Regeneration of the dermis does not occur spontaneously in the adult mammal. The epidermis is regenerated spontaneously provided there is a dermal substrate over which it can migrate. Certain highly porous, crosslinked collagen-glycosaminoglycan copolymers have induced partial morphogenesis of skin when seeded with dermal and epidermal cells and then grafted on standard, full-thickness skin wounds in the adult guinea pig. A mature epidermis and a nearly physiological dermis, which lacked hair follicles but was demonstrably different from scar, were regenerated over areas as large as 16 cm2. These chemical analogs of extracellular matrices were morphogenetically active provided that the average pore diameter ranged between 20 and 125 lsm, the resistance to degradation by collagenase exceeded a critical limit, and the density of autologous dermal and epidermal cells inoculated therein was >5 X 104 cells per cm2 of wound area. Unseeded copolymers with physical structures that were within these limits delayed the onset of wound contraction by about 10 days but did not eventually prevent it. Seeded copolymers not only delayed contraction but eventually arrested and reversed it while new skin was being regenerated. The data identify a model extracellular matrix that acts as if it were an insoluble growth factor with narrowly specified physicochemical structure, functioning as a transient basal lamina during'morphogenesis of skin.Throughout development, extracellular matrices (ECMs) are continuously being remodeled-i.e., synthesized, degraded, and resynthesized (1)(2)(3)(4)(5). Healing of a deep skin wound also requires remodeling of an ECM-the basal lamina (basement membrane) between the epidermis and the dermis (2). ECMs are largely insoluble and nondiffusible, and they confer stiffness and strength to multicellular systems (1, 2). During remodeling, the ECM necessarily suffers degradation of macromolecular chains, a process that dramatically reduces the insolubility of the ECM and impairs its role as mechanical reinforcement of a multicellular system undergoing development. It is not clear just how the resistance of the ECM to degradation affects its role during morphogenesis.In physical terms, ECMs can be described as macromolecular networks that are covalently crosslinked and are highly swollen in extracellular fluid. Accordingly, the physical structure of an ECM can be characterized initially by specifying the volume fraction 'of macromolecular components (swelling ratio), the average diameter of pores in the highly swollen network, the density ofcrosslinks tying chains to each other, and the degree of crystallinity present. This model leads to questions such as the following ones. Is it necessary for a developmentally active ECM to persist as an undegraded, crosslinked macromolecular network (and, therefore, remain insoluble and nondiffusible) over a critical time scale? Is it necessary for such an ECM to contain pores of a critical size? We have answered these questions in a preliminary way by use of we...
Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of
The mechanism of action of the Vacuum Assisted Closure Therapy (VAC; KCI, San Antonio, Texas), a recent novel innovation in the care of wounds, remains unknown. In vitro studies have revealed that cells allowed to stretch tend to divide and proliferate in the presence of soluble mitogens, whereas retracted cells remain quiescent. The authors hypothesize that application of micromechanical forces to wounds in vivo can promote wound healing through this cell shape-dependent, mechanical control mechanism. The authors created a computer model (finite element) of a wound and simulated VAC application. Finite element modeling is commonly used to engineer complex systems by breaking them down into simple discrete elements. In this model, the authors altered the pressure, pore diameter, and pore volume fraction to study the effects of vacuum-induced material deformations. The authors compared the morphology of deformation of this wound model with histologic sections of wounds treated with the VAC. The finite element model showed that most elements stretched by VAC application experienced deformations of 5 to 20 percent strain, which are similar to in vitro strain levels shown to promote cellular proliferation. Importantly, the deformation predicted by the model also was similar in morphology to the surface undulations observed in histologic cross-sections of the wounds. The authors hypothesize that this tissue deformation stretches individual cells, thereby promoting proliferation in the wound microenvironment. The application of micromechanical forces may be a useful method with which to stimulate wound healing through promotion of cell division, angiogenesis, and local elaboration of growth factors. Finite element modeling of the VAC device is consistent with this mechanism of action.
Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided.
The efficacy of NPWT in promoting wound healing has been largely accepted by clinicians, yet the number of high-level clinical studies demonstrating its effectiveness is small and much more can be learned about the mechanisms of action. In the future, hopefully we will have the data to assist clinicians in selecting optimal parameters for specific wounds including interface material, waveform of suction application, and the amount of suction to be applied. Further investigation into specific interface coatings and instillation therapy are also needed. We believe that advances in mechanobiology, the science of wound healing, the understanding of biofilms, and advances in cell therapy will lead to better care for our patients.
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