Clickable decellularized extracellular matrix as a new tool for building hybrid-hydrogels to model chronic fibrotic diseases in vitro

Abstract

Hydrolytically stable, phototunable hybrid-hydrogels containing clickable decellularized extracellular matrix enable spatiotemporal control over fibroblast activation.

Decellularised scaffolds: just a framework? Current knowledge and future directions

“…These cell-containing hydrogels can then be injected for minimally invasive delivery into irregular spaces, [68][69][70] applied topically or used for 3D printing or electrospinning. 57,71 Some of the medical conditions for which decellularised ECM-based hydrogels have been investigated include type 1 diabetes, 70 myocardial infarction by replacing damaged cardiac tissue, 68,69 peripheral artery disease, 72 skin wound healing, 73 keratoconus by bioprinting a corneal stromal substitute, 71 acute liver failure, 74 chronic fibrotic diseases 75 and inflammatory bowel disease. 76 The impact of the decellularisation method on the ECM-derived hydrogel has been shown by several studies.…”

“…Since decellularised tissues possess the native ECM components and structure, they could be of great value in applications that require 3D ex vivo platforms, such as disease modelling to study their progression and new targets, as well as screening and investigation of drugs/ therapeutics. 75,76,94 Such application can be very relevant in cancer, where the biological activity of cancerous cells is not only affected by physicochemical changes in the ECM, but also they can alter the ECM by, for example, applying mechanical forces for expansion or by secreting enzymes that promote cancer spread. A tumour comprises a microenvironment that undergoes remodelling following extracellular, intercellular and intracellular signals.…”

“…Since decellularised tissues possess the native ECM components and structure, they could be of great value in applications that require 3D ex vivo platforms, such as disease modelling to study their progression and new targets, as well as screening and investigation of drugs/therapeutics. 75 , 76 , 94 …”

Engineering Tissue-Informed Biomaterials to Advance Pulmonary Regenerative Medicine

“…In a recent example of pulmonary disease modeling, a dynamically responsive PEG-α-methacrylate (PEGαMA) hybrid-hydrogel containing proteins from decellularized lung extracellular matrix was stiffened in situ using light to increase the elastic modulus of the material from healthy (E = 3.6 ± 0.24 kPa) to fibrotic ranges (E = 13.4 ± 0.82 kPa). These stiffened hydrogels induced a significant increase in the expression of myofibroblast transgenes within primary murine fibroblasts (80). Likewise, Lewis et al exploited photodegradable PEGbased hydrogel microspheres to template lung epithelial cells within a biomaterial platform to create open cyst-like structures (81).…”

“…In fibrotic diseases such as idiopathic pulmonary fibrosis and pulmonary arterial hypertension, an aberrant healing response and excess collagen deposition lead to increases in lung stiffness from 1-5 kPa (healthy) to over 10 kPa (fibrotic) (84,85), while COPD results in an overall decrease in tissue organization and stiffness (85). Biomaterials mimicking these dynamic changes in extracellular matrix mechanics could be readily designed to provide sophisticated in vitro models of patient-specific disease and treatment (80,86). Currently, the strength of tissue-informed biomaterials has not been harnessed in pulmonary medicine, but the opportunities are substantial and should continue to be investigated in the future.…”