Biology subjects

Cabrales, P.

Publications and source records attributed to Cabrales, P..

3 recordsLinked to original sources

bioRxiv2026

An Improved Manufacturing Method for Infusible Extracellular Matrix Materials to Enable Efficient Scale-Up, Improved Efficacy, and Clinical Translation

Decellularized extracellular matrix (ECM) materials are a popular choice for tissue engineering and regenerative medicine applications due to their multifaceted bioactive capabilities arising from their heterogenous composition. For minimally invasive delivery, infusible ECM (iECM) was developed through fractionation of digested decellularized ECM, allowing the material to be safely delivered intravascularly. iECM localizes to permeable vasculature in inflamed tissues and exerts immunomodulatory and pro-reparative effects with proof-of-concept already demonstrated in multiple preclinical models including myocardial infarction (MI) and multiple organ dysfunction syndrome (MODS). However, one major limitation of iECM is the steps required for manufacturing, involving centrifugation, dialysis/lyophilization, and filtration (C-D-F). These steps limit manufacturing output and iECM concentration, and require significant human handling, limiting compliance with current good manufacturing practices (cGMP). To overcome these challenges, we developed a method for manufacturing iECM that utilizes depth filtration and tangential flow filtration (DF-TFF), which reduces manufacturing time, allows for increased iECM concentration, and reduces human manipulation of material, improving translatability and scalability of iECM materials. Based on multiple material characterization methods, we determined that iECM made with DF-TFF was comparable to iECM made with C-D-F. By increasing iECM concentration through this manufacturing method, we demonstrate a dose dependent response in an acute MI porcine model and a mouse MODS model. Finally, DF-TFF enabled timely production of iECM from alternative tissue sources. Altogether, DF-TFF allows for improvements in production time, scale-up, cGMP compliance, and increased dose through higher concentration, paving the way for future clinical translation as well new preclinical studies.

bioengineering↗

bioRxiv2025

In vivo itaconate tracing reveals degradation pathway and turnover kinetics

Itaconate is an immunomodulatory metabolite that alters mitochondrial metabolism and immune cell function. This organic acid is endogenously synthesized via tricarboxylic acid (TCA) metabolism downstream of TLR signaling. Itaconate-based treatment strategies are being explored to mitigate numerous inflammatory conditions. However, little is known about the turnover rate of itaconate in circulation, the kinetics of its degradation, and the broader consequences on metabolism. By combining mass spectrometry and in vivo 13C itaconate tracing, we demonstrate that itaconate is rapidly eliminated from plasma, excreted via urine, and fuels TCA cycle metabolism specifically in the liver and kidneys. These studies further revealed that itaconate is converted into acetyl-CoA, mesaconate, and citramalate in mitochondria. Itaconate administration also influenced branched-chain amino acid metabolism and succinate levels, indicating a functional impact on succinate dehydrogenase (SDH) and methylmalonyl-CoA mutase (MUT) activity. Our findings uncovered a previously unknown aspect of the itaconate metabolism, highlighting its rapid catabolism in vivo that contrasts findings in cultured cells.

cell biology↗

bioRxiv2020

A New Form of Decellularized Extracellular Matrix Hydrogel for Treating Ischemic Tissue via Intravascular Infusion

Biomaterials, such as extracellular matrix (ECM) hydrogels, have been widely used in preclinical studies as injectable tissue engineering therapies; however, injectable therapies are limited as they can cause localized trauma or organ perforation. We have developed a new ECM therapy, the low molecular weight fraction derived from decellularized, digested ECM, for intravascular infusion. This new form of ECM can be infused after injury, specifically localize to injured tissues by coating the leaky microvasculature, and promote cell survival and tissue repair. In this study, we show the feasibility and targeting of intravascular ECM infusions using models of acute myocardial infarction (MI), traumatic brain injury, and pulmonary arterial hypertension. Furthermore, safety and efficacy were demonstrated in small and large animal models of acute MI following intracoronary infusion, which included using a clinically-relevant catheter in the large animal model. Functional improvements, specifically reduced left ventricular volumes and improved wall motion scores were observed after ECM infusions post-MI. Genes related to tissue repair and inflammation were differential expressed in response to ECM infusions. This study shows proof-of-concept for a new paradigm of delivering pro-healing ECM biomaterials via intravascular infusion to heal tissue from the inside out.

bioengineering↗