers in contrast to its ethyl ester. Here, we compared the effects of arginine and its ethyl ester on endothelial cells and preadipocytes, and generated an arginine ethyl ester-releasing, angiogenic polymer. We cultivated adipose tissue-derived endothelial cells and preadipocytes in arginine-free medium supplemented with L-arginine or L-arginine ethyl ester and assayed the proliferation rate and the degree of adipogenic differentiation, respectively. Additionally, we prepared arginine ethyl ester-releasing poly(D,L-lactide) foils, and investigated their impact on endothelial cell proliferation. We could demonstrate that arginine ethyl ester like arginine significantly increased the proliferation of endothelial cells and preadipocytes without inhibiting an induced adipogenic conversion of the preadipocytes. Further, we could show that the arginine ethyl ester-releasing polymer significantly increased endothelial cell growth. The present data are helpful guidance for generating angiogenic biomaterials that promote endothelial cell growth, and thereby could support neovascularisation within tissue engineering approaches.
authors.affiliation: Department of Plastic Surgery and Hand Surgery - Burn Center, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: N E
authors.initials: NE
authors.lastname: Paul
authors.affiliation: Department of Textile and Macromolecular Chemistry, RWTH Aachen, Aachen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Lösel
authors.affiliation: Department of Plastic Surgery and Hand Surgery - Burn Center, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hemmrich
authors.affiliation: Department of Plastic Surgery and Hand Surgery - Burn Center, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Goy
authors.affiliation: Department of Plastic Surgery and Hand Surgery - Burn Center, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Pallua
authors.affiliation: Department of Textile and Macromolecular Chemistry, RWTH Aachen, Aachen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Klee
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000328:Adult; D001120:Arginine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D001672:Biocompatible Materials / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D023822:Tissue Engineering / Q000295:instrumentation; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D001120:Arginine; C489258:arginine ethyl ester
keywords: Arginine; angiogenesis; arginine ethyl ester; endothelial cells; preadipocytes