Written by Jamie Saito ‘25
Edited by Surya Khatri '24
Calcium in Cell-Extracellular Matrix Interactions.
A new biomaterial developed at the University of California San Diego may change emergency care treatment. Researchers have created a new material that can be delivered intravenously to induce tissue repair. This non-invasive procedure has the potential to be applied in high-acuity settings, such as heart attacks, traumatic brain injuries, and pulmonary hypertension.
Previous biomaterial research has focused on the extracellular matrix (ECM), which serves as a biological scaffold for cells. Previous research has studied whether these naturally occurring structures could serve as therapeutic devices, inducing and promoting growth of new cells in damaged tissues . Since the ECM is a complex network, consisting of many different proteins and growth factors, it cannot be easily created in a laboratory. Instead, harvest these scaffolds from preexisting tissues by removing cells and maintaining the structural integrity of the matrix. At the University of California lab, researchers decellularized tissues to isolate the ECM and developed an injectable hydrogel for easier delivery . However, the applications of this product are limited because hydrogels need to be surgically implanted, which is an invasive procedure not conducive for high-acuity situations .
To tackle this problem, researchers decided to manipulate how they preserved the ECM. Instead of turning it into a hydrogel, they centrifuged and filtered the liquid precursor, isolating nano-sized particles . They then sterilized and freeze-dried the remaining material, turning it into a powder. The researchers could then add sterile water to the powder ECM, turning it into a liquid that can be delivered intravenously . To study the safety of this product, researchers ensured that this new ECM material did not induce blood clots and functioned within physiological range . This was critical to ensure that the material can be applied safely in humans and not cause adverse effects.
Using three animal models of a heart attack, traumatic brain injury, and pulmonary hypertension, the researchers studied how effective this gel was at repairing damaged tissues. Importantly, they found that the therapeutic material localized to the targeted treatment areas . For example, in the heart attack model, ECM was present in the myocardial tissue damaged by the heart attack with limited presence in other areas of the heart. This suggests that the ECM may be used to target areas of damage, showing practical adaptability to a range of applications.
Results from this study suggest that leaky vasculature is a key component in this therapeutic approach. In a chronic heart attack animal model, where there is no leaky vasculature, the material did not localize to the area of damage and therefore was unable to repair the cells . ECM material appeared to work by filling in the gaps between endothelial cells, which accelerated the repair of blood vessels. It also appeared to reduce the inflammatory response. Together, these findings suggest that the ECM material promotes vascularization and therefore increases cell survival . This is important for applications such as heart attacks, where myocardial cells begin to die due to a lack of oxygen and nutrients provided by blood vessels. By promoting growth of the vessels, the cells may be able to maintain physiological function, leading to decreased damage to the heart.
The University of California lab hopes to move toward preclinical stages and further investigate the safety of this new material. Though there are still many steps to complete before this ECM material may be seen in a clinical setting, these initial results show promise for the future of emergency therapeutic procedures.
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 Spang MT, Middleton R, Diaz M, Hunter J, Mesfin J, Banka A, et al. Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues. Nat Biomed Eng. 2022 Dec 29;1–16.
 This groundbreaking biomaterial heals tissues from the inside out: The material can be injected intravenously and has potential application in heart attacks, traumatic brain injury and more [Internet]. ScienceDaily. [cited 2023 Mar 6]. Available from: https://www.sciencedaily.com/releases/2023/01/230130144805.htm