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

Ischemic heart diseaseis one of the leading causes ofdeath worldwide.The efficient delivery of therapeutic growth factors could counteractthe adverse prognosis of post-myocardial infarction (post-MI). Inthis study, a collagen hydrogel that is able to load and appropriatelydeliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physicallycoupled with a compact collagen membrane in order to provide the suturestrength required for surgical implantation. This bilayer collagen-on-collagenscaffold (bCS) showed the suitable physicochemical properties thatare needed for efficient implantation, and the scaffold was able todeliver therapeutic growth factors after MI. In vitro collagen matrix biodegradation led to a sustained SDF1 release anda lack of cytotoxicity in the relevant cell cultures. In vivo intervention in a rat subacute MI model resulted in the full integrationof the scaffold into the heart after implantation and biocompatibilitywith the tissue, with a prevalence of anti-inflammatory and pro-angiogenicmacrophages, as well as evidence of revascularization and improvedcardiac function after 60 days. Moreover, the beneficial effect ofthe released SDF1 on heart remodeling was confirmed by a significantreduction in cardiac tissue stiffness. Our findings demonstrate thatthis multimodal scaffold is a desirable matrix that can be used asa drug delivery system and a scaffolding material to promote functionalrecovery after MI.

Automated summary

Ischemic heart disease is a major cause of death worldwide. A collagen hydrogel loaded with pro-angiogenic SDF1 was combined with a compact collagen membrane to create a bilayer collagen-on-collagen scaffold (bCS), capable of efficiently delivering therapeutic growth factors after myocardial infarction (MI). In vitro and in vivo studies demonstrated that the bCS had suitable physicochemical properties, leading to sustained release of SDF1, integration into the heart tissue, anti-inflammatory and pro-angiogenic macrophage presence, revascularization, and improved cardiac function. This multimodal scaffold can serve as a promising matrix for drug delivery and functional recovery after MI.