Citation: Fernández-Guarino, M.;
Hernández-Bule, M.L.; Bacci, S.
Cellular and Molecular Processes in
Wound Healing. Biomedicines 2023,
11, 2526. https://doi.org/10.3390/
biomedicines11092526
Academic Editors: Gerrit Grieb
and Franco Cervellati
Received: 26 June 2023
Revised: 10 September 2023
Accepted: 11 September 2023
Published: 13 September 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
biomedicines
Review
Cellular and Molecular Processes in Wound Healing
Montserrat Fernández-Guarino
1
, Maria Luisa Hernández-Bule
2
and Stefano Bacci
3,
*
1
Dermatology Service, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (Irycis),
28034 Madrid, Spain; drafernandezguarino@gmail.com
2
Bioelectromagnetic Lab, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (Irycis),
28034 Madrid, Spain; mluisa.hernandez@hrc.es
3
Research Unit of Histology and Embriology, Department of Biology, University of Florence, Viale Pieraccini 6,
50134 Firenze, Italy
* Correspondence: stefano.bacci@unifi.it
Abstract: This review summarizes the recent knowledge of the cellular and molecular processes
that occur during wound healing. However, these biological mechanisms have yet to be defined
in detail; this is demonstrated by the fact that alterations of events to pathological states, such as
keloids, consisting of the excessive formation of scars, have consequences yet to be defined in detail.
Attention is also dedicated to new therapies proposed for these kinds of pathologies. Awareness of
these scientific problems is important for experts of various disciplines who are confronted with these
kinds of presentations daily.
Keywords: acute wounds; cellular infiltrate; chronic wounds; keloids; scars
1. Introduction
The development of knowledge about wound healing (WH) throughout history has
been remarkable. Historically, wounds were often related to infection, and patients conse-
quently died from septicemia rather than from the wound itself. With the advent of light
microscopy, a greater awareness of the fine cellular mechanisms of wounds has evolved,
and this has aided our understanding of the treatment and care needed. Nevertheless,
compromised WH is a major concern in public health. This is demonstrated by the fact that
millions of people suffer from chronic wounds (CWs) [1,2].
2. Issues Related to the Study and Management of Wound Healing
Impaired WH appears to be a major concern in the public health sector, as expensive
and complex treatments are necessary for its management. Millions of patients need care
for chronic wounds and this costs thousands of millions in USD. This burden is increas-
ing, mainly due to the growing incidence of aging, diabetes, and other risk factors in
the population. A similar scenario is observed in Europe, where it is estimated that over
1.5 million people could be affected by CWs. As a result, WH is of great interest, and
this is demonstrated by the number of fellowship programs offered for various medical
professionals in this field, including vascular surgeons, nurses, dermatologists, and general
practitioners. There is a demand for new technologies in WH to be introduced. Further-
more, additional problems exist because a comprehensive understanding of the biological
mechanisms related to wound healing has not yet assumed popular relevance; rather, the
focus is more directed toward niche problems, where, contrary to some disciplines, few
scholars confront each other regarding the problems considered [1–3].
Guidelines undoubtedly represent an aid for wound care during clinical practice [4,5],
in particular considering the fact that the biofilm, which maintains the CW in the inflam-
matory phase, is responsible for 80% of infections and must be removed [5]. Among the
new techniques, it is particularly worth mentioning those concerning the effects of four
Biomedicines 2023, 11, 2526. https://doi.org/10.3390/biomedicines11092526 https://www.mdpi.com/journal/biomedicines