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|Title:||An innovative assessment of the biomechanical properties of plantar tissues and diabetic foot ulcers||Authors:||Chao, Yuet Lan Clare||Degree:||Ph.D.||Issue Date:||2012||Abstract:||Foot ulcers are a common complication of diabetes mellitus and the predisposing factors are multifactorial. Diabetic peripheral neuropathy and repetitive stress are the most well known causative factors for diabetic related foot injuries while microvascular dysfunction is throught to be an essential factor contributing to the pathogenesis of tissue breakdown in the diabetic foot. It may also play a role in the development of neuropathy and interact with the complex interchange of advanced glycosylation end products as induced by hyperglycaemia, causing potential pathological consequences of morphological change in skin and soft tissue properties. Yet the precise mechanism of this process remains unclear. Apart from the pathological changes that take place in plantar skin morphology, foot swelling and changes in the properties of plantar soft tissues may further increase the risk of foot ulceration in people with diabetes. In order to develop strategies to prevent or manage diabetic ulcers, it is vital to obtain a better understanding of the underlying pathophysiology of diabetic ulcers. Also, a precise and quantitative method for evaluating the healing of ulcers is essential for making appropriate treatment decisions and monitoring the efficacy of the treatments. Thus far, a precise quantitative method of assessing wound healing or the properties of ulcer tissues is lacking. The restoration of the mechanical properties of wound tissue is an important indicator of the quality of wound healing. Nonetheless, changes in the biomechanical properties of skin wound tissues across different phases of the wound healing process have not been explored. In laboratory work, the evaluation of wound tissue properties can be achieved by testing an excised wound specimen using Material Testing Systems in vitro. An optical coherence tomography (OCT)-based air-jet indentation system is a novel non-contact method that has been recently developed for characterizing the biomechanical properties of soft tissues in a non-contact way. It can potentially be used for assessing the properties of wound tissues in vivo. This project consists of four inter-related studies, with each study having specific objectives. They are: (I) The epidermal thickness and biomechanical properties of plantar tissues in the diabetic foot; (II) The association between skin blood flow and oedema on epidermal thickness in the diabetic foot; (III) A novel non-contact method to assess the biomechanical properties of wound tissue in humans; (IV) In vivo and in vitro approaches to studying the biomechanical properties of healing wounds in rat skin.
Study I: The objective of Study I was to examine the morphological changes in plantar epidermal thickness and in the properties of the soft tissues of the diabetic foot in humans. Method and result of Study I: Seventy-two people with diabetes, namely 22 people with neuropathies, 16 with foot ulcerations, 34 with diabetics but without complications; and 40 healthy controls participated in the study. The thickness of the epidermal layer of the plantar skin was examined using high-frequency ultrasonography. Using the Tissue Ultrasound Palpation System, the thickness and stiffness of the total plantar soft tissue were measured at the big toe, the first, third, and fifth metatarsal heads, and the heel pad. As compared with the control group, the average epidermal thickness of plantar skin decreased by 15% in people with diabetic foot ulcerations and 9% in people with neuropathy, but increased by 6% in those with diabetes without complications. An 8% increase in the total thickness of the plantar soft tissues was observed in all diabetic subjects at all testing sites (all p<0.05), with the exception of the first metatarsal head. The stiffness of the plantar soft tissues increased in all diabetic groups at all testing sites as compared with the control group (all p<0.05). Study II: The aim of this study was to explore the association of skin blood flow and oedema on epidermal thickness in the feet of people with and without diabetes. Eighty-seven subjects, namely 19 people with diabetic neuropathy and foot ulcerations, 35 people with diabetes but without neuropathy, and 33 non-diabetic healthy controls participated in the study. High-frequency ultrasonography was used to measure the epidermal thickness and oedema in the papillary skin of the big toe as reflected by the thickness of the subepidermal low echogenic band (SLEB). The capillary nutritive blood flow was measured by the use of video capillaroscopy and skin blood flux was monitored by laser-Doppler flowmetry. We demonstrated that the thickness of the SLEB had increased in all diabetics, to a greater extent in people with neuropathy and ulceration than those without (64.7% vs 11.8%, p<0.001). Skin blood flux was shown to be higher in the groups with diabetes than in the controls (all p<0.05), but no significant difference was found in the resting nutritive capillary blood flow (p>0.05). A significant fair negative correlation (p=0.002, r=-0.366) was demonstrated between the SLEB and epidermal thickness at the pulp of the big toe, while no significant correlations were found among capillary blood flow, skin blood flux, and epidermal thickness (all p>0.05). Study III: This study evaluated the stiffness of diabetic foot ulcer tissues and examined the test-retest reliability of the newly developed OCT-based air-jet indentation system for characterizing the biomechanical properties of wound tissues in humans. Eight subjects with diabetes (7 males, 1 female) participated in the study, and a total of 10 foot ulcers were assessed. Twenty measuring sites located either at the central wound bed (n=10) or in periulcer areas (n=10) were identified and their biomechanical properties were assessed by the use of the air-jet indentation system. The test-retest reliability was examined at all measuring points. We found that the average stiffness of the peri-ulcer area (0.47 ± 0.15 N/mm) was significantly higher than that of the central wound bed area (0.35 ± 0.23 N/mm; p=0.042). Excellent test/retest reliability was demonstrated (ICC: 0.986; Pearson’s correlation: r=0.972, p<0.001). Study IV: This study examined the biomechanical properties of healing skin wounds in vivo using an air-jet indentation system and in vitro using a conventional material testing system in a rat model. Thirty male Sprague-Dawley rats, each with a 6 mm full-thickness circular punch biopsied wound at each posterior hind limb, were used. The stiffness at both the wound central and the margins was measured repeatedly in five rats at the same wound sites to monitor the longitudinal changes over various wound healing phases (i.e., before wounding, and on Days 0, 3, 7, 10, 14, and 21 after wounding) in vivo using an OCT-based air-jet indentation system. In addition, five rats were euthanized at each time point, and the biomechanical properties of the wound tissues were assessed in vitro using a material testing system. The size of the wound shrank significantly in the initial few days, closing almost completely by Day 10. At the central wound bed region, the stiffness at the baseline pre-wounding stage was 16.9 ± 2.2 N/m, which increased significantly from Day 0 (19.8 ± 5.3 N/m, 17.16%) and reached its peak on Day 7 (52.1 ± 20.6 N/m, 208.28%), but then progressively decreased until Day 21 (23.7 ± 3.2 N/m, 40.24%). In contrast, the biomechanical parameters of skin wound tissue measured by the material testing system showed a marked reduction upon wounding, and then gradually increased with time (all p<0.05). On Day 21, the ultimate tensile strength and stress of the skin wound tissue was about 50% of that of the unwounded skin; whereas the stiffness of the tissue recovered at a faster rate, reaching 97% of the pre-wounding status by Day 21. Overall, the present thesis demonstrated that for people with diabetes, particularly for those with neuropathy or ulceration, the epidermal plantar skin became thinner and the plantar soft tissues stiffened. In addition, an increase in subepidermal oedema was demonstrated in people with diabetic neuropathy and ulceration, which may partly contribute to a reduction in epidermal thickness at the pulp of the big toe. All of these changes may subsequently lead to the breaking down of skin in the diabetic foot. This implies that diabetes-associated changes in the biomechanical properties of plantar skin, plantar soft tissues, and foot swelling are potential risk factors of foot ulceration in people with diabetes. Therefore, regular examinations of the sole of the foot of people with diabetes and the wearing of proper shoes should be reinforced in order to prevent foot complications. As for the stiffness of diabetic foot ulcer tissues, we demonstrated that the peri-ulcer area was stiffer than the ulcerated tissues in a diabetic foot with ulcers. This greater magnitude of hardness and inelasticity in the peri-ulcer region may scatter some of the contractile forces for wound contraction during the healing process. The newly developed OCT-based air-jet indentation system is a reliable tool for characterizing the stiffness of soft tissues around the wound in a non-contact way in vivo. As for the changes in the biomechanical properties of skin wound tissues across different phases of the wound healing process, we found that stiffness recovered at a faster rate than tensile strength in rat skin wounds that were healing. Measurements made by the air-jet-indentation system and by the material testing systems involve different principles, but both systems can reflect the biomechanical properties of wound tissue.
|Subjects:||Tissues -- Analysis.
Foot -- Ulcers.
Diabetes -- Complications.
Hong Kong Polytechnic University -- Dissertations
|Pages:||xxi, 609 p. : ill. (some col.) ; 30 cm.|
|Appears in Collections:||Thesis|
View full-text via https://theses.lib.polyu.edu.hk/handle/200/6770
Citations as of May 22, 2022
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