Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?

Abstract

The clinical field of wound healing is challenged by numerous hurdles. Not only are wound-healing disorders complex and multifactorial, but the corresponding patient population is diverse, often elderly and burdened by multiple comorbidities such as diabetes and cardiovascular disease. The care of such patients requires a dedicated, multidisciplinary team of physicians, surgeons, nurses and scientists. In spite of the critical clinical need, it has been over 15 years since a treatment received approval for efficacy by the FDA in the United States. Among the reasons contributing to this lack of effective new treatment modalities is poor understanding of mechanisms that inhibit healing in patients. Additionally, preclinical models do not fully reflect the disease complexity of the human condition, which brings us to a paradox: if we are to use a "mechanistic" approach that favours animal models, we can dissect specific mechanisms using advanced genetic, molecular and cellular technologies, with the caveat that it may not be directly applicable to patients. Traditionally, scientific review panels, for either grant funding or manuscript publication purposes, favour such "mechanistic" approaches whereby human tissue analyses, deemed "descriptive" science, are characterized as a "fishing expedition" and are considered "fatally flawed." However, more emerging evidence supports the notion that the use of human samples provides significant new knowledge regarding the molecular and cellular mechanisms that control wound healing and contribute to inhibition of the process in patients. Here, we discuss the advances, benefits and challenges of translational research in wound healing focusing on human subject research.

Keywords: chronic ulcers; human specimens; pre-clinical models; wound healing.

FIGURE 1

Samples from chronic wounds provide a unique resource of biomaterial for mechanistic studies in wound-healing research. Chronic wound tissue can be utilized for histopathology, microbiology assessment, generation of primary cells as well as RNA, protein and lipid isolation for downstream “omics” analyses. Chronic wound fluid and swabs can also be utilized for lipid and protein evaluation as well as microbial DNA isolation followed by microbiome analyses

FIGURE 2

“Omics” approaches utilizing chronic wound samples can lead to discovery of new diagnostic and therapeutic targets. Studies focusing on human chronic wound samples and patient-derived primary cells with utilization of “omics” tools provide excellent resource for discovery and development of diagnostic tools, more personalized approach to treatments and identification of new therapeutic targets