An in vitro model of fibrosis using crosslinked native extracellular matrix-derived hydrogels to modulate biomechanics without changing composition

Chemical modification of human decellularized extracellular matrix for incorporation into phototunable hybrid-hydrogel models of tissue fibrosis

“…65–67,26 In particular, Nizamoglu et al created hydrogels from porcine dECM that could be stiffened by using a ruthenium and sodium persulfate-initiated reaction to crosslink tyrosine moieties on the dECM. Results of fibroblast activation studies using this model showed increased activation induced by stiffening, even when the dECM composition of the hydrogel remained the same 66 . Similarly, murine fibroblasts cultured on PEG-based hybrid-hydrogels consisting of porcine dECM 25 and murine dECM 26 showed prominent Col1a1 and αSMA expression on stiffened hydrogels.…”

“…64 However, recent studies using models designed to decouple fibrotic composition from mechanical stress showed that material stiffness is the dominant factor that affects the activation of fibroblasts. [65][66][67]26 In particular, Nizamoglu et al created hydrogels from porcine dECM that could be stiffened by using a ruthenium and sodium persulfate-initiated reaction to crosslink tyrosine moieties on the dECM.…”

“…22,23 To decouple the changes in ECM composition from subsequent mechanical changes, Nizamoglu et al reported a strategy for tailoring the mechanical properties of human lung dECM hydrogels using ruthenium/sodium persulfate-initiated di-tyrosine crosslinking in a way that does not alter the chemical composition. 24 Similarly, Petrou et al and Saleh et al engineered hybrid-hydrogel systems that employed a phototunable PEGαMA backbone as a blank slate for the addition of healthy porcine lung dECM or healthy and fibrotic murine lung dECM, respectively, and showed that dynamic stiffening in situ increased fibroblast activation in real-time. 25,26 Here we build on this work by chemically modifying human dECM for incorporation into a dual-stage polymerization hybrid-hydrogel system and characterizing the resulting hydrogel networks.…”

“…5 Naturally derived hydrogel biomaterials, including Matrigel, 6–8 fibrin, 9, 10 and collagen 11–13 , have been used extensively to study fibrosis in lung, liver, skin, and muscle. Likewise, advancements in tissue-specific decellularization have resulted in dECM hydrogels, which can model disease progression in lung, 14 liver 15 , and heart. 16 Although these biomaterials offer environments rich in endogenous biochemical cues, natural polymers that form structures through self-assembly present engineering challenges.…”

Highway to heal: Influence of altered extracellular matrix on infiltrating immune cells during acute and chronic lung diseases

“…These include synthetic polymers such as poly (ethylene glycol) ( Widener et al, 2021 ) and natural polymers such as collagen ( Li et al, 2018 ; Surendran et al, 2021 ). Methodologies including precision cut lung slices (PCLS), organoids, lung-on-chip, whole decellularized lung tissues, and hydrogels have been developed over the past decades to mimic physiological environments in vitro , each with their own advantages and challenges ( Gkatzis et al, 2018 ; Liu et al, 2019 ; Nizamoglu et al, 2022 ). However, there has been limited implementation of such models for studying immune cell infiltration, thereby providing future opportunities for exploring the dynamics between ECM and infiltrating immune cell migration in the context of lung diseases.…”