What is ECM?

All tissues and organs contain the extracellular matrix (ECM), a non-cellular substance that serves as a physical scaffold for the cellular components and initiates vital biochemical and biomechanical signals necessary for tissue morphogenesis, differentiation, and homeostasis (1).

The structures and functions of extracellular matrices (ECMs), which are multifaceted, well-organised, three-dimensional architectural networks, are crucial for tissue organisation and remodelling as well as for controlling cellular functions. Collagens, proteoglycans (PGs) and glycosaminoglycans (GAGs), elastin and elastic fibres, laminins, fibronectin, and other proteins and glycoproteins, including matricellular proteins, are the constituents of these ultrastructures (2).

The most prevalent protein in human tissue and the most important part of the extracellular matrix is collagen(3).

ECM in healing

Healing is needed for several incidences for example surgical incisions or a clean laceration, soft tissue loss such as ulcerations, severe burns, and major surgeries.  These tissues heal with the help of several ECM components; granulation tissue formation, which is followed by the production of extracellular matrix (ECM), largely because of fibroblasts. Collagen provides tensile strength but leaves a scar this is because elastin is not produced which is present in the native skin(4).  

Current techniques involve the capacity of scaffolds to imitate native extracellular matrix (ECM) at scale makes their microarchitecture relevant to tissue engineering. This is believed to promote cellular ingrowth, ECM deposition, and the development of neotissue (4).

Tissue polarity and asymmetric stem cell division are maintained by the ECM acting as a point of anchoring for the cells. Growth factors can bind to many ECM components, regulating their release and presentation to target cells.  Because it creates morphogen gradients, this is particularly significant in morphogenesis.  Numerous intracellular signalling pathways and cytoskeletal machinery are activated when the extracellular matrix (ECM) sends mechanical signals to the cells(3). 

ECM-Based Therapies

Several scaffolding techniques are used to heal peri-implant soft tissues for example Decellularized human dermis, Human amniotic membrane, Bilayer collagen matrix, Volume-stable collagen matrix and many more(5).

The use of three-dimensional (3D) cell culture, Scaffolds, Hydrogels, Decellularized tissues, Microfluidics, Extracellular matrix (ECM) for cancer research as these techniques are more cost effective as well as ethical(6).

Through the transplantation of bone tissue engineering scaffolds to the bone defect site and the subsequent bodily replacement of the scaffold materials with new bone tissues, the combination of scaffolds, seed cells, and cytokines aims to repair the bone defect. Scaffold, a transient and synthetic extracellular matrix, directly affects cell proliferation and differentiation and can stimulate the growth of new bone(7).

Conclusion

The extracellular matrix (ECM) is a dynamic and vital component of tissue regeneration, directing cellular activity and the healing process. It is much more than just a structural framework. Scientists are creating innovative treatments, such decellularized scaffolds and synthetic mimics, that have great potential for mending injured tissues and organs by comprehending and utilising the natural features of the extracellular matrix. We are getting closer to a time when regenerative medicine may fully utilise the body’s own healing mechanisms as long as research into the ECM continues to reveal its full potential. In addition to providing patients with injuries or degenerative diseases with hope, this opens the door for novel, transformative therapies. The ECM serves as a reminder that sometimes the finer aspects of our own biology hold the secret to healing.

References

1.           Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci [Internet]. 2010 Dec 15 [cited 2025 Mar 11];123(24):4195. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC2995612/

2.           Karamanos NK, Theocharis AD, Piperigkou Z, Manou D, Passi A, Skandalis SS, et al. A guide to the composition and functions of the extracellular matrix. FEBS J [Internet]. 2021 Dec 1 [cited 2025 Mar 11];288(24):6850–912. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/febs.15776

3.           Walker C, Mojares E, Del Río Hernández A. Role of Extracellular Matrix in Development and Cancer Progression. Int J Mol Sci [Internet]. 2018 [cited 2025 Mar 11];19(10). Available from: https://pubmed.ncbi.nlm.nih.gov/30287763/

4.           Diller RB, Tabor AJ. The Role of the Extracellular Matrix (ECM) in Wound Healing: A Review. Biomimetics [Internet]. 2022 Sep 1 [cited 2025 Mar 11];7(3):87. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9326521/

5.           Tavelli L, McGuire MK, Zucchelli G, Rasperini G, Feinberg SE, Wang HL, et al. Extracellular matrix-based scaffolding technologies for periodontal and peri-implant soft tissue regeneration. J Periodontol [Internet]. 2020 Jan 1 [cited 2025 Mar 11];91(1):17–25. Available from: https://pubmed.ncbi.nlm.nih.gov/31475361/

6.           Abuwatfa WH, Pitt WG, Husseini GA. Scaffold-based 3D cell culture models in cancer research. J Biomed Sci [Internet]. 2024 Dec 1 [cited 2025 Mar 11];31(1):7. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10789053/

7.           Su X, Wang T, Guo S. Applications of 3D printed bone tissue engineering scaffolds in the stem cell field. Regen Ther [Internet]. 2021 Mar 1 [cited 2025 Mar 11];16:63. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7868584/