Abstract 195: Engineering Shear-thinning Injectable Biomimetic Hydrogel to Repair Damaged Cardiac Tissue

Abstract

Rationale: In acute myocardial infarction (AMI), prognosis and mortality rate are closely related to the infarct size and the progression of post-infarction cardiac failure. Delivery of stem cell derived secretome (miR, growth factor, exosome) has presented a new approach for the treatment of AMI. However, protection of bioactivity of delivered secretome and its retention at target site remains a challenge that can lead to sub-optimal results. Methods and Results: Here, we present a shear-thinning nanocomposite tissue adhesive hydrogels composed of synthetic 2% silicate nanoplatelets and 5% gelatin as injectable platform for effectively deliver adipose stem cell-derived secretome. This nanogel forms a highly crosslinked gel which could sustain high strain and recover its original stiffness once the strain is removed. This property is essential to prevent the material from flowing out of the therapeutic site once injected and thus enabling longer retention of the secretome. We used a novel microfluidic technology to harness high concentration secretome from stem cell spheroids before loading it to the hydrogel. The hydrogel-secretome (HS) demonstrated significantly enhanced in vitro angiogenic activity and cardioprotection. We hypothesized that the HS might promote angiogenesis cooperatively with the delivered secretome. To evaluate our hypothesis, we employed a rat AMI model and injectable HS gel to the heart. A significant increase in capillary density and reduction in infarct sizes were noted in the infarcted hearts with HS treatment compared with ctrl infarcted hearts treated with saline, hydrogel or secretome only groups. Furthermore, the HS showed significantly higher cardiac performance in echocardiography (62.8±3 of ejection fraction vs 45.2±5 ctrl, P < 0.05, n=6) 3 weeks post MI. In combination with bioprinting and microscale technologies, we have also sucessfully fabricated an elastomeric scaffold with this HS gel that can be used as a cardiac patch. Conclusion: The combination of injectability, rapid mechanical recovery, cargo retention ability, bioprintability and ability to attenuate progression of cardiac dysfunction makes this HS gel a versatile platform for cardiac biotherapeutics and tissue engineering applications.