Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

Abstract

Whereas the physiologic wound healing (WH) successfully proceeds through the clearly defined sequence of the individual phases of wound healing, chronic non-healing wounds/ulcers fail to complete the individual stages and the entire healing process. There are many risk factors both modifiable (such as stress, smoking, inappropriate alcohol consumption, malnutrition, obesity, diabetes, cardio-vascular disease, etc.) and non-modifiable (such as genetic diseases and ageing) strongly contributing to the impaired WH. Current statistics demonstrate that both categories are increasingly presented in the populations, which causes dramatic socio-economic burden to the healthcare sector and society at large. Consequently, innovative concepts by predictive, preventive and personalised medicine are crucial to be implemented in the area. Individual risk factors, causality, functional interrelationships, molecular signature, predictive diagnosis, and primary and secondary prevention are thoroughly analysed followed by the expert recommendations in this paper.

Use of platelet‐rich plasma to facilitate wound healing

“…In these cases, keratinocytes do not proliferate and migrate properly, which destabilise wound healing by inhibiting epidermalisation . There are a number of studies showing that comorbidities (endocrine diseases, diseases of the cardiovascular system), repeatedly performed operations, and damaging lifestyle habits impair wound healing, and could lead to complications in the early operative period, such as suppuration of the wound, divergence of sutures, and development of infection . Development of wound infection reduces fibroblast migration and proliferation, which leads to a downregulation of collagen synthesis and a delayed healing process.…”

A pilot multi‐centre prospective randomised controlled trial of RECELL for the treatment of venous leg ulcers

“…The complexity of the wound and healing capacity is known to be impacted by age, smoking, comorbidities, as well as wound size, and chronicity of the wound. [40][41][42] Post hoc analyses were conducted for parameters with statistical significance between treatment groups (age, smoking), as well as those not reaching statistical significance individually, but were of clinical importance and may have a combined effect on the results of the trial. Results of logistic regression analysis on incidence of ulcer closure, Cox regression analysis for time to ulcer closure, and ANCOVAs for change in pain, wound size, CCVLUQ score, and satisfaction were conducted at Week 12 between treatment groups and no further statistical differences were found; however, it should be noted that the sample sizes in this study were limited.…”

Inappropriate modeling of chronic and complex disorders: How to reconsider the approach in the context of predictive, preventive and personalized medicine, and translational medicine

“…Both, modifiable risk factors (such as stress, smoking, inappropriate alcohol consumption, malnutrition, obesity, diabetes, and cardiovascular disease) and nonmodifiable risk factors (such as genetic diseases and aging), have been identified in the process of impaired wound healing, which calls for implementation of PPPM approach in this area [100]. Individual risk factors, causality, functional interrelationships, molecular signature, predictive diagnosis, and primary and secondary prevention are all crucial in approach to impaired wound healing [34].…”

“…On the other hand, animal models of wound healing are extremely simplified; almost none of comorbidities and risk factors of impaired wound healing has been modeled on them. Among the important risk factors that were not presented in the majority of models are aging, smoking, malnutrition, obesity, diabetes, and cardiovascular disorders [100,101].…”