In heart attacks, the heart muscle tissue that has lost its blood supply is severely injured, leading to major cell death – notably of cardiomyocytes. Wound healing responses drive the formation of fibrous scar tissue to replace the lost muscle. This cardiac fibrosis can lead to heart failure, which affects over 26 million adults worldwide and contributes to 1 in 8 deaths in the United States. Currently no effective clinical treatments exist to reduce and reverse the formation of excess scar tissue.
We are developing new strategies for cardiac engineering with the goal of reducing pathological fibrosis, promoting cardiomyocyte growth, and revascularizing the infarct area. We have developed 2D micropeg and 3D microrod scaffold systems that significantly inhibit proliferation of fibroblasts and the synthesis of extracellular matrix proteins.
Current and Future Work:
- Understanding the biochemical and biophysical response of fibroblasts to microrods
- Exploring the use of microrods as a drug delivery device to inhibit fibrosis or promote vascularization
- Identifying the influence microrods have on the innate immune response following heart attack
(A) Hyaluronic acid microrods (HAMRs) were fabricated by exposure of a thin film of HA methacrylate to UV light through a photomask. (B) Primary cardiac fibroblasts are observed conforming to HAMR geometry via focal adhesions. (C) NIH-3T3 fibroblasts exhibit reduced expression of αSMA, Col1A2, TGFb, and MMP2 when cultured with HAMRs in 3D Matrigel. (D) Rats treated with HA microrods have significantly higher change from baseline ejection fraction than saline or HA solution groups as measured by echocardiography 6 weeks after injection. Data presented as mean ± SD.
Recent Publications: Le LV, Mohindra P, et al (2018). Biomaterials.
Point(s) of Contact: Priya Mohindra, Justin Zhong
In collaboration with Randall Lee, MD, PhD.