Decellularization of porcine heart tissue to obtain extracellular matrix based hydrogels

Sakina, Rabeil; Llucià‐Valldeperas, Aida; Lourenço, Ana Henriques; Harichandan, Abhishek; Gelsomino, Sandro; Wieringa, Paul; Mota, Carlos; Moroni, Lorenzo

doi:10.1016/bs.mcb.2019.11.023

Cited by 7 publications

(12 citation statements)

References 48 publications

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“…The balance between cell removal and ECM preservation, efficient recellularization with new cells of dECM for obtaining homogenous cell distribution are to be optimized to use for bioprinting applications 72‐75 . These concerns include notable scaffold elicited immunogenicity due to the presence of extraneous proteins and sugars, and toxicity due to decellularization chemicals are to be addressed 76‐81 …”

Section: Bioinksmentioning

confidence: 99%

Progress in cardiovascular bioprinting

Quadri

Soman²,

Vijayavenkataraman

2021

Artificial Organs

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Cardiovascular disease has been the leading cause of death globally for the past 15 years. Following a major cardiac disease episode, the ideal treatment would be the replacement of the damaged tissue, due to the limited regenerative capacity of cardiac tissues. However, we suffer from a chronic organ donor shortage which causes approximately 20 people to die each day waiting to receive an organ. Bioprinting of tissues and organs can potentially alleviate this burden by fabricating low cost tissue and organ replacements for cardiac patients. Clinical adoption of bioprinting in cardiovascular medicine is currently limited by the lack of systematic demonstration of its effectiveness, high costs, and the complexity of the workflow. Here, we give a concise review of progress in cardiovascular bioprinting and its components. We further discuss the challenges and future prospects of cardiovascular bioprinting in clinical applications.

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Section: Bioinksmentioning

confidence: 99%

Progress in cardiovascular bioprinting

Quadri

Soman²,

Vijayavenkataraman

2021

Artificial Organs

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“…Likewise, advancements in tissuespecific 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. 17 These biomaterials exhibit limited control over mechanical properties and high degradation rates that make it difficult to recapitulate the fibrotic microenvironment in vitro.…”

Section: ■ Introductionmentioning

confidence: 99%

Chemical Modification of Human Decellularized Extracellular Matrix for Incorporation into Phototunable Hybrid-Hydrogel Models of Tissue Fibrosis

Hewawasam

Blomberg

Šerbedžija

et al. 2023

ACS Appl. Mater. Interfaces

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Tissue fibrosis remains a serious health condition with high morbidity and mortality rates. There is a critical need to engineer model systems that better recapitulate the spatial and temporal changes in the fibrotic extracellular microenvironment and enable study of the cellular and molecular alterations that occur during pathogenesis. Here, we present a process for chemically modifying human decellularized extracellular matrix (dECM) and incorporating it into a dynamically tunable hybrid-hydrogel system containing a poly(ethylene glycol)-α methacrylate (PEGαMA) backbone. Following modification and characterization, an off-stoichiometry thiol-ene Michael addition reaction resulted in hybrid-hydrogels with mechanical properties that could be tuned to recapitulate many healthy tissue types. Next, photoinitiated, free-radical homopolymerization of excess α-methacrylates increased crosslinking density and hybrid-hydrogel elastic modulus to mimic a fibrotic microenvironment. The incorporation of dECM into the PEGαMA hydrogel decreased the elastic modulus and, relative to fully synthetic hydrogels, increased the swelling ratio, the average molecular weight between crosslinks, and the mesh size of hybrid-hydrogel networks. These changes were proportional to the amount of dECM incorporated into the network. Dynamic stiffening increased the elastic modulus and decreased the swelling ratio, average molecular weight between crosslinks, and the mesh size of hybrid-hydrogels, as expected. Stiffening also activated human fibroblasts, as measured by increases in average cellular aspect ratio (1.59 ± 0.02 to 2.98 ± 0.20) and expression of α-smooth muscle actin (αSMA). Fibroblasts expressing αSMA increased from 25.8 to 49.1% upon dynamic stiffening, demonstrating that hybrid-hydrogels containing human dECM support investigation of dynamic mechanosensing. These results improve our understanding of the biomolecular networks formed within hybrid-hydrogels: this fully human phototunable hybrid-hydrogel system will enable researchers to control and decouple the biochemical changes that occur during fibrotic pathogenesis from the resulting increases in stiffness to study the dynamic cell–matrix interactions that perpetuate fibrotic diseases.

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“…17 These biomaterials exhibit limited control over mechanical properties and high degradation rates that make it difficult recapitulate the fibrotic microenvironment in vitro. [18][19][20][21] One approach to maintain ECM ligands for cellular binding and long-term culture, while enabling mechanical tunability, is chemical modification of natural materials. For example, methacrylation of gelatin and hyaluronic acid resulted in scaffolds that maintained encapsulated valvular interstitial cells (myofibroblast precursors from the heart valve leaflet) for several weeks in culture in a quiescent state.…”

Section: Introductionmentioning

confidence: 99%

“…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. 17 These biomaterials exhibit limited control over mechanical properties and high degradation rates that make it difficult recapitulate the fibrotic microenvironment in vitro .…”

Section: Introductionmentioning

confidence: 99%

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

Hewawasam

Šerbedžija

Blomberg

et al. 2022

Preprint

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Tissue fibrosis remains a serious health condition with high morbidity and mortality rates. There is a critical need to engineer model systems that better recapitulate the spatial and temporal changes in the fibrotic extracellular microenvironment and enable study of the cellular and molecular alterations that occur during pathogenesis. Here, we present a process for chemically modifying human decellularized extracellular matrix (dECM) and incorporating it into a dynamically tunable hybrid-hydrogel system containing a poly(ethylene glycol)-alpha methacrylate (PEGαMA) backbone. Following modification and characterization, an off-stoichiometry thiol-ene Michael addition reaction resulted in hybrid-hydrogels with mechanical properties that could be tuned to recapitulate many healthy tissue types. Next, photoinitiated, free-radical homopolymerization of excess α-methacrylates increased crosslinking density and hybrid-hydrogel elastic modulus to mimic a fibrotic microenvironment. The incorporation of dECM into the PEGαMA hydrogel decreased the elastic modulus and, relative to fully synthetic hydrogels, increased the swelling ratio, the average molecular weight between crosslinks, and the mesh size of hybrid-hydrogel networks. These changes were proportional to the amount of dECM incorporated into the network. Dynamic stiffening increased the elastic modulus and decreased the swelling ratio, average molecular weight between crosslinks, and the mesh size of hybrid-hydrogels, as expected. Stiffening also activated human fibroblasts, as measured by increases in average cellular aspect ratio (1.59 ± 0.02 to 2.98 ± 0.20) and expression of α-smooth muscle actin (αSMA). Fibroblasts expressing αSMA increased from 24.4% to 51.8% upon dynamic stiffening, demonstrating that hybrid-hydrogels containing human dECM support investigation of dynamic mechanosensing. These results improve our understanding of the biomolecular networks formed within hybrid-hydrogels: this fully human phototunable hybrid-hydrogel system will enable researchers to control and decouple the biochemical changes that occur during fibrotic pathogenesis from the resulting increases in stiffness to study the dynamic cell-matrix interactions that perpetuate fibrotic diseases.

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Decellularization of porcine heart tissue to obtain extracellular matrix based hydrogels

Cited by 7 publications

References 48 publications

Progress in cardiovascular bioprinting

Progress in cardiovascular bioprinting

Chemical Modification of Human Decellularized Extracellular Matrix for Incorporation into Phototunable Hybrid-Hydrogel Models of Tissue Fibrosis

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

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