A Multimodal Scaffold for SDF1 Delivery Improves Cardiac Function in a Rat Subacute Myocardial Infarct Model

Perez-Estenaga, Iñigo ; Chevalier, Merari Tumin ; Peña, Estefania (Universidad de Zaragoza) ; Abizanda, Gloria ; Alsharabasy, Amir M. ; Larequi, Eduardo ; Cilla, Myriam (Universidad de Zaragoza) ; Perez, Marta M. (Universidad de Zaragoza) ; Gurtubay, Jon ; Garcia-Yebenes Castro, Manuel ; Prosper, Felipe ; Pandit, Abhay ; Pelacho, Beatriz

Resumen: Ischemic heart disease is one of the leading causes of death worldwide. The efficient delivery of therapeutic growth factors could counteract the adverse prognosis of post-myocardial infarction (post-MI). In this study, a collagen hydrogel that is able to load and appropriately deliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physically coupled with a compact collagen membrane in order to provide the suture strength required for surgical implantation. This bilayer collagen-on-collagen scaffold (bCS) showed the suitable physicochemical properties that are needed for efficient implantation, and the scaffold was able to deliver therapeutic growth factors after MI. In vitro collagen matrix biodegradation led to a sustained SDF1 release and a lack of cytotoxicity in the relevant cell cultures. In vivo intervention in a rat subacute MI model resulted in the full integration of the scaffold into the heart after implantation and biocompatibility with the tissue, with a prevalence of anti-inflammatory and pro-angiogenic macrophages, as well as evidence of revascularization and improved cardiac function after 60 days. Moreover, the beneficial effect of the released SDF1 on heart remodeling was confirmed by a significant reduction in cardiac tissue stiffness. Our findings demonstrate that this multimodal scaffold is a desirable matrix that can be used as a drug delivery system and a scaffolding material to promote functional recovery after MI.

Idioma: Inglés

DOI: 10.1021/acsami.3c04245

Año: 2023

Publicado en: ACS applied materials & interfaces 15, 44 (2023), 50638-50651
ISSN: 1944-8244

Factor impacto SCIMAGO: 2.058 - Materials Science (miscellaneous) (Q1) - Nanoscience and Nanotechnology (Q1) - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/EC/H2020/713690/EU/Career Development and Mobility Fellowships in Medical Device Research and Development: A CÚRAM Industry-Academia Training Initiative/MedTrain
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/AC15-00050
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FEDER/RD16-0011-0005
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI19-00501
Financiación: info:eu-repo/grantAgreement/ES/MICIU/RTC-2016-4911-1
Financiación: info:eu-repo/grantAgreement/EUR/SUDOE/INTERREG CARDIOPATCH-SOE4-P1-E1063

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Anatom.Anatom.Patológ.Com (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)