Proper nutrition in presurgical patients can enhance wound healing and potentially decrease the cost of postsurgical medical care. Therefore, to combat increasing health care costs, it is important that the health care professional have a solid understanding of the role of essential nutrients in the healing process. The author reviews the role of the following in wound healing: protein, vitamin A, zinc, vitamin C, vitamin E, and iron.
The structure, classification, function, and regulation of matrix metalloproteinases in normal and abnormal wound healing is discussed. Results from key studies suggest that neutrophil-derived matrix metalloproteinase 8 (MMP-8) is the predominant collagenase present in normal healing wounds, and that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic leg ulcers. Excessive collagenolytic activity in these chronic wounds is possible because of the reduced levels of tissue inhibitor metalloproteinase 1 (TIMP-1). However, until recently, there have been no studies evaluating levels of matrix metalloproteinase or tissue inhibitors of metalloproteinase activity in chronic diabetic foot wounds. Improving basic knowledge and pharmaceutical intervention in this area ultimately may help clinicians identify and proactively intervene in an effort to prevent normal wounds from becoming chronic. This may prevent the high prevalence of morbidity associated with this significant health problem. (J Am Podiatr Med Assoc 92(1): 12-18, 2002)
Clinicians caring for chronic wounds can easily overlook nutritional status. Patients with diabetes are at high risk for primary and secondary malnutrition. Although profiles exist defining the extent of the deficiency, the process of wound healing and the interactions of the macronutrients and micronutrients necessary to accomplish it must first be understood. In elderly patients with diabetes, additional factors such as liver and renal function, the interdependence of the immune system, and protein synthesis, also must be considered. This article provides a practical format to assist clinicians in better evaluating this often difficult-to-assess area of care. (J Am Podiatr Med Assoc 92(1): 38-47, 2002)
We sought to develop new recombinant human epidermal growth factor (rhEGF)–containing hydrogels and to investigate their biological activity and therapeutic effects on wound healing in diabetic rats.
Levels of rhEGF released from hydrogels were measured by enzyme-linked immunosorbent assay. The cellular proliferating activity of released rhEGF was evaluated by MTT assay. Fifty-six wounded diabetic rats were randomly divided into four groups with different topical treatment daily. The therapeutic effects were evaluated by wound area measurement, histologic analysis, immunohistochemical assessment of proliferating cell nuclear antigen and B-cell lymphoma/leukemia-2, and Western blotting of EGF receptor.
The rhEGF released from the hydrogel matrix kept its bioactivity on stimulating proliferation of the BALB/c3T3 cell line. Wound closure rates on postoperative day 14 were 75.8% in the negative control group, 82.83% in the group treated with hydrogel matrix, 85.87% in the group treated with rhEGF-containing hydrogel, and 81.18% in the group treated with rhEGF solution. Compared with hydrogel matrix, rhEGF-containing hydrogel had an additional effect on induction of EGF receptor expression (P < .05). Compared with negative controls, protein expression of B-cell lymphoma/leukemia-2 was higher in the rhEGF-containing groups (P < .05). Proliferating cell nuclear antigen was induced at its highest level on day 7 in the rhEGF-containing hydrogel–treated group (P < .05).
These data from in vitro release and diabetic animal models highlight the efficacy of hydrogels as a controlled releasing system for topical application of EGFs. The rhEGF-containing hydrogel we developed holds the merits of prolonged and sustained releasing of bioactive rhEGF and therapeutic potential in enhancing diabetic wound healing. (J Am Podiatr Med Assoc 102(2): 89–98, 2012)
We sought to evaluate the relationship between baseline hemoglobin A1c (HbA1c) level and clinical outcomes, including foot ulcer outcome (resolved versus unresolved) and wound-healing time, in individuals with type 2 diabetes.
A prospective observational study was conducted on 99 patients presenting with a diabetic foot ulceration. Patient and ulcer characteristics were recorded. Patients were followed up for a maximum of 1 year.
After 1 year of follow-up, 77% of ulcers healed and 23% did not heal. Although this study demonstrated that the baseline HbA1c reading was not a significant predictor of foot ulcer outcome (P = .603, resolved versus amputated), on further statistical analyses, when HbA1c was compared with the time taken for complete ulcer healing in the resolved group (n = 77), it proved to be significant (P = .009).
These findings have important implications for clinical practice, especially in an outpatient setting. Improving glycemic control may improve ulcer outcomes. Prediction of outcome may be helpful for health-care professionals in individualizing and optimizing clinical assessment and management of patients. Identification of determinants of outcome could result in improved health outcomes, improved quality of life, and fewer diabetes-related foot complications.
Background: We investigated the mechanism of delayed would healing caused by diabetes and measured the dynamic changes in matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels. We noted differences in the ratio of MMP-9 to TIMP-1 in the wounds of diabetic and nondiabetic rats.
Methods: Forty-two Sprague-Dawley rats weighing 250 g were randomly assigned to either the control group or the streptozotocin-induced diabetes group. Then, full-thickness excision wounds were created on the middle of the back of each animal. Skin biopsy specimens were obtained on days 0, 3, 7, and 14 after incision. The content of collagen was quantified by Masson’s staining and the macrophage marker, and CD68 was detected by immunohistochemical analysis. Messenger RNA and protein expression of MMP-9 and TIMP-1 was measured by reverse transcriptase–polymerase chain reaction and Western blot, respectively.
Results: Diabetic rats exhibited slower wound healing than control animals (P < .05). On days 3, 7, and 14 after incision, higher levels of MMP-9 messenger RNA and protein expression were detected in the diabetic group compared with the control group (P < .05), and expression of TIMP-1 messenger RNA and protein was significantly decreased. In addition, the ratio of MMP-9 to TIMP-1 was stable in controls, whereas there was a marked increase in the ratio in diabetic skin wounds.
Conclusions: The balance between MMP-9 and its inhibitor, TIMP-1, is disturbed in diabetic skin tissue after injury, which may lead to histologic abnormality of diabetic skin and delayed wound healing. (J Am Podiatr Med Assoc 99(6): 489–496, 2009)
The relationship between hyperglycemia and adverse outcomes after surgery has been widely documented. Long-term glucose control has been recognized as a risk factor for postoperative complications. In the foot and ankle literature, long-term glycemic control as a potential perioperative risk factor is not well studied. Our goal was to investigate whether hemoglobin A1c (HbA1c) level was independently associated with postoperative complications in a retrospective cohort study.
Three hundred twenty-two patients with a diagnosis of diabetes mellitus were enrolled in the study to assess risk factors associated with postoperative foot and ankle surgery complications.
Bivariate analyses showed that HbA1c level and having at least one comorbidity were associated with postoperative infections. However, after adjusting for other covariates, the only significant factor was HbA1c level, with each increment of 1% increasing the odds of infection by a factor of 1.59 (95% confidence interval [CI], 1.28–1.99). For postoperative wound-healing complications, bivariate analyses showed that body mass index, having at least one comorbidity, and HbA1c level were significant factors. After adjusting for other covariates, the only significant factors for developing postoperative wound complications were having at least one comorbidity (odds ratio, 2.03; 95% CI, 1.22–3.37) and HbA1c level (each 1% increment) (odds ratio, 1.25; 95% CI, 1.02–1.53).
In this retrospective study, HbA1c level had the strongest association with postoperative foot and ankle surgery complications in patients with diabetes.
The influence of Aloe vera, orally and topically, on wound healing was studied. Wounds were induced on both sides of the vertebral column of ICR mice using a biopsy punch. For the oral study, experimental animals received A. vera in their drinking water for 2 months, whereas the control animals received only water. In the topical study, experimental animals were given 25% A. vera in Eucerin cream topically. The control animals received cream only. A 62.5% reduction in wound diameter was noted in mice receiving 100 mg/kg/day oral A. vera and a 50.8% reduction was recorded in animals receiving topical 25% A. vera. These data suggest that A. vera is effective by both oral and topical routes of administration.