Use of urea to stimulate healing in chronic purulent wounds

Urea has been found to stimulate healing in chronic purulent wounds. The effects obtained are a cleansing of the wound by the removal of necrotic material and pyogenic bacteria present, and a promotion of the growth of granulation tissue.     

Outcomes of allogenic acellular matrix therapy in treatment of diabetic foot wounds: an initial experience

The purpose of this study was to evaluate outcomes of persons with UT grade 2A neuropathic diabetic foot wounds treated with an acellular matrix. Data were abstracted for 17 consecutive patients with diabetes--76.5% males, aged 61.5 +/- 8.5 years with a mean glycated haemoglobin of 9.2 +/- 2.2% presenting for care at a large, multidisciplinary wound care centre. All patients received surgical debridement for their diabetic foot wounds and were placed on therapy consisting of a single application of an acellular matrix graft (GraftJacket; Wright Medical Technologies, Arlington, TN, USA) with dressing changes taking place weekly. Outcomes evaluated included time to complete wound closure and proportion of patients achieving wound closure in 20 weeks. Acellular matrix therapy was used as initial therapy and was sutured or stapled in place under a silicone-based non adherent dressing. Therapy was then followed by a moisture-retentive dressing until complete epithelialisation. In total, 82.4% of wounds measuring a mean 4.6 +/- 3.2 cm(2) healed in the 20-week evaluation period. For those that healed in this period, healing took place in a mean 8.9 +/- 2.7 weeks. We conclude that a regimen consisting of moist wound healing using an acellular matrix dressing may be a useful adjunct to appropriate diabetic foot ulcer care for deep, non-infected, non-ischaemic wounds. We await the completion of further trials in this area to confirm or refute this initial assessment.     

Management of wounds in the diabetic foot

Current management of wounds in the diabetic foot is detailed. A thorough initial clinical examination and non-invasive tests can give baseline values and provide valuable information about limb and foot circulation. The approach detailed involves limited amputation and preservation of as much of the weight-bearing surface as possible.     

Use of injectable collagen to treat chronic diabetic foot ulcers

A significant portion of the population suffer from diabetic foot ulcers. While conservative treatment is often successful, many diabetic patients with accompanying peripheral vascular disease and neuropathy are under constant medical care for chronic, recurring foot ulcers. A new injectable biomaterial, Keragen Implant, was evaluated on two patients with bilateral diabetic ulcers. The implanted lesions healed completely during the months following treatment. Control lesions treated by conventional means remained open and ulcerated.     

Role of diabetic microvascular disease in the development of foot wounds

The influence of microvascular changes in diabetic foot tissue breakdown is not fully known. Research on the role of vascular mediators in diabetes and their effect on the microvasculature may help to create a more unified theory.     

Measurement of optical properties to quantify healing of chronic diabetic wounds

Measurement of scattering and absorption characteristics of tissue by near infrared spectroscopy may provide a clinically applicable, quantitative method of assessing healing of diabetic wounds. Twenty SICH-1 hairless rats were divided into a control group and a streptozotocin-induced diabetic group. Full-thickness wounds were made on the dorsal surface of each animal. Wounds were examined using a near infrared device with three wavelengths of incident light. Amplitude and phase of scattered light were obtained at four different source detector distances at each wavelength. The probe was positioned at six different locations. Tissue absorption and scattering coefficients were calculated from amplitude and phase data. Wound dimensions were calculated by cross and parallel polarization. Thirty-eight wounds were evaluated during the experiment. Wound size decreased at twice the rate in the control animals, whereas the average absorption coefficient was higher by a factor of two while the average value of the reduced scattering coefficient was 30% higher in the diabetic wounds. During healing, both scattering and absorption coefficients increased faster in the diabetics. Higher absorption in diabetic rats suggests impaired blood flow. Scattering may reflect tissue disorganization observed in delayed wound healing. We conclude that near infrared spectroscopy may differentiate between healing diabetic and nondiabetic wounds.     

Neurogenic factors in the impaired healing of diabetic foot ulcers

BACKGROUND: We hypothesize that the reduced innervation of skin can be observed both in clinically neuropathic and non-neuropathic diabetic foot ulcers and can contribute to low inflammatory cell infiltration. MATERIALS AND METHODS: Twenty patients with type 2 diabetes and active foot ulcers, without clinical evidence of peripheral sensory neuropathy (n = 12) and with sensory neuropathy (n = 8) were involved in this study. Biopsies from ulcer margin were examined immunohistochemically. RESULTS: Studies revealed presence of protein gene product 9.5 (PGP9.5)+ nerve endings only in reticular dermis in 3 of 12 non-neuropathic subjects, however, regenerating GAP-43+ endings were seen in dermis of almost all specimens. Lack of substance P+ nerve endings was characteristic for both groups. The reduced distribution of calcitonin gene-related peptide+ nerves in epidermis and dermis was seen mainly in neuropathic group. In neo-epidermis lack of nerve growth factor expression was observed in both groups, whereas neurotrophin 3 immunostaining was characteristic for neuropathic specimens (P < 0.03). Expression of trkA and trkC receptors did not differ significantly between groups. Low inflammatory cell infiltration and moderate presence of fibroblasts was characteristic for all studied specimens. CONCLUSIONS: The observed reduction of foot skin innervation and neurogenic factors expression can be correlated with low inflammatory cell accumulation and subsequently leads to the observed chronicity of diabetic foot ulcer healing process in both neuropathic and non-neuropathic patients.     

Synthesis of type I collagen in healing wounds in humans.

To quantify wound healing in surgical patients, samples of wound fluid were collected through a silicone rubber tube for 7 postoperative days and their concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured with specific radioimmunoassays. The mean concentration of PICP in would fluid on day 1 was 207 +/- 92 (SD) micrograms/L, and on day 2 908 +/- 469 micrograms/L (p less than 0.001, signed rank test). On day 7, the mean concentration reached was 380 times higher than that of day 1 (79,330 +/- 54,151 micrograms/L). Only one peak of PICP antigenicity, corresponding to the intact propeptide as set free during synthesis of type I procollagen, was detected on Sephacryl S-300 gel filtration analysis of wound fluid samples. The mean concentration of PIIINP was 70 +/- 61 micrograms/L on day 1, 86 +/- 88 micrograms/L on day 2, and 180 +/- 129 micrograms/L on day 3 (p less than 0.001 when compared with day 1). Finally on day 7, a 250-fold concentration (17,812 +/- 9839 micrograms/L), compared with day 1, was reached. Methods described in the present paper allow separate and repetitive quantification of the synthesis of both type I and type III procollagen during human wound healing.     

Exploring the use of an alginate dressing for diabetic foot ulcers

Few studies have investigated the use of dressings on patients with diabetic foot ulceration. This paper reports the results of a non-comparative, two-centre study investigating the performance characteristics of SeaSorb dressing in patients with this condition. This was an exploratory study to determine the potential use of this dressing, and not a large randomised control trial. All patients had diabetic foot ulceration of 1 cm or more in diameter, classified as Wagner grade I or II, with an ankle brachial pressure index of > 0.4. The investigators carried out objective assessments including photography and ulcer tracing as well as subjective assessments of exudate levels, wound bed condition, peri-ulcer skin condition, ease of application and removal of the dressing, dressing conformability, discomfort during dressing application and removal, and clinical signs of infection. Investigators recruited 41 patients in two sites (31 in site one and 10 in site two). Of these, the findings relating to 39 patients could be evaluated. The patients were treated for a maximum of six weeks or until the ulcer healed. The study found that 28.2% (11/39) of the ulcers healed within the six-week period. Overall, there was a significant reduction in mean ulcer area from 2.8 cm 2 to 1.02 cm 2 from week 0 to week six. The relative ulcer area showed a significant decrease from 100% to 33%. For patients who experienced ulcer pain (11 patients), its intensity decreased over the six weeks. Severe maceration was not reported for any patient throughout the study. Six patients required treatment for infection. A total of 12 adverse events were reported: seven mild to moderate and five severe. None were directly attributed to the study dressing.     

Puncture wounds in the diabetic foot: importance of X-ray in diagnosis

It is well recognised that septic sequelae of puncture wounds are worse in diabetics. Since much of the spreading foot sepsis from puncture wounds is deep to the deep fascia, and because the sole of the foot has thick skin and subcutaneous fibrous septae, crepitus is not as easily appreciated as it is at other sites. Also the rubor of the inflammatory response is minimal in subfascial sepsis and it is therefore easy to underestimate the extent of deep gangrene. The absence of pain due to neuropathy also masks the inflammatory reaction and makes a foreign body or severe osteomyelitis less obvious clinically. These cases demonstrate the value of routine and early radiographs in the assessment of puncture wounds in diabetic feet.     

Use of hyperspectral imaging to predict healing of diabetic foot ulceration

Our main objective was to validate that hyperspectral imaging via a new portable camera carries the potential to provide a reliable clinical biomarker that can predict DFU healing. We recruited patients with diabetic foot ulceration (DFU) without peripheral arterial disease, infection or other serious illness. Using an hyperspectral imaging (HSI) apparatus, post-debridement hyperspectral images were taken evaluating the ulcer size, periwound oxyhemoglobin (OxyHb), deoxyhemoglobin level (DeoxyHb) and oxygen saturation (O₂Sat) for four consecutive visits. Twenty-seven patients were followed, out of whom seven healed their DFU while the remaining 20 failed to heal their DFU. The average time between each visit was 3 weeks. Binary logistic regression of healers versus non-healers on Visit 1 oxyHb and on Visit 2 showed a significant inverse association, OR = 0.85 (95% CI: 0.73–0.98, p < 0.001). An inverse correlation was observed between the Visit 1 oxyHb and the percentage of ulcer size reduction between Visit 1 and Visit 4 (r = −0.46, p = 0.02) and between the Visit 2 oxyHb and the percentage of ulcer size reduction between Visits 2 and 4 (r = −0.65, p = 0.001). Using oxyHb 50 as the cut-off point to predict DFU complete healing, Visit 1 oxyHb measurement provided 85% sensitivity, 70% specificity, 50% positive predictive value and 93% negative predictive value. For Visit 2, oxyHb had 85% sensitivity, 85% specificity, 66% positive predictive value and 94% negative predictive value. We conclude that this preliminary study, which involved a relatively small number of patients, indicates that hyperspectral imaging is a simple exam that can easily be added to daily clinical practice and has the potential to provide useful information regarding the healing potential of DFU over a short period of time.     

外源性透明质酸对创面愈合组织的影响

目的：研究外源性透明质酸对创面愈合组织中生化组分的影响，以期探索外源性HA在创伤愈合中的作用及其机制。方法：在小型猪背部的去中厚皮创面上应用不同浓度和剂型的外源性HA，并于术后第3、7、14、21、28天切取创面组织及正常皮肤，测定其糖胺多糖、HA及Ⅲ型胶原的含量变化。结果：愈合过程中，实验组创面愈合组织中的GAG、HA含量逐渐升高，1周时达峰值并能维持3周；创面对照组术后3天也见增高，但随后即迅速下降。实验组的Ⅲ型胶原含量也始终明显高于对照组，其中又以1．0％、2．0％HA组最高。结论：外源性HA能显著增高愈合组织中HA、Ⅲ型胶原含量并能维持较长时间，从而有利于创伤愈合及减轻瘢痕形成。     

Evidence of differential microbiomes in healing versus non‐healing diabetic foot ulcers prior to and following foot salvage therapy

Diabetic foot ulcers (DFU) contribute to 80% of lower extremity amputations. Although physicians currently rely on clinical signs along with non‐specific biomarkers of infection, such as erythrocyte sedimentation rate and C‐reactive protein, to diagnose and monitor DFU, there is no specific and sensitive measure available to monitor or prognosticate the success of foot salvage therapy (FST). To address this we performed a prospective, observational microbiome analysis to test the hypotheses that: (i) the initial microbiomes of healed versus non‐healed DFU are distinct; (ii) the microbial load, diversity and presence of pathogenic organism of the DFU change in response to antibiotics treatment; and (iii) the changes in the DFU microbiome during treatment are prognostic of clinical outcome. To test this, microbiome analyses were performed on 23 DFU patients undergoing FST, in which wound samples were collected at zero, four, and eight weeks following wound debridement and antibiotics treatment. Bacterial abundance was determined using quantitative polymerase chain reaction (qPCR). Eleven patients healed their DFU, while FDT failed to heal DFU in the other 12 patients. Microbiome results demonstrated that healing DFUs had a larger abundance Actinomycetales and Staphylococcaceae (p < 0.05), while DFUs that did not heal had a higher abundance of Bacteroidales and Streptococcaceae (p < 0.05). FST marked increases Actinomycetales in DFU, and this increase is significantly greater in patients that healed (p < 0.05). Future studies to confirm the differential microbiomes, and that increasing Actinomycetales is prognostic of successful FST are warranted. Statement of Clinical Significance: Tracking changes in the prevalence of pathogens in diabetic foot ulcers may be a clinical tool for monitoring treatment response to foot salvage therapy and prognosticating the need for further surgical intervention. The initial wound sample microbiome may provide important prognostic information on the eventual clinical outcome of foot salvage therapy. It may serve as an important clinical tool for patient counseling and making surgical decision of pursuing foot salvage versus amputation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1596–1603, 2019.     

Early healing events in a porcine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis, and healing

A porcine model of wound healing was employed to examine the impact of nanocrystalline silver-coated dressings on specific wound healing events. Full-thickness wounds were created on the backs of pigs, contaminated with an experimental inoculum containing Pseudomonas aeruginosa, Fusobacterium sp., and coagulase-negative staphylococci, and covered with dressing products either containing silver or not. Nanocrystalline silver-coated dressings promoted rapid wound healing, particularly during the first several days post-injury. Healing was characterized by rapid development of well vascularized granulation tissue that supported tissue grafting 4 days post-injury, unlike control dressed wounds. The proteolytic environment of wounds treated with nanocrystalline silver was characterized by reduced levels of matrix metalloproteinases. Matrix metalloproteinases have been shown to be present in chronic ulcers at abnormally high levels, as compared with acute wounds, and may contribute to the nonhealing nature of these wounds. Cellular apoptosis occurred at a higher frequency in the nanocrystalline silver-treated wounds than in wounds dressed with other products. The results suggest that nanocrystalline silver may play a role in altering or compressing the inflammatory events in wounds and facilitating the early phases of wound healing. These benefits are associated with reduced local matrix metalloproteinase levels and enhanced cellular apoptosis.     

The use of marrow-derived stem cells to accelerate healing in chronic wounds

Adult bone marrow-derived stem cells may aid the healing of chronic lower extremity wounds by transplanting a population of progenitor cells locally into the wound. We present results from three cases in which bone marrow aspirate containing marrow-derived cells was applied/injected locally into complex lower extremity chronic wounds of differing aetiologies. Our case series suggest that bone marrow aspirate, applied topically and injected into the wound periphery, may be a useful and potentially safe adjunct to wound simplification and ultimate closure.     

An observational pilot study using a purified reconstituted bilayer matrix to treat non‐healing diabetic foot ulcers

Diabetic foot ulcers (DFUs) have significant clinical impact and carry a substantial economic burden. Patients with DFUs that are refractory to standard wound care are at risk for major complications, including infection and amputation and have an increased risk of mortality. This study evaluated the safety and preliminary efficacy of a novel decellularised purified reconstituted bilayer matrix (PRBM) in treating DFUs. Ten diabetic patients with refractory wounds that failed to heal after at least 4 weeks of standard wound care were studied in this Institutional Review Board approved trial. Ten consecutive wounds were treated weekly with the PRBM for up to 12 weeks. At each weekly visit, the wound was evaluated, photographed, and cleaned, followed by application of new graft if not completely epithelialised. Assessment included measurement of the wound area and inspection of the wound site for signs of complications. The primary outcome measure was wound closure, as adjudicated by independent reviewers. Secondary outcomes included assessment of overall adverse events, time to closure, percent area reduction, and the cost of product(s) used. Nine of 10 patients achieved complete wound closure within 4 weeks, and 1 did not heal completely within 12 weeks. The mean time to heal was 2.7 weeks. The mean wound area reduction at 12 weeks was 99%. No adverse events nor wound complications were observed. These early clinical findings suggest that the PRBM may be an effective tool in the treatment of diabetic foot ulcers.     

Bi-layered living cellular construct resulted in greater healing in an alloxan-induced diabetic porcine model

Tissue-engineered skin constructs, including bi-layered living cellular constructs (BLCC) used in the treatment of chronic wounds, are structurally/functionally complex. While some work has been performed to understand their mechanisms, the totality of how BLCC may function in wound healing remains unknown. To this end, we have developed a delayed wound healing model to test BLCC cellular and molecular mechanisms of action. Diabetes was chemically-induced using alloxan in Yucatan miniature pigs, and full-thickness wounds were generated on their dorsum. These wounds were either allowed to heal by secondary intention alone (control) or treated with a single or multiple treatments of a porcine autologous BLCC. Results indicated a single treatment with porcine BLCC resulted in statistically significant wound healing at day 17, while four treatments resulted in statistically significant healing on days 10, 13, and 17 compared to control. Statistically accelerated wound closure was driven by re-epithelialisation rather than contraction or granulation. This porcine diabetic model and the use of a porcine BLCC allowed evaluation of healing responses in vivo without the complications typically seen with either xenogenic responses of human/animal systems or the use of immune compromised animals, expanding the knowledge base around how BLCC may impact chronic wounds.     

湿性愈合理论在糖尿病足伤口处理中的实践

目的探讨处理糖尿病足伤口的方法。方法对2004年3月～2010年6月运用先进的湿性愈合敷料处理的糖尿病足伤口61例进行回顾性分析。结果湿性愈合敷料能溶解伤口坏死组织,有助于自溶性清创、促进肉芽生长。结论湿性愈合理论指导下的糖尿病足伤口处理方法能达到加快伤口愈合、有效降低致残率,提高病人的生存质量的目的。