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Replicating the extracellular matrix (ECM) is essential to mimic the composition and the architecture of native tissues or organs for tissue engineering approaches. One way to specifically replicate the cellular microenvironment is to use biomaterials derived from the decellularized ECM since they contain the entire set of proteins found in the native matrix and can provide a structural and compositional complexity for the cells. Decellularization is defined as the chemical or physical removal of all the cellular components of living tissues, creating an acellular ECM scaffold. The ECM provides mechanical support and anchoring for cells, helping to regulate and determine dynamics of cell behavior, including cell survival, proliferation, differentiation, adhesion, and migration. 1 2 3 4 If you want to know more about concepts of the ECM, its composition, role in the stem cell niche, and other important information check our E-book “Extracellular matrix: composition, organization, and regulation of stem cell behavior.”
When a tissue or organ is decellularized, it can be processed as a whole: the resident cells are washed out leaving only the ECM of the organ, and the original shape and anatomy are preserved. Although it is still a challenging approach, this decellularized organ can be recellularized with stem cells, serving as a promising platform for therapeutic applications. As a second approach, tissue-specific hydrogels can be obtained by further processing and digesting the decellularized material.5 TissueLabs MatriXpec™ hydrogels are obtained from the decellularization of more than 10 types of porcine organs and tissues and are developed to offer tissue-specific microenvironments for 3D cell culture, containing hundreds of tissue-specific extracellular matrix proteins derived from the native tissue.
Figure 1: Method for obtaining decellularized ECM-based hydrogel from tissues or organs.
Figure 2: 3D printed (FRESH method) rat heart prototype using the MatriXpec™ hydrogel developed by TissueLabs.
Liguori et al. (2020) investigated the differences between cardiovascular tissues (left ventricle, mitral valve, and aorta) on generating decellularized extracellular matrix (dECM)-based hydrogels and their interaction with cells in 2D and 3D. The left ventricle, mitral valve, and aorta of porcine hearts were decellularized using a series of detergent treatments, and the dECM was enzymatically digested to obtain hydrogels. Adipose tissue-derived stromal cells (ASCs) and human pulmonary microvascular endothelial cells were cultured in the hydrogels to analyze cellular plasticity in 2D and vascular network formation in 3D. All hydrogels supported vascular network formation within seven days of culture, but ventricular dECM hydrogel demonstrated more robust vascular networks, with thicker and longer vascular structures. 6
Figure 3: An overview of the steps involved in the obtainment of hydrogels derived from decellularized extracellular matrices 6
The work using tissue decellularization developed by Noor et al. (2019) had a massive impact on the scientific community. In this work, a biopsy of the patients' omental tissue was performed, and the cells were reprogrammed to become pluripotent stem cells and differentiated into cardiomyocytes and endothelial cells. The tissue extracellular matrix was processed into a custom hydrogel. Shortly after that, the two cell types were separately combined with hydrogels to form bioinks to print the cardiac parenchymal tissue and blood vessels. Later, as a proof of concept, a human heart prototype was 3D printed according to an anatomical model using the personalized bioinks containing appropriate cells. The results indicated the potential of the approach for engineering personalized tissues and proved the feasibility of decellularization methods. 7
Figure 4: 3D bioprinter building a personalized heart model. 8
2. Liao, J. et al. Applications of decellularized materials in tissue engineering: advantages, drawbacks and current improvements, and future perspectives. J. Mater. Chem. B Mater. Biol. Med. 8, 10023–10049 (2020).
3. Antonova, O. Y., Kochetkova, O. Y., Kanev, I. L., Shlyapnikova, E. A. & Shlyapnikov, Y. M. Rapid Generation of Neurospheres from Hippocampal Neurons Using Extracellular-Matrix-Mimetic Scaffolds. ACS Chem. Neurosci. 12, 2838–2850 (2021).
4. Grisales, P. A. et al. Chapter 14 - How the transplant landscape is changing in the regenerative medicine era. in Organ Repair and Regeneration (eds. Orlando, G. & Keshavjee, S.) 273–284 (Academic Press, 2021).
8. Freeman, D. Israeli scientists create world’s first 3D-printed heart using human cells. NBC News https://www.nbcnews.com/mach/science/israeli-scientists-create-world-s-first-3d-printed-heart-using-ncna996031 (2019).