scholarly journals Minimally invasive delivery of therapeutic agents by hydrogel injection into the pericardial cavity for cardiac repair

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dashuai Zhu ◽  
Zhenhua Li ◽  
Ke Huang ◽  
Thomas G. Caranasos ◽  
Joseph S. Rossi ◽  
...  

AbstractCardiac patches are an effective way to deliver therapeutics to the heart. However, such procedures are normally invasive and difficult to perform. Here, we develop and test a method to utilize the pericardial cavity as a natural “mold” for in situ cardiac patch formation after intrapericardial injection of therapeutics in biocompatible hydrogels. In rodent models of myocardial infarction, we demonstrate that intrapericardial injection is an effective and safe method to deliver hydrogels containing induced pluripotent stem cells-derived cardiac progenitor cells or mesenchymal stem cells-derived exosomes. After injection, the hydrogels form a cardiac patch-like structure in the pericardial cavity, mitigating immune response and increasing the cardiac retention of the therapeutics. With robust cardiovascular repair and stimulation of epicardium-derived cells, the delivered therapeutics mitigate cardiac remodeling and improve cardiac functions post myocardial infarction. Furthermore, we demonstrate the feasibility of minimally-invasive intrapericardial injection in a clinically-relevant porcine model. Collectively, our study establishes intrapericardial injection as a safe and effective method to deliver therapeutic-bearing hydrogels to the heart for cardiac repair.

2021 ◽  
Vol 22 (3) ◽  
pp. 1449
Author(s):  
Woo-Sup Sim ◽  
Bong-Woo Park ◽  
Kiwon Ban ◽  
Hun-Jun Park

Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts.


Author(s):  
Hossein Amirjamshidi ◽  
Jude S. Sauer ◽  
Bryan Barrus ◽  
Peter A. Knight ◽  
Sunil M. Prasad

Objective Bilateral internal thoracic artery (BITA) bypass can enable more complete arterial revascularization procedures. Minimally invasive cardiac surgery (MICS) can offer significant patient benefits. New minimally invasive technology for sternal retraction and tissue manipulation is needed to enable ergonomic and reliable minimally invasive ITA harvesting. The goal of this research was to develop technology and techniques, along with experimental testing and training models, for a sternal-sparing approach to in situ BITA harvesting through a small subxiphoid access site. Methods This study focused on optimizing custom equipment and methods for subxiphoid BITA harvesting initially in a porcine model (19 pig carcasses, 36 ITAs) and subsequently in 7 cadavers (14 ITAs). Results Fifty consecutive ITAs were successfully harvested using this remote access approach. The last 20 ITA specimens harvested from the porcine model were explanted and measured; the average length of the free ITA grafts was 12.8 ± 0.9 cm (range 10.8 to 14.2 cm) with a mean time of 23.3 ± 5.2 minutes (range 13 to 25 minutes) for each harvest. Conclusions Early results demonstrate that both ITAs can be reliably harvested in a skeletonized fashion in situ through sternal-sparing, small subxiphoid access in 2 experimental models. This innovative approach warrants further exploration toward facilitating complete arterial revascularization and the further adoption of minimally invasive coronary artery bypass graft surgery.


2012 ◽  
Vol 16 (11) ◽  
pp. 2549-2563 ◽  
Author(s):  
Zhuzhi Wen ◽  
Zun Mai ◽  
Haifeng Zhang ◽  
Yangxin Chen ◽  
Dengfeng Geng ◽  
...  

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