Ulceration and Delayed Healing Following Pressure Loading in Hyperglycemic Rats With an Immature Dermal Collagen Fiber Network
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The collagen fiber network plays a key role regarding mechanical properties that maintain tissue shape, absorb stress, and recover from tissue deformation.The purpose of this study was to reveal the effects of hyperglycemia on the process of ulceration and wound healing, and on the structure of dermal collagen network. Methods. A spontaneous type 2 diabetic, non-obese rat without hyperlipidemia (GK rat) was used. On the right abdominal flank region, 8 kg/3 cm2 of pressure was loaded, and then the morphological change in wound area was macroscopically observed. The tissue of wounded area and healthy area on opposite side of the abdomen was collected and histologically analyzed on days 3, 5, 7, and 14 after wounding. Results. The hyperglycemic animals showed severer ulceration and delayed wound healing after pressure loading compared to control rats. The diabetic rat had an immature collagen fiber network with poor cross-linkage in the dermis. In the wounded area, collagen fibrils were packed more densely and reconstruction of the fiber network was delayed. Conclusion. These results suggest that the disrupted structure of the collagen network lowers the tolerance of diabetic skin to external pressure loading, and that this delayed reconstruction increases time to healing.
In both developed and developing countries around the world, changes in lifestyle have resulted in a dramatic increase in the incidence of chronic disease, particularly diabetes mellitus.1 The number of people suffering from diabetes mellitus is predicted to increase from the current estimate of 150 million to 220 million in 2010, and then to 300 million by 2025.2 In the clinical setting, patients with diabetes have a higher risk of developing pressure ulcers than people without diabetes.3 Patients with diabetes also often have delayed wound healing, which results in a prolonged treatment period.4,5 This phenomenon has become a significant problem that negatively affects quality of life for patients with diabetes and increases medical costs.
Generally, pressure ulcers are caused by a pressure force greater than capillary pressure, which thus induces tissue hypoxia, cell deformation, reperfusion, and ultimately, cell death.6 Collagen plays a key role in the mechanical properties acting to maintain tissue shape, absorb stress, and recover from tissue deformation. Collagen has a triple-strand coiled structure, which is termed tropocollagen. An aggregate of tropocollagen forms fibrils and bundled fibrils that develop into the thick, rope-like structure of collagen fiber.7 Extensive pressure loading results in irreversible changes in the structure of the collagen fiber network. Arao et al8 reported the densely packed fibrils in the boundary area and the disappearance of fibrous structure in the damaged area in comparison to the healthy area. The collagen network also plays various important roles, such as interacting with platelets and fibronectin, and forming a scaffold for fibroblastic proliferation during the wound healing process.9
The relationship between diabetes mellitus and cutaneous wound healing has been widely investigated. Loots et al10 reported that diabetic foot ulcer-derived dermal fibroblast showed delayed cell growth and abnormal morphology, a large dilated endoplasmic reticulum, and multiple lamellar and vesicular bodies.