Potential of Extracellular Matrix Molecules in Pharmaceutical Development

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Background

The extracellular matrix (ECM) is a complex cell-secreted network composed of a diverse array of fibrous proteins, proteoglycans, and proteolytic enzymes. Comprising approximately one-third of the human body, the ECM was initially considered to be an inactive, space-filling scaffold that provides structural support for cell growth. Thus, although abnormalities in the ECM have been observed in various human diseases and the influence of medicine on the ECM is well known, only a limited number of drugs that specifically target ECM components have been developed since the start of the new century. Accumulating data currently demonstrate that the ECM is a dynamic structure that also directly interacts with growing cells, and hence, the ECM has the capacity to modulate cell function and behaviour. Therefore, the ECM and its properties should be considered when developing ground-breaking pharmaceuticals.

One exciting application of ECM based-therapeutics is the use of decellularized ECMs. By removing the cellular components from the ECM, a decellularized ECM acts as a water-insoluble matrix and retains the physiological ECM properties that mimic the native microenvironment and support tissue regeneration. The intact biocompatibility, biodegradability, and bioinductivity of decellularized ECMs make them broadly applicable to various kinds of tissue regeneration.

It is worth noting that the structure and organization of the ECM are essential for its bioactivities. In particular, the viscosity and elasticity of the ECM are important for governing cell fate, and disruption of these properties can contribute to multiple pathologies. Since different cell types exhibit diverse mechanosensitivities, understanding and developing pharmacological interventions that adjust the ECM and/or decellularized ECM viscosity and elasticity, and thus, enhance tissue regeneration, are currently emerging in clinical medicine.

In addition, the ECM functions as a physical barrier that can diminish drug penetration, and as a result, drug efficacy, which is particularly critical for cytotoxic chemotherapeutics that target tumour growth and proliferation. Strategies that modify ECM architecture, such as those that are metalloproteinase-based, to enhance drug perfusion and improve therapeutic efficiency are urgently needed.

Matricellular proteins that do not function as structural blocks are also critical components of the ECM. In comparison with fiber-forming ECM elements, such as collagen, matricellular proteins may be more applicable in pharmaceutical development. Indeed, significant efforts have been devoted to developing matricellular protein-based pharmaceuticals, especially for cancer therapeutics and fibrotic and inflammatory diseases.

In summary, this Research Topic aims to give an overview of the most exciting progress in the field of ECM-based strategies in pharmaceutic development, including, but not limited to, the aforementioned areas. While the clinical applications of ECM-based pharmaceutics are still early in development, many promising projects are in advanced experimental stages and/or preliminary clinical trials. Given the exciting developments in the field, we believe that this Research Topic will provide further insight into the establishment of novel ECM-based strategies that can be used to pave the way for these revolutionary emerging materials that have the potential to improve human health worldwide.

Topic Editor Dr Zhong Zheng is employed by company Scarless Laboratories Inc. All other Topic Editors declare no competing interests with regards to the Research Topic subject. 

Keywords: extracellular matrix (ECM), decellularized ECM, matricellular proteins, proteoglycans, proteolytic enzymes

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