In a recent article published in the journal Biomaterialsresearchers examined the challenges, synthetic techniques, and advances in developing decellularized extracellular matrix (dECM)-based biomaterials to mimic the specific physical and biological characteristics of native tissues.
Study: Decellularized extracellular matrix: Promising and stimulating new biomaterials for regenerative medicine. Image Credit: picmedical/Shutterstock.com
The native tissue group is composed of various cell types accompanied by an extracellular matrix (ECM). The ECM serves as a support and structural network, including a source of extracellular signaling molecules for resident cells. The ability to accurately recreate the physicochemical characteristics, or complex physical and biological attributes, of the native ECM for fully functional tissue recovery in regenerative medicine, has been a critical challenge in tissue engineering (TE).
By providing a microenvironment similar to native tissue, biomaterials made from dECM can support specialized cell types and trigger their inherent regeneration process. dECM sheets were originally intended for the complete regeneration and replacement of tissues or organs. Decellularization, on the other hand, can significantly reduce the mechanical properties and structural stability of all dECM sheets. In this study, more than 300 original research papers covering dECM particle-based biomaterials published in peer-reviewed publications from January 2012 to December 2021 were reviewed by the team.
Advances in Major Tissue Types in dECM TE
Cardiac TE aims to improve stem cell viability and retention by delivering vascularized, biodegradable patches with the conductivity, contractility, and elasticity of cardiac muscle to mimic the native cardiomyocyte (CM) niche. Heart-specific dECM biomaterials were designed to mimic cardiac mechanics while providing signals at key time points for stem cell differentiation into CM and efficient cardiac tissue repair. dECM cardiac biomaterials can extend beyond cardiac hydrogels and patches to function as a provisional stent for vessel restoration.
In addition, TE cartilage aims to reconstruct the variable framework of cartilage areas so that loads can be distributed efficiently without re-injuring themselves. Cartilage dECM is intended to induce chondrocytes to generate chondrogenesis or neocartilage ECM and can be embedded in three-zone scaffolds for long-term loading. Additionally, strategies for using neural TE in the treatment of peripheral nerve injury (PNI), spinal cord injury (SCI), and stroke include the development of biomaterials that help guide remyelination and axonal regeneration, thereby preventing cavitation, improving electrical signal conductivity and increasing the survival rate of transplanted cells.
Since adipose dECM has the natural ability to drive adipose stem cell (ASC) adipogenic differentiation and adipogenesis, it is a suitable choice for adipose TE scaffolds for ASC culture growth. Biomaterials made of skeletal muscle dECM (SM-dECM) are intended to mimic the striated arrangement of native muscles while stimulating vasculogenesis and myogenesis. Liver-derived biomaterials can provide the matrix signals necessary for efficient hepatocyte culture and anatomically ordered regeneration of liver tissue. Engineering techniques in TE bone aim to create bioactive materials, which encourage the differentiation of mesenchymal stromal cells (MSCs) into osteoblasts that are crucial for new bone formation.
Demineralized bone matrix (DBM) particles have been used to repair bone defects and promote osteoblast differentiation. Rather than DBM, bone dECM can drive osteogenesis and can be easily modified to meet the needs of defects without the risks associated with foreign deoxyribonucleic acid (DNA).
When configured with different architecture and skin cells, the biomolecular signals present in the cutaneous dECM possess the ability to recreate functional characteristics of the skin. Lung TE has focused on two areas: Distal Lung Drug Carriers and Whole Lung Replacements.
Advances in other fabric types
Gastrointestinal (GI) dECM biomaterials have been developed for stimulation of neo-ECM deposition and control of chronic inflammation in radiation esophagitis and ulcerative colitis (UC) damaged gastrointestinal tract. The main TE issues for GI dECM biomaterials involve the recreation of segment-specific muscle and mucosal layers, as well as the restoration of motility function for peristalsis of the intestinal tract. In a rat model, an injectable colonic dECM hydrogel has been studied in the repair of colonic mucosa in severe UC.
There have been attempts to use corneal ECM biomaterials to mimic collagen fiber density and differential structural organization in the corneal layers, as well as to modify corneal keratocyte phenotypes while maintaining optical viscoelasticity and transparency. . Pancreatic dECM biomaterials have the ability to create a synthetic pancreatic microenvironment for islet preservation or β-cell differentiation.
Applications of dECM biomaterials currently cover a wide range of tissues, from scaffolds to patches, matching physicochemical parameters and recreating entire organs. Current limitations could be overcome by improving the decellularization surface, matching cell content and tissue-specific structures, and using composites to improve the mechanical stability of the dECM.
Biomaterials made of ECM particles are an excellent prospect for TE applications; Nevertheless, current dECM biomaterials have many limitations that need to be overcome by reducing design and variability for tissue-specific uses. According to the authors, future research should focus on tissue-specific physicochemical characteristics to address the mechanical, functional, and structural needs of the target tissue while modulating the immune response.
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Brown M., Li J., Moraes C., Tabrizian M., Li-Jessen NYK., Decellularized Extracellular Matrix: Promising and Challenging New Biomaterials for Regenerative Medicine, Biomaterials (2022), do: https://www.sciencedirect.com/science/article/pii/S0142961222004264?via%3Dihub