Decellularization: ECM Preservation
Decellularization of tissue represents one of the most critical starting points in the preparation of ECM-based scaffolds for application in regenerative medicine. The ultimate idea of decellularization is to take out all cellular material that might potentially trigger an immune response while still preserving the ECM’s structural and biochemical properties. The decellularization of various tissues has been shown to be effective using chemical, enzymatic, and physical methods. Each of these methods has some relative benefits and challenges, depending on the tissue type.
Most of the chemical ways in which decellularization is carried out rely on detergents such as SDS or Triton X-100, known to easily extract cellular components but with the potential to damage the delicate structure of the ECM. Enzymatic methodologies specifically directed at cellular components through the use of trypsin or nucleases may offer a more controlled process of decellularization. These are physical methodologies, including freeze-thaw cycles and high hydrostatic pressure, that provide mechanical methods of cell removal without damaging the ECM’s architecture.
Nonetheless, the majority of developing decellularization techniques are focused on relatively preserving components of the ECM, such as collagen or glycosaminoglycan, which are responsible for maintaining the scaffold’s function. For example, scCO2 can be mentioned as one of the methods that have shown very promising results in the decellularization of dense tissues, such as cartilage or tendons, recently. Such a technique preserves the structure of the ECM with its biomechanical properties and effectively removes the cellular material.
Applications of DCM in Regenerative Medicine
Of course, by now, the versatility of ECM in regenerative medicine has already given rise to lots of diversified applications across different tissues and organs in ongoing research. In particular, one of the most active uses of DCM-based scaffolds is in the development of bioinduced tissues for transplantation. Those examples range from decellularized heart valves, blood vessels, and skin grafts to more novel clinical applications for the provision of biocompatible and functional alternatives to synthetic materials.
The skin is the largest organ of the human body and the natural barrier to a hostile environment. In such cases, the wound or burn heals through intrinsic healing, which is insufficient and might end up forming a chronic wound or large scar. ECM-based scaffolds prepared using either the decellularized dermis or amniotic membrane have shown great promise in enhancing wound healing and tissue regeneration. These scaffolds are such that they give the cells appropriate help in attachment and spreading; therefore, they aid the healing process and work very well in lowering scar formation.
The creation of more vascularized tissue with ECM scaffolds aims to represent one of the research focuses in the skin tissue engineering domain in recent years. This will ably ensure the survival and integration of the implanted tissues after the process, as the blood supply will be readily available to provide for oxygen and nutrients. It has resulted in better skin regeneration through the incorporation of growth factors, stem cells, and revascularization techniques for an improved antigenic potential of the ECM scaffolds.
Cartilage and regeneration Both cartilage and bone are considered two of the most challenging tissues to be repaired using tissue engineering methodologies, mainly because of the structure and mechanical demands of such tissues. The ECM in both cartilage and bone can provide structurally supportive functions, but at the same time, it contains encoded biochemical signals that are very critical for the regulation of cell activity and tissue homeostasis. Decellularized ECM scaffolds of cartilage and bone have been used to develop new tissue engineering strategies for the regeneration of functional cartilaginous and osseous tissues.
Research has been conducted on synthetic and hybrid scaffolds that combine natural components of ECM with the needed synthetic polymers in hopes of achieving desired mechanical properties combined with biological functionality for the engineering of cartilage tissue. The former scaffolds will induce the proliferation and differentiation of chondrocytes, besides investing in the re-cartilation with appropriate biomechanical characteristics by themselves. To that end, decellularized bone ECM scaffolds have already been applied to provide enabling conditions for the growth and maturation of estrogenic cells for inducing ontogenesis.
The cardiovascular system is composed of blood vessels, heart valves, and myocardium from a mechanical functionality point of view. A good amount of research has been done regarding the repair or replacement of cardiovascular tissues and ECM-based tissue-engineered scaffolds. For example, the use of decellularized vascular grafts provides a more biocompatible approach to synthetic grafts, which is an advantage since these grafts result in endothelialization at their launch and reduce the risk of thrombosis.
