The mechanics of wound healing.

This paper discusses the factors which affect the healing of wounds at the tissue and organ levels. It covers some of the problems which complicate the sequence of healing and considers the mechanisms involved in regeneration and repair of tissues. The factors associated with the stimulus and sequence of healing and their interactions are also reviewed.     

Stages of wound healing and their clinical relevance.

Wound healing describes the host mechanisms involved in the process of restoring the continuity of tissues after injury. Wound healing progresses through a continuum of overlapping stages characterized by macroscopic, microscopic, and biochemical events. An understanding of the relation between these events can enhance clinicians' skills in wound management.     

Principles of wound healing

Wound healing can be divided into immediate (zero to 1 hour), early (1 to 24 hours), intermediate (1 to 7 days), and late (greater than 7 days) stages. Many physical and physiologic events occur simultaneously and sequentially during these stages to produce the final wound scar. The processes of skin retraction, scab formation, would debridement, wound contraction, epithelial migration and proliferation, fibroplasia, and collagen maturation all must occur for healing to be successful. Many factors affect the size and shape of the resulting scar, including anatomic location and skin tension forces, systemic condition of the patient, blood supply to the wound, nutritional factors, environmental temperature, the presence of systemic drugs, wound infection, motion, wound oxygen gradient, wound moisture, and bandaging. Ideally, each of the factors would occur at a level compatible with optimal healing, but, in many clinical cases, one or more factors compromise normal, rapid healing. When we intervene with therapy, we probably adversely affect another factor in healing, while trying to correct the factor that is out of balance. In these decisions, the effects of our treatment on wound healing should be considered. The trade-off should be weighed and the treatment pursued only as long as necessary to allow healing to progress; then it should be discontinued or changed. With these considerations, it is hoped that we can attain healing at the most rapid physiologic rate.     

Cutaneous wound healing in the cat: a macroscopic description and comparison with cutaneous wound healing in the dog

OBJECTIVE: To describe the macroscopic features of first and second intention cutaneous wound healing in the cat and compare with the dog. STUDY DESIGN: Experimental study. ANIMALS: Domestic shorthaired cats (6) and beagle dogs (6). METHODS: Square, open cutaneous wounds created on the dorsal aspect of the thorax were evaluated for 21 days for temporal and spatial development of granulation tissue, wound contraction, epithelialization, and total healing. To evaluate first intention healing, breaking strength of sutured linear cutaneous wounds was measured at 7 days post-wounding. Laser-Doppler perfusion imaging was used to measure cutaneous perfusion. RESULTS: First intention healing: sutured wounds in cats were only half as strong as those in dogs at day 7 (0.406 versus 0.818 kg breaking strength). Second intention healing: cats produced significantly less granulation tissue than dogs, with a peripheral, rather than central distribution. Wound epithelialization and total wound healing (total reduction in open wound area from contraction and epithelialization) were greater for dogs than for cats over 21 days. Wound contraction on day 7 was greater for dogs, but not on day 14 or 21. Cutaneous perfusion was initially greater for dogs than for cats, but no differences were detected after day 7. CONCLUSIONS: Significant, previously unreported differences in cutaneous wound healing exist between cats and dogs. In general, cutaneous wounds in cats are slower to heal. Cats and dogs also appear to use different mechanisms of second intention healing. In cats wounds close mainly by contraction of the wound edges, whereas in dogs wounds close more from central pull, and epithelialization. CLINICAL RELEVANCE: Surgeons should view the cat as a unique species, which presents its own special challenges in wound healing, and should take this into account when planning treatment of feline wounds, either by primary closure, or by second intention healing.     

The effect of low level laser therapy (LLLT) on wound healing in horses.

Laser therapy is used in many countries, including South Africa, for the treatment of skin wounds. Low level galium aluminium arsenide (GaAlAs) laser was administered to full thickness skin wounds (3 x 3 cm) induced surgically on the dorsal aspect of the metacarpophalangeal joints of 6 crossbred horses in a randomised, blind, controlled study. Treated wounds that received a daily laser dosage of 2 J/cm2 were compared with nontreated control wounds on the opposite leg. There were no wound complications. Both groups of wounds were cleaned daily using tap water. Wound contraction and epithelialisation were evaluated using photoplanimetry. There were no significant differences in wound contraction or epithelialisation between the laser treated and the control wounds. It was therefore concluded that laser therapy had no clinically significant effect on second intention wound healing in this study.     

Differences in cutaneous wound healing between dogs and cats.

Regardless of the species involved, wound healing follows a predictable course of overlapping phases. In spite of these commonalities, significant species differences in cutaneous wound healing have been uncovered in the Equidae and, more recently, between the dog and cat. It has also recently been shown that the subcutaneous tissues play an important supporting role in cutaneous wound healing, which may help to ex-plain healing differences between cats and dogs. These discoveries may improve veterinarians' understanding of problem wound healing in the cat and, hopefully, lead to better strategies for wound management in this sometimes troublesome species.     

Ferrets. Examination and preventive medicine.

As ferrets are anatomically and physiologically similar to dogs and cats, the basic elements of ferret examination, disease processes, and preventive health are familiar to small-animal practitioners. Like other domestic carnivores, ferrets are tolerant of handling and medical procedures, especially compared with rabbits, rodents, and most nondomestic mammals. These characteristics make ferrets amenable to many of the highly specialized diagnostic and therapeutic techniques that are now available in small-animal practice. Veterinarians who wish to add ferrets to their practices should be familiar with the ferret literature, but they should not forget to draw from the wealth of knowledge in canine and feline medicine when managing unusual or difficult ferret cases.     

Topical therapeutic agents that modulate corneal wound healing.

In summary, corneal wound healing is a complex phenomenon that involves interplay between the cellular elements of the cornea, numerous soluble factors, and the constituents of the ECM. Unfortunately, many studies that demonstrate marked alteration on cell behavior in vitro and even in in vivo experiments are often not helpful in the diseased patient, as shown by the results of careful clinical trials. Future work that addresses the complex milieu of the corneal wound healing environment by addressing the interaction of many of these factors will be more likely to be successful than seeking a single agent that will enhance wound healing in all situations.Modulation of wound healing processes by the application of topical therapeutic agents is, however, an expanding field of study sure to produce clinically significant improvements in the management of veterinary patients with corneal defects. The judicious use of topical cytoactive compounds has a place in the clinician's armamentarium integrated into a therapeutic plan that decreases the mechanical stresses imposed on the wound bed as well as removal of any underlying inciting cause.     

The effects of topical oxygen therapy on equine distal limb dermal wound healing

Topical oxygen therapy (TOT) has been used in human medicine to promote healing in chronic wounds. To test the efficacy and safety of TOT in horses, an experimental wound model was created by making 1 standardized dermal wound on each limb of 4 healthy horses (n = 16). Each wound was fitted with an oxygen delivery cannula and covered with a bandage. One limb of each front and hind pair was randomly assigned to the treatment group (fitted with an oxygen concentrator device), with the contralateral limb assigned to the control group (no device). Wound area, epithelial area, and contraction were measured every 3 to 4 d. Biopsy samples and culture swabs were taken on days 16 and 32 to evaluate angiogenesis, fibroplasia, epithelial hyperplasia, inflammation and bacterial growth. Mean healing time in treated wounds (45 d, range: 38 to 52 d) was not significantly different from that in the paired control wounds (50 d, range: 38 to 62 d). Topical oxygen therapy had little effect on dermal wound healing in this experimental wound model in healthy horses.     

Ferrets. Clinical pathology and sample collection.

Diagnostic sampling and interpretation in the ferret are similar to other small mammals in many ways. There are several aspects of clinical pathology and diagnostic procedures, however, that are unique to the ferret. This article is designed to assist the clinician in obtaining and interpreting diagnostic samples for the ferret. Methods for blood and urine collection, bone marrow and organ aspirations, and organ biopsy techniques are discussed.     

Advances in wound healing physiology: the comparative perspective

Abstract Understanding of the processes involved in wound healing in vertebrates is increasing rapidly owing to the application of advances in cell and molecular biology, and in technology. The cellular mechanisms which result in some vertebrates having the ability to regenerate the dermis after injury, whereas in others it is replaced by scar tissue, are currently being explored with a view to restoring this regenerative ability by modulating the intercellular systems which control wound healing. This introductory review (a) compares and contrasts the response to injury of homoiofhermic and poikilothermic animals and of foetal and post-natal mammals; (b) describes the mechanisms involved in cutaneous wound healing; (c) illustrates how the rate and quality of healing can be assessed non-invasively and objectively, and (d) describes how cutaneous healing can be improved by the application of electrophysical modalities employing ultrasound and light. Zusammenfassung Unser Verständnis von Wundheilungsprozessen bei Wirbeltieren wächst wegen der Fortschritte in Zell- und Molekularbiologie und Technologie rapide. Die zellulären Mechanismen, die es einigen Wirbeltieren ermöglichen, die Haut nach einer Verletzung zu regenerieren, während sie bei anderen durch Narbengewebe ersetzt wird, werden gegenwärtig erforscht, um diese Regenerationsfähigkeit durch Veränderung der interzellulären Systeme, die die Wundheilung kontrollieren, wiederherzustellen. Diese einführende Übersicht (a) vergleicht die Reaktion auf Verletzung in homiothermischen und poikilothermischen Tieren und in Säugetierfeten und Säugetieren nach der Geburt; (b) beschreibt die Mechanismen der kutanen Wundheilung; (c) illustriert, wie die Heilungsrate und -fähigkeit nichtinvasiv und objektiv bewertet werden kann, und (d) beschreibt, wie Wundheilung durch die Anwendung von elektrophysikalischen Heilmitteln wie Ultraschall und Licht verbessert werden kann. [Dyson, M. Advances in wound healing physiology: the comparative perspective (Fortschritte in der Wundheilungsphysiologie: die vergleichende Perspektive). Veterinary Dermatology 1997; 8 : 227–233] Resumé La compréhension des processus impliqués dans la cicatrisation des plaies chez les vertébrés croït rapidement suite à l'application des progrès en biologie cellulaire et moléculaire et en technologie. Les mécanismes cellulaires qui résultent chez certains vertébrés dans la capacité du derme à se régénérer après une blessure alors que chez d'autres, il est remplacé par du tissus cicatriciel, sont actuellement explorés avec pour but de restaurer cette capacité régénératrice en modulant les systèmes intercellulaires qui contrôlent la cicatrisation des plaies. Cette revue d'introduction (a) compare et contraste la réponse des animaux homoiothermiques et poikilothermiques et des mammifères foetaux et postnataux au traumatisme; (b) décrit les mécanismes impliqués dans la cicatrisation des plaies; (c) illustre comment le taux et la qualité de cicatrisation peuvent être évalués de manière non invasive et objective; et (d) décrit comment la cicatrisation cutanée peut être améliorée par l'application de modalités électrophysiques utilisant ultra sons et lumière. [Dyson, M. Advances in wound healing physiology: the comparative perspective (Progres de la physiologie de la cicatrisation des plaies: les perspectives comparatives). Veterinary Dermatology 1997; 8 : 227–233] Resumen El conocimiento de los procesos implicados en la curación de heridas en los vertebrados aumenta rápidamente debido a la aplicación de avances en biologia celular y molecular, y a la tecnologia. Actualmente se estan estudiando los mecanismos celulares que hacen que algunos vertebrados tengan la capacidad de regenerar la dermis después de una herida, mientras que en otros se sustituye por tejido de cicatrización, con el objetivo de restaurar la capacidad regenerativa modulando los sistemas intercelulares que controlan la curación de heridas. Esta revision introductoria a) compara y contrasta la respuesta a las heridas en animales homoiotermos y poiquilotermos y en mamiferos fetales y post-natales; b) describe los mecanismos implicados en la curación de heridas cutáneas; c) ilustra cómo el ritmo y la calidad de curación puede ser monitorizado de forma no-invasiva y objetiva y d) describe como la curación cutánea mejora mediante la aplicación de modalidades electrofisicas utilizando ultrasonidos y luz. [Dyson, M. Advances in wound healing physiology: the comparative perspective (Avances en fisiologia de la curación de heridas: perspectiva). Veterinary Dermatology 1997; 8 : 227–233]     

The mast cell in wound healing

This review describes the role of the mast cell in the pathobiology of skin healing. After illustrating its main morphofunctional characteristics, with special reference to the dog and cat, we consider the involvement of the mast cell in the various phases of skin repair. With the aid of a wide array of newly formed or preformed mediators released by degranulation, the activated mast cell controls the key events of the healing phases: triggering and modulation of the inflammatory stage, proliferation of connective cellular elements and final remodelling of the newly formed connective tissue matrix. The importance of the mast cell in regulating healing processes is also demonstrated by the fact that a surplus or deficit of degranulated biological mediators causes impaired repair, with the formation of exuberant granulation tissue (e.g. keloids and hypertrophic scars), delayed closure (dehiscence) and chronicity of the inflammatory stage.