Simon Myers

The role of hyaluronic acid in wound healing: assessment of clinical evidence.

Hyaluronic acid (hyaluronan), a naturally occurring polymer within the skin, has been extensively studied since its discovery in 1934. It has been used in a wide range of medical fields as diverse as orthopedics and cosmetic surgery, but it is in tissue engineering that it has been primarily advanced for treatment. The breakdown products of this large macromolecule have a range of properties that lend it specifically to this setting and also to the field of wound healing. It is non-antigenic and may be manufactured in a number of forms, ranging from gels to sheets of solid material through to lightly woven meshes. Epidermal engraftment is superior to most of the available biotechnologies and, as such, the material shows great promise in both animal and clinical studies of tissue engineering. Ongoing work centers around the ability of the molecule to enhance angiogenesis and the conversion of chronic wounds into acute wounds.

A hyaluronic acid membrane delivery system for cultured keratinocytes : Clinical take rates in the porcine kerato-dermal model

The clinical take rates of cultured keratinocyte autografts are poor on a full-thickness wound unless a dermal bed is provided. Even under these circumstances two important problems are the time delay in growing autografts and the fragility of the grafts. A laser-perforated hyaluronic acid membrane delivery system allows grafting at early confluence without requiring dispase digestion to release grafts from their culture dishes. We designed this study to investigate the influence of this membrane on clinical take rates in an established porcine kerato-dermal grafting model. The study demonstrated a significant reduction in take as a result of halving the keratinocyte seeding density onto the membrane. The take rates, however, of grafts grown on the membrane at half or full conventional seeding density and transplanted to a dermal wound bed were comparable, if not better, than those of keratinocyte sheet grafts.

Culturing skin in vitro for wound therapy

Current tissue-culture techniques enable keratinocytes from a small piece of skin to be grown into sheets of epithelium, or cultured keratinocyte grafts, that are suitable for treating wounds. Serial subculture enables rapid expansion of a cell population, such that grafts of a total area equivalent to that of the surface of an adult can be obtained from an initial skin biopsy of approximately 2 cm2 in under one month. In this article, the methods currently used for culturing keratinocytes, the search for a fully functional replacement for the dermal elements of skin, and the prospects for clinical development of these technologies in the near future are discussed.

Three- and four-dimensional computed tomography angiographic studies of commonly used abdominal flaps in breast reconstruction.

Background: The innovative technique of three- and four-dimensional computed tomographic angiography allows us to analyze the areas of perfusion in commonly used free abdominal flaps in breast reconstruction, such as pedicled transverse rectus abdominis musculocutaneous (TRAM) flaps, full TRAMs, muscle-sparing TRAMs, and deep inferior epigastric perforator (DIEP) flaps. The authors compared the vascular territories in these flaps. Methods: A total of 11 lower abdominal flaps were obtained from nine cadavers and two abdominoplasty procedures. The authors simulated the perfusion of seven pedicled TRAMs, eight full TRAMs, eight muscle-sparing TRAMs, 14 DIEPs, and six superficial inferior epigastric artery flaps. For each simulated flap, the named artery/perforator was injected with Omnipaque contrast using a Harvard precision pump at 0.5 ml/minute, and the flap was subjected to dynamic computed tomographic scanning using a GE Lightspeed 16-slice scanner. Scans were repeated at 0.125-ml increments (every 15 seconds) for the first 1 ml, then at 0.5-ml increments (every 60 seconds) for the next 2 to 3 ml, thus giving progressive computed tomographic images over time. Images were viewed using both General Electrics and TeraRecon systems, allowing analysis of branching patterns and perfusion flow as well as measurements of vascular territory. Conclusions: This study shows that there are definitive differences in vascular territory based on flap type. The sequences of images also allow us to reappraise the classic Hartrampf zones of perfusion.

Three- and Four-Dimensional Arterial and Venous Perforasomes of the Internal Mammary Artery Perforator Flap

Background: The internal mammary artery perforator flap has been used in head and neck reconstruction. Although anatomical and perfusion studies with ink have been performed previously, the authors now use three- and four-dimensional computed tomographic angiography to precisely visualize vascular anatomy of individual perforators (perforasomes) and the axiality of perfusion. Methods: Eleven hemichest adipocutaneous flaps were dissected from cadavers. Measurements were recorded, such as the distance of each internal mammary artery perforator from the sternal edge, diameter of vessels, and number and location of internal mammary artery perforators per hemichest. Single internal mammary artery perforator injections with Isovue contrast were carried out, and the flaps were subjected to dynamic computed tomographic scanning. Static computed tomographic scanning was also undertaken using a barium-gelatin mixture. Images were viewed using both General Electric and TeraRecon systems, allowing the appreciation of vascular territory (three-dimensional), and analysis of perfusion flow (four-dimensional). Results: Each hemichest flap had one to three internal mammary artery perforators, most commonly in intercostal spaces 1, 2, and 3. Twenty-six internal mammary artery perforators were dissected, and 19 perforator arteries and six perforator veins were injected with contrast. The internal mammary artery perforator in the second intercostal space had the largest mean diameter and a large vascular territory. Linking vessels, both direct and indirect, communicate between perforators and can enlarge perforasomes. Linking vessels were also found between internal mammary artery perforators and the lateral thoracic artery. Conclusions: Three- and four-dimensional computed tomographic angiography allows detailed analysis of vascular anatomy. Important information such as internal mammary artery perforator flap dimensions, linking vessels, and axiality of perfusion is elucidated, thus contributing to a better understanding of perforator flaps.

Patient-related keloid scar assessment and outcome measures

Background: Keloid scars cause pain, itching, functional limitation, and disfigurement, leading to psychological distress. Progress in treatment regimens is hindered by the lack of a universally accepted outcome measure. The Patient and Observer Scar Assessment Scale is a tool for the assessment of scars, incorporating an assessment by both clinician and patient. This study evaluates its application to keloids and compares it to the widely used Vancouver Scar Scale, which is considered the standard mode of assessment for scars. Methods: Three observers using the two scales assessed 34 patients with 41 keloid scars independently. Patients evaluated their own scars simultaneously using the patient component of the Patient and Observer Scar Assessment Scale. Internal consistency, interobserver reliability, and convergent validity were examined. Results: Both components of the Patient and Observer Scar Assessment Scale had high internal consistency (0.82 and 0.86 for patient and observer components, respectively); those rates were higher than the rate for the Vancouver Scar Scale (0.65). Interobserver reliability was “substantial” for the Vancouver Scar Scale (0.65) and “almost perfect” for the observer component of the Patient and Observer Scar Assessment Scale (0.85). Convergent validity was very strong (0.83, p < 0.01), although the patient component did not correlate well with either of the observer scales. Patients rated their scars worse than the observer average for 83 percent of the scars, and were influenced by color, stiffness, thickness, and irregularity (p < 0.05). Conclusion: The findings support the use of the Patient and Observer Scar Assessment Scale as a reliable and valid method of assessing keloid scars in a clinical context. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

How far can a juxtacrine signal travel

Juxtacrine signalling is the process of cell communication in which ligand and receptors are both anchored in the cell membrane. We develop three mathematical models for this process, involving different mathematical representations of the dynamics of membrane–bound ligand and free and bound receptors, within an epithelial sheet. We consider the dynamics of this system following a localised disturbance, such as would be provided by a source of ligand or by the generation of a free edge via wounding. We study the ability of the juxtacrine mechanism to transmit a signal away from this disturbance, and show analytically that the spatial half–life of the signal can in fact be arbitrarily large. This result is quite general, since we use a generic reaction kinetic scheme; the key assumption is that ligand and receptor production are both upregulated by binding. Moreover, the result applies to all three of our model formulations. We conclude by discussing applications of the result to the particular case of the transforming growth factor alpha binding to epidermal growth factor receptor in epidermal wound healing.

Assessment of microsurgery competency-where are we now?

In the last decade surgical training is being revolutionized by two novel concepts that have been introduced to almost all branches of surgery including and most recently to microsurgery. These two concepts are: objective assessments of surgical skills and the nurturing of surgical skills in a simulation laboratory setting. Acquiring surgical skills in the laboratory setting can help move the microsurgical learning curve from the patient to the laboratory and this will in turn improve patient safety. In order to optimize microsurgical training through a competency based training programme, it is imperative for microsurgical educators to understand microsurgical skill acquisition. This requires accurate objective assessment tools that can define and quantify microsurgical competency. This article aims to review the current literature on the various objective assessment tools adapted for microsurgery and attempt to identify the gaps that need to be addressed by research in microsurgical education to establish the ideal objective assessment tool.

A systematic review of evidence for education and training interventions in microsurgery.

Over the past decade, driven by advances in educational theory and pressures for efficiency in the clinical environment, there has been a shift in surgical education and training towards enhanced simulation training. Microsurgery is a technical skill with a steep competency learning curve on which the clinical outcome greatly depends. This paper investigates the evidence for educational and training interventions of traditional microsurgical skills courses in order to establish the best evidence practice in education and training and curriculum design. A systematic review of MEDLINE, EMBASE, and PubMed databases was performed to identify randomized control trials looking at educational and training interventions that objectively improved microsurgical skill acquisition, and these were critically appraised using the BestBETs group methodology. The databases search yielded 1,148, 1,460, and 2,277 citations respectively. These were then further limited to randomized controlled trials from which abstract reviews reduced the number to 5 relevant randomised controlled clinical trials. The best evidence supported a laboratory based low fidelity model microsurgical skills curriculum. There was strong evidence that technical skills acquired on low fidelity models transfers to improved performance on higher fidelity human cadaver models and that self directed practice leads to improved technical performance. Although there is significant paucity in the literature to support current microsurgical education and training practices, simulated training on low fidelity models in microsurgery is an effective intervention that leads to acquisition of transferable skills and improved technical performance. Further research to identify educational interventions associated with accelerated skill acquisition is required.

Epidermal repair results from activation of follicular and epidermal progenitor keratinocytes mediated by a growth factor cascade

Reepithelialization of human suction blister wounds was examined in five normal human volunteers over a period of 14 days postwounding to understand the control of keratinocyte migration, proliferation, and differentiation in acute wound healing in a controlled model. The hypothesis that morphological changes and progenitor activation result from altered cytokines and growth factor expression [in particular interleukin‐1 β (IL‐1β), interleukin‐6 (IL‐6), transforming growth factor α (TGF‐α), TGF‐β 1, and keratinocyte growth factor] was tested using semiquantitative immunohistochemistry combined with reverse transcriptase‐polymerase chain reaction of samples from the blister roof, edge, and base. Parallel changes in keratin expression were examined using a wide range of well‐established antibodies to multiple keratins and in situ hybridization for keratin 16 (K16), a marker of the hyperproliferative (mucoregenerative) phenotype. Longitudinal morphological, semiquantitative cytokine and growth factor expression, and histometric histone and cytokeratin profiles suggest three phases to reepithelialization: phase 1, or the acute activation phase, early in the first 24 hours postwounding is characterized by epidermal expression of IL‐1β and IL‐6, and dermal expression of TGF‐β1, as basal, upper outer root sheath, and putative interfollicular transit amplifying keratinocytes become committed to mitosis; phase 2, or the early activation phase, late in the second 24 hours postwounding, characterized by epidermal expression of TGF‐α and IL‐6 with concurrent suprabasal K16 expression and migration with continued proliferation, and dermal expression of keratinocyte growth factor and IL‐6; and phase 3 or restitution over the following 2 weeks, characterized by the return of normal homeostasis, including bulge activation as evidenced by K19 expression.