The dynamic process of wound healing has various phases, knowledge of which is essential for identification of the pathology involved in a chronic intractable wound. Various instruments for the assessment of wound healing have been described, primarily for clinical assessment of the wound. However, very few instruments are currently available for histological grading of the wound. The aim of this article is to review all available literature from 1993 to 2014 on the objective histological scoring of the state of wound healing. This review article emphasizes the importance of histological grading of wounds based on the different parameters from each phase of wound healing, and the need for an ideal grading system in order to help assessment of wound status. The parameter chosen in an experimental model should be defined by the scientific question, the underlying hypothesis and the pathogenesis of the disease.
The dynamics of wound healing are complex. A thorough understanding of the normal healing process is a prerequisite for unveiling the pathology. Wound healing begins with homeostasis at the site of injury, progresses to an inflammatory phase followed by proliferation of the epithelial and matrix components, and ends with the formation of scar tissue marked by laying down of a highly organized collagen matrix.[
Factors influencing the wound healing
Local factors | Systemic factors |
---|---|
Oxygenation | Age, gender |
Foreign body | Disease: diabetes, keloids, fibrosis, jaundice, uremia |
Blood supply | Medications: NSAIDs, glucocorticoids, chemotherapy |
Stress, nutrition, alcoholism | |
Immunocompromised status, AIDS, cancer, radiation |
NSAIDs: Nonsteroidal anti-inflammatory medications, AIDS: Acquired immune deficiency syndrome
Impaired wound healing is not an uncommon occurrence in clinical practice. Both local and systemic factors are responsible for impaired healing and weak scar tissue formation.[
Various interventions are available for amelioration of impaired healing. Hence, it is important to evaluate wound healing in order to compare the efficacy of different interventions. Wound healing is evaluated by both clinical features and biochemical and histological parameters. Nuclear medicine can assist in assessing the vascularity of healing tissue, and hence plays a role in recording inflammation. However, study of the histological features appears to be more reliable as the findings can be recorded photographically for evaluation by different experts.
A literature search was performed on histological scoring of wound from 1993 to 2014. A total of 30 available relevant literatures on wound healing and histological scoring based on various parameters from different stages of wound healing were selected for review.
The sequence of events in normal wound healing have been widely studied and described in literature.[
The wound healing process consists of four phases: hemostasis, inflammation, proliferation and remodeling.[
The initial step assists in protection of the vascular system to maintain functionality of the organ. The clot formed as a result of coagulation provides a matrix for the cells involved in subsequent steps of hemostasis and inflammation.[
The goal of the inflammatory phase is to fight potential bacterial contamination of the wound and to activate cytokine secretion.[
The proliferation phase overlaps with the preceding inflammatory phase. It represents a proliferation of both epithelial and dermal elements which results in reepithelialization of the wound and laying down of the primary extracellular matrix.[
This phase marks the final step of tissue remodeling and differentiation leading to recovery of the skin and its aesthetic restoration.[
Impaired wound healing occurs secondary to disordered collagen formation[
Because healing is a dynamic process, it is difficult to evaluate and requires consistent measurements.[
Various tools for assessing wound healing clinically have been described, including the Pressure Ulcer Score of Healing (PUSH), the Sussman Wound Healing Tool (SWHT), the Wound Healing Scale (WHS), the Leg Ulcer Measurement Tool (LUMT) and the granulometer.[
The assessment of the histological state of the healing wound is important in clinical practice for postoperative patient management.[
Comparison of histologic patterns with the known physiologic variation in tissue morphology assists in qualitative derivation of the diagnosis. The degree of changes observed when scored on an ordinal scale, namely, low, medium or high grade, provides a semi-quantitative score. On the other hand, the exact quantitative measurement in terms of the absolute number of cells and areas of tissue gives a quantitative score.[
Various studies have been conducted, and wound healing models have been proposed to understand the normal healing process and to standardize the semi-quantitative and quantitative evaluation of selected parameters of wound healing. In a study assessing wound healing in the maxillofacial region, Sulthana
Parameters assessed to calculate healing score
Number | Histological Parameter |
---|---|
1 | Amount of granulation tissue (profound-1, moderate-2, scanty-3, absent-4) |
2 | Inflammatory infiltrate (plenty-1, moderate-2, a few-3) |
3 | Collagen fiber orientation (vertical-1, mixed-2, horizontal-3) |
4 | Pattern of collagen (reticular-1, mixed-2, fascicle-3) |
5 | Amount of early collagen (profound-1, moderate-2, minimal-3, absent-4) |
6 | Amount of mature collagen (profound-1, moderate-2, minimal-3) |
Number 1-4: H and E, Number 5-6: Masson’s trichrome stain, old collagen fibers take deep blue color and the new collagen fibers stain light blue
While studying the overall process of wound healing, Braiman-Wiksman
Histological skin cell parameters for the assessment of wound healing
Healing parameter | Assessment parameter |
---|---|
Epidermal closure | Basal layer of the epidermis to assess the newly formed epidermis |
Epidermal differentiation | Spinous epidermal differentiation (early) |
Epidermal migration | Migrating cells |
Granulation tissue formation and Epidermal hyperplasia | Proliferating cells |
Granulation tissue and matrix formation | Collagen fiber deposition |
Inflammation dermal closure | White blood cells abscesses matrix remodeling |
Late stage of matrix remodeling | Elastin fiber deposition |
In their experimental model of open-skin wound healing in corticosteroid-treated and diabetic rats, Gal
Parameters of histologic assessment of wound
Semi-quantitative method | Quantitative method |
---|---|
Wound reepithelialization: migration of keratinocytes, bridging of cells, keratinization | Polymorphonuclear leucocytes/tissue macrophages ratio |
Inflammatory cells: absence/presence (mild/moderate/marked) | Percentage of reepithelialization |
Fibroblasts: absence/presence (mild/moderate/marked) | Area of the granulation tissue |
New vessels: absence/presence (mild/moderate/marked) | - |
Collagen: absence/presence (mild/moderate/marked) | - |
Lemo
Parameters measured in the mathematical model
Length of the reepithelialization zone (L) |
Distance between the borders of the wound (S) |
Depth of the wound (D) |
Thickness of the connective tissue (T) |
Thickness of the natural dermis on both sides of the wound (N) |
Tascilar
Ancillary techniques such as special stains and immunohistochemistry in addition to light microscopic examination can help in the accurate assessment of the components of a healing wound. For instance, Masson’s trichrome staining is used to demonstrate the presence of collagen in the healing wound.[
Histopathology has always been the gold standard in diagnosing certain infectious, degenerative or neoplastic diseases in humans and animals.[
There are numerous scoring systems provided by various pioneers in the field. However, the need for uniformity persists. Although the selection of parameters in most scoring systems is generally based on a basic knowledge of the wound healing, the parameters chosen in an experimental model should be defined by the scientific question, the underlying hypothesis and the pathogenesis of the disease.
Nil.
There are no conflicts of interest.