Nanofibrous cardiac patch containing decellularized Wharton's jelly matrix promotes cardiac repair in infarcted rats

Abstract

During myocardial infarction (MI), the progressive death of cardiomyocytes and subsequent loss of tissue extracellular matrix leads to drastic alterations in the structure and mechanical performance of the heart, thereby leading to cardiac failure. Passive epicatrial therapy, with a cardiac patch, works by physically curbing the infarcted zone to inhibit infarct expansion, while simultaneously inducing cardiac regeneration. However, its functionality has restricted due to intricacy of cardiac tissue which exhibited a special micro/nano fibrous matrix containing crucial mediators in developing and modulating cell metabolism. To address these issues, we introduced a durable nanofibrous cardiac patch containing decellularized Wharton's jelly extracellular matrix (DWJM), which has proven to be an ideal bioactive potential material that provides a cohesive patch with essential signals for directing cell growth and differentiation. Nanofibrous scaffolds with different proportions of poly lactic acid (PLA) and DWJM were fabricated by electrospinning. In vitro experiments were conducted to characterize the scaffolds in terms of their physical, mechanical, and cytocompatibility. Optimized scaffolds were transplanted into an MI rat model for MI treatment. A well-organized and defect-free nanofibrous membrane with randomly oriented fibers was obtained with a DWJM proportion in a range of 25 % (PLA 75: DWJM25). The hydrophobicity of the PLA nanofibrous membrane and the poor mechanical strength of the DWJM membrane were improved by co-electrospinning, and durable and reinforced nanofibers were generated in PLA 75: DWJM25. Scaffolds seeded with H9c2 cells and human umbilical cord mesenchymal stem cells (HUC-MSCs) revealed that PLA75: DWJM25 presented excellent cell viability and biocompatibility compared with PLA. On day 28 post-transplantation in the MI rat models, PLA75: DWJM25 reduced infarct size and improved cardiac function. Additionally, obvious neovascularization was observed. Results suggested that the transplantation of a cardiac patch composed of DWJM and PLA could serve as a potential therapeutic candidate for MI repair.