Skin: histology and physiology of wound healing

It is important to understand the histology and physiology of skin for the prediction and optimization of wound healing. Optimal postoperative wound healing to minimize scarring entails minimizing local, systemic, and environmental factors that lead to poor wound healing. Keeping the wound clean and moist, minimizing trauma, and infection are the local wound tenets. Systemic tenets include minimizing medications that inhibit processes of wound healing, maintaining adequate nutrition, pain palliation, UV protection, and smoking cessation. This article presents the dynamic process of wound healing and the basic tenets to minimize scarring.     

Skin: histology and physiology of wound healing

It is important to understand the histology and physiology of skin for the prediction and optimization of wound healing. Optimal postoperative wound healing to minimize scarring entails minimizing local, systemic, and environmental factors that lead to poor wound healing. Keeping the wound clean and moist, minimizing trauma, and infection are the local wound tenets. Systemic tenets include minimizing medications that inhibit processes of wound healing, maintaining adequate nutrition, pain palliation, UV protection, and smoking cessation. This article presents the dynamic process of wound healing and the basic tenets to minimize scarring.     

Laser biostimulation of healing wounds: specific effects and mechanisms of action

The purpose of this article was to synthesize the scientific knowledge relevant to laser biostimulation of healing wounds. The literature reviewed suggests that biostimulation with lasers: 1) accelerates the inflammatory phase of wound healing by altering the levels of various prostaglandins, 2) increases ATP synthesis by enhancing electron transfer in the inner membrane of mitochondria, 3) quickens protein (collagen) synthesis by quickening DNA and RNA synthesis, 4) augments fibroplasia by a mechanism that is still being explored, and 5) enhances the ability of immune cells to combat invading pathogens. Although these findings were made in vitro and in vivo in various animal models, their clinical implications are quite clear. Laser biostimulation is potentially a useful tool in the treatment of wounds, particularly those cutaneous and subcutaneous wounds that are either complicated by infection or inherently require a prolonged period of time to heal. The precise dosage and frequency of treatment required to promote healing even in animal models remain elusive, as is experimental determination of the depth of penetration of lasers.J Ortho Sports Phys Ther 1988;9(10):333-338.     

Science of measurements in wound healing

Wounds that are slow to heal are poorly understood. Clinicians and researchers have attempted to predict treatment outcomes from simple physical measurements without, as yet, understanding the pathogenesis or the role of complications on chronic wounds. Laboratory studies on tissues from biopsies and wound fluids are essential. These must be associated with carefully conducted physiological measurements before, the significance of measurements in wound healing is established.     

A review of microvascular measurements in wound healing

The microcirculatory evaluation in patients affected by arteriopathic or venous ulcers is usually carried out using laser Doppler flowmetry, transcutaneous oxygen (transcutaneous pressure of oxygen, TcPO(2)), and carbon dioxide (transcutaneous pressure of carbon dioxide, TcPCO(2)) measurements and capillaroscopy. These techniques provide significant pathophysiologic and prognostic information. TcPO(2) and TcPCO(2) diagnose and classify the extent of arterial disease in the leg ulcers caused by arterial disease; the prognostic value is recognized, though doubts about its prognostic potential exist in the case of leg ulcer. Laser Doppler flowmetry is able to identify the first functional impairment in the early stages of the arterial disease and in the complicated venous insufficiency. Capillaroscopy gives us morphological and quantitative parameters of the capillary bed that is damaged in arteriopathic and venous ulcers; nevertheless, it does not provide us with definite prognostic indexes. Combining the 3 methods may contribute to yield objective measures in the clinical management of lower extremity ulcers.     

Laser wound healing compared with other surgical modalities

In this study the measured rate of healing of identical excisional wounds produced by the carbon dioxide laser and three other surgical modalities, viz.: conventional scalpel blade, electrosurgical (Bovie) unit, and plasma torch are compared.Differences in the gross and microscopic findings are discussed and partially explained.These studies would indicate that portable and easily controllable lasers have the potentiality of becoming a new type of practical surgical-knife and haemostatic instrument.     

Laser and wound healing (author's transl)

Orientating experiments upon rats did not give any information about a specific effect of laser beams on wound healing. The same results were achieved by infra red photoradiation. Further research with histological and histochemical tests will be necessary.     

Laser photostimulation accelerates wound healing in diabetic rats

In this study, we examined the hypothesis that laser photostimulation can facilitate healing of impaired wounds in experimental diabetes using a rat model. Diabetes was induced in male rats by streptozotocin injection and two 6 mm diameter circular wounds were created on either side of the spine. The left wound of each animal was treated with a 632.8 nm He:Ne laser at a dose of 1.0 J/cm2 for five days a week until the wounds closed (three weeks). Measurements of the biomechanical properties of the laser-treated wounds indicated there was a marginal increase in maximum load (16%), stress (16%), strain (27%), energy absorption (47%) and toughness (84%) compared to control wounds of diabetic rats. Biochemical assays revealed that the amount of total collagen was significantly increased in laser treated wounds (274 +/- 8.7 microg) over the control wounds (230 +/- 8.4 microg). Sequential extractions of collagen from healing wounds showed that laser treated wounds had significantly greater concentrations of neutral salt soluble (15%) and insoluble collagen (16%) than control wounds, suggesting accelerated collagen production in laser treated wounds. There was an appreciable decrease in pepsin soluble collagen (19%) in laser treated wounds over control wounds, indicating higher resistance to proteolytic digestion. In conclusion, the biomechanical and biochemical results collectively suggest that laser photostimulation promotes the tissue repair process by accelerating collagen production and promoting overall connective tissue stability in healing wounds of diabetic rats.     

Trauma and wound healing: role of the route of nutritional support

Following severe trauma and surgical injury, nutritional support via the enteral route has been shown to lead to increased survival and decreased complications when compared to the parenteral route. We hypothesized that the route of nutrient delivery may affect cutaneous wound healing following severe traumatic insult. Forty-six Sprague Dawley rats underwent bilateral closed femoral fractures, central venous catheterization, gastrostomy placement and dorsal skin incision with placement of polyvinyl alcohol sponges into subcutaneous pockets. Identical nutritional infusates of 25% dextrose, 4.25% amino acids, and vitamins were given, half the animals receiving the infusion via the gastrostomy (ENT) and the other half via the venous catheter (TPN). Animals were sacrificed on post-operative days 5, 7, or 10. Wound breaking strength (WBS, g) and sponge granuloma hydroxyproline content (OHP- a measure of wound collagen deposition, microg/ 100mg sponge) were measured. There were no significant nutritional differences between the two feeding groups. On days 5 and 7, WBS was significantly higher in the ENT group (58.0 +/- 3.1 g vs 48.9 +/- 2.6 g, p < 0.05, and 123 +/- 19 g vs 87.6 +/- 4.2 g, p < 0.05 vs TPN respectively). Sponge OHP content on day 5 was significantly higher in the ENT group (101 +/- 3 vs 86.7+/-5.8 microg/100 sponge, p < 0.05). These data demonstrate that the enteral feeding route imparts a benefit to early post-traumatic wound healing s compared to parenteral feeding.     

Wound shape geometry measurements correlate to eventual wound healing

Wound geometry measurements have long been associated with wound-healing outcomes but there is little published evidence to support this. We studied serial wound tracings of 338 venous leg ulcers (VLUs) that had been followed during a controlled, prospective, randomized pivotal trial of two topical wound treatments, to determine whether the relationship between wound surface area and wound perimeter planimetry measurements, as well as the qualitative assessment of wound shape, could be correlated to wound-healing outcomes. VLUs that transitioned to a more convex wound shape, and maintained a linear relationship between their wound margin size and wound surface area size, had faster healing rates and were more likely to completely heal by 12 weeks (odds ratio=4.84, p =0.001). VLUs that initially presented with isolated areas of epithelium within the wound margins, large concavities, or were segmented into multiple ulcers typically had a poorer linear correlation between their margins and their surface area. Only 18 out of 134 (13%) VLUs with a linear r ²<0.80 eventually reached full wound closure, vs. 43% (102 of 270) of the remaining wounds with an r ²≥0.80 (Fisher's exact p <0.001). We believe our results show that the proportional relationship between one-dimensional perimeter and area measurements accurately correlates to the healing progress of the wound. Wounds that do not correlate to this linear relationship (concave geometries or multiple islands of healing) may be physiologically different than wounds that have good linear correlation, which we concluded through the analysis of wound acetate tracings.     

Outcome measurements in wound healing are not inclusive: a way forward

Standardized outcome measurement in wound healing has been an elusive goal. Whilst research into wound healing science and technology continues to progress rapidly, the lack of a uniform outcome assessment is making comparative analysis of results difficult. This paper seeks to outline the reported clinical, physiological, and histological outcomes that have been utilized in the literature. A minimal data set base for wound outcome evaluation is also established to be validated by future multivariate analysis of patient data.     

Laser skin welding: in vivo tensile strength and wound healing results

BACKGROUND AND OBJECTIVE: Laser skin welding was investigated as a general model for laser tissue closure. Scanned delivery of near-infrared laser radiation in combination with a dye can produce strong welds with limited thermal damage. STUDY DESIGN/MATERIALS AND METHODS: Two-centimeter-long, full-thickness incisions were made on the backs of guinea pigs. Wounds were closed either by laser welding or sutures and then biopsied at 0, 3, 6, 10, 14, 21, and 28 days postoperatively. Welding was achieved by using continuous-wave, 1. 06-micrometer, Nd:YAG laser radiation scanned over the incisions to produce a dwell time of approximately 80 msec. The cooling time between scans was fixed at 8 seconds. A 4-mm-diameter laser spot was maintained during the experiments, and the power was kept constant at 10 W. The operation time was fixed at 10 minutes per incision. India ink was used as an absorber of the laser radiation at the weld site, and clamps were used temporarily to appose the incision edges. RESULTS: Acute weld strengths of 2.1 +/- 0.7 kg/cm(2) were significantly higher than suture apposition strengths of 0.4 +/- 0.1 kg/cm(2) (P < 0.01), and weld strengths continued to increase over time. Lateral thermal damage in the laser welds was limited to 200 +/- 40 micrometer near the epidermal surface with less thermal damage deeper within the dermis. CONCLUSION: Our welding technique produced higher weld strengths and less thermal damage than reported in previous skin welding studies and may represent an alternative to sutures.     

Early healing rates and wound area measurements are reliable predictors of later complete wound closure

This study was undertaken to determine if healing rates are reliable early predictors of ultimate complete wound closure in venous leg ulcers and diabetic foot wounds. We conducted a retrospective analysis of 306 venous leg ulcers and 241 diabetic foot ulcers enrolled in two large controlled, prospective, randomized pivotal trials to compare topical wound treatments, to determine whether certain early markers of healing could be correlated with later total wound closure. Two-sided tests at 95% confidence demonstrated that wound margin advance, initial healing rate, percent wound surface area reduction, and wound healing trajectories (all p <0.001) were powerful predictors of complete wound healing at 12 weeks. Wounds with poor healing progress by these criteria at 4 weeks were highly likely to remain unhealed after 8 additional weeks of treatment. Analysis of the diabetic foot ulcers and venous leg ulcers subgroups separately demonstrated consistent statistical test results with high significance; similarly, the results remained valid independent of the topical treatment used. The early prediction of eventual wound healing or nonhealing using early healing rates may enable more efficient triage of patients to advanced healing technologies. We believe that these surrogate markers are robust predictors of healing regardless of wound etiology and that they merit wider use in clinical trials and routine patient care.     

Inflammation and wound healing: the role of bacteria in the immuno-regulation of wound healing

Wound healing is a sequence of complex events, an imbalance of which can result in a failure of the wound to heal, with significant implications for patients and health care services alike. Although the exact mechanism that underlies these events is not fully understood, inflammatory processes and the innate immune system play a vital role, not only in normal wound healing but also in the pathophysiology of delayed wound healing. These defense mechanisms are affected by underlying disease states and medical conditions, for example, diabetes, venous insufficiency, and the inflammation associated with acute trauma. Importantly, however, these processes are also modulated in health by bacteria within the wound. This article examines the role of the mediators of inflammation involved in the wound-healing process and discusses the function of these mediators when normal healing fails. The reaction of the wound to bacterial contamination and the effect of bacteria on wound healing are also discussed.     

Acute wound healing: the biology of acute wound failure

Acute wound healing failure is an important source of morbidity and mortality for surgical patients. Many incisional hernias, gastrointestinal anastomotic leaks, and vascular pseudoaneurysms occur despite patient optimization and standardized surgical technique. Modern surgical experience suggests that biologic and mechanical pathways overlap during "normal" acute wound healing. The cellular and molecular processes activated to repair tissue from the moment of injury are under the control of biologic and mechanical signals. Successful acute wound healing occurs when a dynamic balance is met between the loads placed across a provisional matrix and the feedback and feed-forward responses of repair cells.     

Fetal wound healing: an overview

The ability of fetal tissues to heal without scarring has prompted extensive research into the biochemical and molecular differences between fetal and postnatal wound healing. A thorough understanding of the basic mechanisms of fetal wound repair may to lead to approaches to correct or prevent the clinical problems encountered in abnormal adult wound healing and fetal surgery. This article contrasts the normal healing response in adults with fetal repair in animal models, highlighting investigations of extracellular matrix expression, cytokine profiles, and cellular dynamics.     

Disorders of wound healing

The healing wound offers a variety of potential end results. The surgeon's responsibility is to define what he wants and then arrange to get it. History has proved that technical improvements can eliminate disorders such as dehiscence and incisional hernias. Technical improvements should diminish the frequency of failed tendon repairs. When the author first became interested in wound healing and was asked to consult about a poorly healing wound, he could only offer the ideas that ascorbic acid might be given and that nutrition in some nonspecific way might be increased. Now, it is an unusual wound that cannot be made to heal in one way or another; wounds that cannot be made to heal are almost always a result of severe regional ischemia with or without osteoradionecrosis. Even moderately severe osteoradionecrosis can now be expected to heal by supplying the major deficiency consequent upon vascular damage by radiation, namely, oxygen (by hyperbaric administration). Perhaps most important to the surgeon is the knowledge that many kinds of disordered repair can be avoided. Liver disease can be treated, steroid hormone excess can be corrected or specifically treated with vitamin A, and nutritional defects can be anticipated and avoided. Familial tendencies to scar formation can be thwarted at an earlier rather than later, often hopeless, stage. Burn contractions in particularly susceptible joints can be anticipated and prevented by splinting and traction. In fact, we are coming very close to having effective treatment for most of the recognizable postsurgical reparative disorders. What we do not have is a prevention or cure for a vast variety of conditions of excessive repair, conditions that surgeons do not ordinarily recognize as complications. A vast amount of human misery is due to hypertrophic scar formation in arteries (arteriosclerosis), joints (arthritis), and ocular disease, especially those involving the scarring of the cornea. It is very likely that the surgeons will contribute to the prevention and cure of these disorders if they will accept the view that they can expect something close to perfection in any wound they make.