Rodney K. Chan

Ischaemia–reperfusion is an event triggered by immune complexes and complement

Reperfusion injury is a common clinical problem that lacks effective therapy. Two decades of research implicating oxygen free radicals and neutrophils has not led to a single successful clinical trial.

The Differing Roles of the Classical and Mannose-Binding Lectin Complement Pathways in the Events following Skeletal Muscle Ischemia-Reperfusion

Complement is an important mediator of the injuries observed after skeletal muscle ischemia and subsequent reperfusion. Although the classical pathway had been assumed to be the major pathway of activation leading to injury, the mannose-binding lectin (MBL) pathway might also play a contributing role. In this study, we found that MBL-deficient mice had significant protection after skeletal muscle reperfusion injury compared with wild-type, classical pathway-specific C1q-deficient mice, or MBL-deficient mice reconstituted with recombinant human MBL. MBL-deficient mice, however, were not protected from permeability edema or secondary lung injury after ischemia-reperfusion. These data indicate that blockade of the classical pathway alone (C1q) is protective against permeability edema and remote pulmonary injury but not protective against histologic muscle injury. In contrast, blocking the MBL pathway alone protects against histological injury but is not protective against permeability edema or lung injury. Thus, the activation of both pathways is likely responsible for the full spectrum of injuries observed after skeletal muscle reperfusion injury.

Healing modulation induced by freeze-dried platelet-rich plasma and micronized allogenic dermis in a diabetic wound model

The incidence and prevalence of chronic and diabetic wounds are increasing and clinical treatments to tackle these epidemics are still insufficient. In this study, we tested the ability of freeze‐dried platelet‐rich plasma (PRP) and an allogenic micronized acellular dermal matrix alone and in combination to modulate diabetic wound healing. Therapeutic materials were applied to 1.0u2003cm2 excisional wounds on genetically diabetic (db/db) mice. Wound‐healing kinetics and new tissue formation were studied at 9 and 21 days posttreatment. Quantitative immunohistochemistry was used to study vascularity and cellular proliferation (days 9 and 21), and collagen deposition was evaluated 21 days postwounding. In vitro, micronized allogenic dermis, when combined with PRP, absorbed nearly 50% of original platelet‐derived growth factor, transforming growth factor‐β, vascular endothelial growth factor, and epidermal growth factor from platelets and stimulated fibroblast proliferation. In vivo, micronized dermis increased the formation of vascularized wound tissue by day 9. Freeze‐dried PRP alone or in combination with micronized dermis increased wound tissue revascularization and proliferation compared with spontaneous healing. The increase in cell proliferation persisted until day 21 only when freeze‐dried PRP was used in combination with micronized dermis. These results indicate that micronized allogenic dermis may be used to provide a dermal matrix to stimulate tissue formation and the combination with PRP may confer additional beneficial growth factors to chronic or diabetic wounds.

Effect of Recombinant Platelet-Derived Growth Factor (Regranex®) on Wound Closure in Genetically Diabetic Mice

Burns, especially those involving large surface areas, represent a complex wound healing problem. Platelet-derived growth factor (PDGF) is released by activated platelets to recruit inflammatory cells toward the wound bed. It has effects on promoting angiogenesis and granulation tissue formation. However, the effectiveness of topical PDGF on wound closure is variable, ranging from little improvement observed in pig models to dramatic improvement reported in a diabetic mouse model. Here, we sought to determine the effectiveness of commercially sold PDGF-BB (Regranex®) on wound closure in genetically diabetic mice. C57BL/KsJ db+/db+ mice and its host strain bearing dorsal 1.5-cm2 wounds were divided into groups (n = 8 in each group) receiving topical application of either Regranex® (10 &mgr;g/wound) or vehicle for 5 consecutive days after wounding. The rate of wound closure was analyzed using computerized planimetry. The amount of granulation tissue was determined histologically. Our data indicate that diabetic mice exhibit a significant delay in wound closure when compared with their host strain. Topical application of Regranex® did not improve the time to wound closure but did significantly increase the amount of granulation tissue. Our current study using commercially available Regranex® failed to reproduce the previously reported finding that PDGF improved wound closure in healing impaired genetically diabetic mice.

Predictors of survival and length of stay in burn patients older than 80 years of age: does age really matter?

Predictors of survival and length of stay (LOS) in the advanced elderly with burn injuries is not well studied. Because of progress in burn wound and critical care, we hypothesized that a contemporary analysis would show improved outcomes. Clinical data were collected on 45 consecutive patients older than 80 years of age that were treated for burn injury at our institution during the past 10 years. Regression analysis was used to identify predictors of LOS and survival. Overall rate of mortality was 29%, and no patient survived a burn more than 60% TBSA. The strongest predictor of survival was percent TBSA burn. LOS of survivors was dependent on presence of inhalation injury and total number of operations. The survival of patients older than 80 years of age with burn injury is better than reported. Modern burn care allows survival in many patients over 80 with less than 60% TBSA burns without significant other co-morbidities.

Side population hematopoietic stem cells promote wound healing in diabetic mice

Background: Early evidence suggests that stem cells play a role in normal wound healing. Various impaired wound-healing states might be due to a deficiency in the stem cell repertoire. The authors sought to demonstrate that a new subset of lymphoid progenitor murine hematopoietic stem cells will accelerate wound healing in diabetic mice. Methods: Bone marrow cells were harvested from C57Bl6/J femurs and separated into side and main populations based on their ability to efflux the vital dye Hoechst 33342 and the presence or absence of CD7 and CD34 markers. Side or main population cells and control solution were applied once topically to 1-cm2 full-thickness dorsal excisional wounds in lepr db/db and wild-type mice on the day after wounding (n = 12 in each group). Wound closure was followed by computer planimetry. Wounds were harvested after 7 and 25 days for histological analysis. Results: Topical side population treatment had a significant effect on wound closure in diabetic animals, with a higher percentage of wound closure (35 ± 7.2 percent) in this group on postoperative day 7 compared with animals treated with either main population cells (16 ± 4.9 percent) or a vehicle control using saline (14 ± 6.7 percent) (p < 0.05). When side population cells were given to wild-type mice that already had a normal stem cell repertoire, there was a trend toward better wound closure, but no significant differences were found. Conclusions: Side population–treated wounds healed more quickly than main population–or control-treated wounds in diabetic mice, suggesting that one stem cell subpopulation, but not the majority, harbors the potential for improving the healing process. Further studies are needed to investigate the mechanism of healing and to explore its potential as a therapeutic agent.

Controlled induction of distributed microdeformation in wounded tissue via a microchamber array dressing

Mechanical stimuli are known to play an important role in determining the structure and function of living cells and tissues. Recent studies have highlighted the role of mechanical signals in mammalian dermal wound healing. However, the biological link between mechanical stimulation of wounded tissue and the subsequent cellular response has not been fully determined. The capacity for researchers to study this link is partially limited by the lack of instrumentation capable of applying controlled mechanical stimuli to wounded tissue. The studies outlined here tested the hypothesis that it was possible to control the magnitude of induced wound tissue deformation using a microfabricated dressing composed of an array of open-faced, hexagonally shaped microchambers rendered in a patch of silicone rubber. By connecting the dressing to a single vacuum source, the underlying wounded tissue was drawn up into each of the microchambers, thereby inducing tissue deformation. For these studies, the dressings were applied to full-thickness murine dermal wounds with 200 mmHg vacuum for 12 h. These studies demonstrated that the dressing was capable of inducing wound tissue deformation with values ranging from 11 to 29%. Through statistical analysis, the magnitude of the induced deformation was shown to be a function of both microchamber height and width. These results demonstrated that the dressing was capable of controlling the amount of deformation imparted in the underlying tissue. By allowing the application of mechanical stimulation with varying intensities, such a dressing will enable the performance of sophisticated mechanobiology studies in dermal wound healing.

Use of Previously Burnt Skin in Local Fasciocutaneous Flaps

Reconstruction of severe burns in patients remains a challenge. This is particularly problematic in wounds that require durable flap coverage such as exposed bony prominences, tendons, and joints due to the paucity of normal adjacent skin donor sites. Reluctance in using local or regional flaps previously burned or skin-grafted is based on the erroneous assumption of inferior blood supply in the burned skin from prior thermal damage. The initial thermal injury is generally limited to the skin and subcutaneous fat; the underlying fascia and its vasculature are usually spared.