Postinflammatory Hyperpigmentation Following Mohs Micrographic Surgery: An Observational Study.

IMPORTANCE: Functional and cosmetic outcomes following Mohs micrographic surgery (MMS) are poorly studied in individuals with skin of color (SOC). Postinflammatory hyperpigmentation (PIH) may be long-lasting and highly distressing. SOC individuals are particularly susceptible to PIH following procedures.  Objective: To characterize factors that contribute to the development of PIH following MMS in SOC. DESIGN: This retrospective study included 72 SOC individuals with 83 cases of keratinocyte carcinoma treated with MMS between August 2020 and August 2021 at a single medical center in the Bronx, New York. RESULTS: Postinflammatory hyperpigmentation following Mohs micrographic surgery was more common in Fitzpatrick skin types (FST) IV to V (48.0%) compared to FST I to III (18.2%; P=0.006). Grafts and granulation resulted in higher rates of PIH compared to linear repairs and flaps (87.5% vs 30.7%; P=0.003). Cases with postoperative complications resulted in higher rates of PIH compared to cases without (81.8% vs 29.2%; P=0.001). In a subset analysis of linear repairs, polyglactin 910 as a subcutaneous suture produced a higher rate of PIH compared to poliglecaprone 25 (46.2% vs 7.1%; P=0.015).  Conclusions and Relevance: Individuals with SOC (FST IV to V) are more likely to develop PIH following MMS. Grafts and granulation lead to PIH more often than linear repairs and flaps. Postoperative complications significantly increase the risk of PIH. Surgeons should consider these risk factors during surgical planning in an effort to mitigate PIH in SOC individuals. Studies with larger sample sizes are indicated.  J Drugs Dermatol. 2024;23(5):316-321. doi:10.36849/JDD.8146.

Role of the mitochondrial protein cyclophilin D in skin wound healing and collagen secretion.

Central for wound healing is the formation of granulation tissue, which largely consists of collagen and whose importance stretches past wound healing, including being implicated in both fibrosis and skin aging. Cyclophilin D (CyD) is a mitochondrial protein that regulates the permeability transition pore, known for its role in apoptosis and ischemia-reperfusion. To date, the role of CyD in human wound healing and collagen generation has been largely unexplored. Here, we show that CyD was upregulated in normal wounds and venous ulcers, likely adaptive as CyD inhibition impaired reepithelialization, granulation tissue formation, and wound closure in both human and pig models. Overexpression of CyD increased keratinocyte migration and fibroblast proliferation, while its inhibition reduced migration. Independent of wound healing, CyD inhibition in fibroblasts reduced collagen secretion and caused endoplasmic reticulum collagen accumulation, while its overexpression increased collagen secretion. This was confirmed in a Ppif-KO mouse model, which showed a reduction in skin collagen. Overall, this study revealed previously unreported roles of CyD in skin, with implications for wound healing and beyond.

"Simmer pus and grow flesh" method promotes chronic wound healing in rats via bFGF-Wnt ß-catenin signaling pathway.

The purpose of this study was to explore the mechanism of "simmer pus and grow meat" method based on bFGF regulating WNT / ß-Catenin signaling pathway. Of 100 SPF rats, 25 were randomly selected as blank group, and 75 rats were established chronic infectious wound model and divided into blank group, model group (normal saline treatment, n = 25), experimental group (purple and white ointment treatment, n = 25), and wet burn ointment group (wet burn treatment, n = 25). The wound healing rate of rats was compared. The protein expressions of PCAN, VEGF, bFGF, ß-Catenin, GSK-3ß and C-Myc in granulation tissues were detected. On the 7th day, the wound healing rate of the model group was lower than that of the other 3 groups (P<0.05), and the wound healing rate of the positive control group was higher than that of the experimental group and the control group (P<0.05). The expressions of bFGF, GSK-3ß and C-MyC in model group were higher than those in control group (P<0.05). The ß-catenin protein expression in the model group was lower than that in the control group (P<0.05), and the ß-catenin protein expression in the experimental group and the positive control group was higher than that in the model group (P<0.05). The expressions of PCAN and VEGF in model group were lower than those in model group (P<0.05). We found that Zibai ointment promotes chronic wound healing by modulating the bFGF/Wnt/ß-Catenin signaling pathway.

Correlation between inflammatory factors, autophagy protein levels, and infection in granulation tissue of diabetic foot ulcer.

OBJECTIVE: To observe the expression of inflammatory factors and autophagy-related proteins in granulation tissue of diabetic foot ulcer (DFU) patients and analyze their relationship with infection. METHODS: This is a retrospective cohort study. One hundred and fifty-two patients with DFU in our hospital from July 2020 to March 2022 were selected as the DFU group, including 98 cases in infection stage group and 54 cases in infection control group. The patients were further graded as the mild (51 cases), the moderate (65 cases), and the severe infection group (36 cases) according to the Wagner grading criteria. Sixty-seven patients with foot burns during the same period were selected as the control group. The distribution of pathogenic bacteria on the ulcer surface was examined using fully automated bacterial analyzer. The expression of inflammatory factors (procalcitonin [PCT], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) was valued by real-time fluorescence quantitative PCR (qRT-PCR). Protein expression was measured by immunohistochemistry (IHC). The correlation was analyzed by Pearson. RESULTS: The surface infection of DFU patients was mostly induced by gram-negative and gram-positive bacteria, with Pseudomonas aeruginosa predominating among the Gram-negative bacteria and Staphylococcus aureus among the gram-positive bacteria. The infection stage group had higher content of PCT, TNF-α, and IL-6 and lower content of Beclin-1 and LC3 than the infection control group (p < .001). The levels of PCT, TNF-α, and IL-6 in the DFU patients with cardiovascular events were higher than those in the nonoccurrence group (p < .001). Glycated hemoglobin in patients with DFU was positively correlated with PCT, TNF-α, and IL-6 levels (p < .05), and negatively correlated with Beclin-1 and LC3 levels (p < .001). CONCLUSION: P. aeruginosa and S. aureus were predominant bacterial in DFU infections. Inflammatory factor and autophagy protein expression were closely correlated with the degree of infection.

Experience of diagnosis and treatment of hard-to-heal wounds infected with Acinetobacter baumannii: a case study.

OBJECTIVE: To explore the efficacy of 0.01% hypochlorous acid (HOCl) in the treatment of hard-to-heal wounds infected by multidrug-resistant Acinetobacter baumannii. METHOD: We report a case of hard-to-heal wounds on a patient's forearms that were infected by Acinetobacter baumannii. The wounds were treated with 0.01% HOCl. We reviewed the relevant literature and discussed the definition, epidemiology and pathogenesis of hard-to-heal wounds infected by Acinetobacter baumannii. We also explored the safety and efficacy of 0.01% HOCl for the treatment of hard-to-heal wounds infected with Acinetobacter baumannii. RESULTS: After 3-4 weeks of treatment with 0.01% HOCl, the pain and pruritus of the wounds was gradually alleviated, the infection was controlled and the granulation tissue was fresh. The ulcers also shrank and the nutritional condition of the patient improved. In the fifth week, the skin of the patient's right thigh was grafted to repair the wounds, which then healed within 18 days. During the three years of follow-up, the patient had no relapse. CONCLUSION: In our case, the 0.01% HOCl seemed to effectively inactivate the bacterial biological biofilm. This helped to promote wound healing, and was non-toxic to the tissues. We consider low-concentration HOCl to be safe and effective for the treatment of hard-to-heal wounds infected with Acinetobacter baumannii.

Immunologic burden links periodontitis to acute coronary syndrome: levels of CD4 + and CD8 + T cells in gingival granulation tissue.

OBJECTIVE: To investigate the proportional variation of macrophage and T-lymphocytes subpopulations in acute coronary syndrome (ACS) patients, its association with periodontitis (P), and to compare with control individuals. SUBJECTS AND METHODS: Three groups of subjects participated: one group consisted of 17 ACS patients with P (ACS + P), another group consisted of 22 no ACS + P patients, and a control group consisted of 23 participants with gingivitis (no ACS + G). Macrophage, CD4 + , and CD8 + T-lymphocytes and CD4 + /CD8 + ratio values in gingival tissue were determined histometrically. RESULTS: Significant differences were found among three groups regarding the mean number of macrophage (no ACS + P > ACS + P > no ACS + G; p < 0.05) and CD8 + T-lymphocytes (no ACS + P > ACS + P > no ACS + G; p < 0.05). Significant variations were observed between the groups both CD4 + T-lymphocytes densities (ACS + P > no ACS + P and ACS + P > no ACS + G; p < 0.05) and CD4 + / CD8 + ratio (no ACS + P < no ACS + G and ACS + P < no ACS + G; p < 0.05). CONCLUSIONS: The increased number of CD8 + T-lymphocytes in both group ACS + P and group no ACS + P resulted in a reduction of the CD4 + /CD8 + ratio in gingival tissue when compared with no ACS + G group. CLINICAL RELEVANCE: The decrease of CD4 + /CD8 + ratio in gingival tissue reflects periodontitis and may be associated with severe adverse outcomes in people with ACS.

Airway necrosis and granulation tissue formation caused by Rhizopus oryzae leading to severe upper airway obstruction: a case report.

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host's immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.

Perifascial areolar tissue graft promotes angiogenesis and wound healing in an exposed ischemic component rabbit model.

Multiple studies have reported the use of perifascial areolar tissue (PAT) grafts to treat wounds involving exposed ischemic tissues, avascular structures, and defective membrane structures. Our objective was to assess the quantitative effects of PAT grafts and their suitability for wounds with ischemic tissue exposure and to qualitatively determine the factors through which PAT promotes wound healing and repair. We conducted histological, immunohistochemical, and mass spectrometric analyses of the PAT grafts. PAT grafts contain numerous CD34+ progenitor/stem cells, extracellular matrix, growth factors, and cytokines that promote wound healing and angiogenesis. Furthermore, we established a male rabbit model to compare the efficacy of PAT grafting with that of an occlusive dressing treatment (control) for wounds with cartilage exposure. PAT grafts could cover ischemic components with granulation tissue and promote angiogenesis. Macroscopic and histological observations of the PAT graft on postoperative day seven revealed capillaries bridging the ischemic tissue (vascular bridging). Additionally, the PAT graft suppressed wound contraction and alpha smooth muscle actin (αSMA) levels and promoted epithelialization. These findings suggested that PAT can serve as a platform to enhance wound healing and promote angiogenesis. This is the first study to quantify the therapeutic efficacy of PAT grafts, revealing their high value for the treatment of wounds involving exposed ischemic structures. The effectiveness of PAT grafts can be attributed to two primary factors: vascular bridging and the provision of three essential elements (progenitor/stem cells, extracellular matrix molecules, and growth factors/cytokines). Moreover, PAT grafts may be used as transplant materials to mitigate excessive wound contraction and the development of hypertrophic scarring.

Bioactive-Glass-Based Materials with Possible Application in Diabetic Wound Healing: A Systematic Review.

Diabetes affected 537 million adults in 2021, costing a total of USD 966 billion dollars in healthcare. One of the most common complications associated with diabetes corresponds to the development of diabetic foot ulcers (DFUs). DFUs affect around 15% of diabetic patients; these ulcers have impaired healing due to neuropathy, arterial disease, infection, and aberrant extracellular matrix (ECM) degradation, among other factors. The bioactive-glass-based materials discussed in this systematic review show promising results in accelerating diabetic wound healing. It can be concluded that the addition of BG is extremely valuable with regard to the wound healing rate and wound healing quality, since BG activates fibroblasts, enhances M1-to-M2 phenotype switching, induces angiogenesis, and initiates the formation of granulation tissue and re-epithelization of the wound. In addition, a higher density and deposition and better organization of collagen type III are seen. This systematic review was made using the PRISMA guideline and intends to contribute to the advancement of diabetic wound healing therapeutic strategies development by providing an overview of the materials currently being developed and their effect in diabetic wound healing in vitro and in vivo.

Utilization of Topical Polysporin and Triamcinolone for the Treatment of Hypergranulation Tissue.

Hypergranulation is the abnormal accumulation of granulation tissue in a wound and is commonly seen in burns. It impairs wound healing and can predispose patients to infection. There is no gold standard treatment for hypergranulation tissue, but some options include surgical debridement, chemical cautery with silver nitrate, and topical steroids. Silver nitrate treatment is painful and can lead to scarring, so topical steroid use is on the rise. A retrospective review, between January 1, 2017 and August 30, 2021, at a tertiary burn center was performed to analyze outcomes of hypergranulation tissue after treatment with a topical 50/50 mixture of triamcinolone (Perrigo, Dublin, Ireland) and Polysporin (Johnson & Johnson, New Brunswick, NJ). One hundred and sixteen patients were treated with triamcinolone and Polysporin for hypergranulation tissue, although 24 did not meet inclusion criteria. Eighty-eight out of 92 patients were successfully treated until hypergranulation resolution, while 4/92(4.3%) required silver nitrate or surgery despite the topical cream to achieve resolution. In the 88 patients successfully treated until hypergranulation resolution, 99 areas of hypergranulation were treated. Forty-one of 99 (41.4%) hypergranulation areas resolved within 2 weeks. The average time to hypergranulation resolution was 27.5 ± 2.5 days. We found that a novel 50/50 mixture of triamcinolone and Polysporin topical ointment is an effective and safe treatment for hypergranulation tissue in burn wounds. Further prospective studies are needed to determine its efficacy and safety profile.

Efficacy of one-hour negative pressure wound therapy and magnetic field energy in wound healing.

OBJECTIVE: Wound healing is an important aspect of health but needs further research to identify the effects and interactions of different treatment approaches on healing. The aims of this study were to investigate the effectiveness of one-hour negative pressure wound therapy (NPWT) and compare histological differences between one-hour NPWT and magnetic field energy (MFE) in rats on early-stage wound healing, wound size and angiogenesis. METHOD: Standardised wounds were created on Wistar rats that were allocated and divided into NPWT, MFE and control groups. Both treatments were applied for 1 hour/day for 10 days. Wound size, histological changes and wound area blood flow were assessed. RESULTS: The wound size of all groups was similar on days 0, 2 and 10. The MFE group's wound size was smaller than the NPWT group on days 4, 6 and 8 (p<0.05). Development of the granulation tissue in both the one-hour NPWT and MFE groups was greater than in the control group. Additionally, the inflammatory phase was shorter, and wounds entered the proliferative stage faster in the MFE group than both of the other groups. CONCLUSION: Treatment with MFE may be more effective in terms of early stage wound closure and angiogenesis. On the other hand, the NPWT group's wound area blood flow was significantly greater than the other two groups. MFE is superior to one-hour NPWT in terms of wound area and angiogenesis. Furthermore, it is worthwhile to note that one-hour NPWT increases bloodflow in the wound area, which stimulates healing.

Nanofat Accelerates and Improves the Vascularization, Lymphatic Drainage and Healing of Full-Thickness Murine Skin Wounds.

The treatment of wounds using the body's own resources is a promising approach to support the physiological regenerative process. To advance this concept, we evaluated the effect of nanofat (NF) on wound healing. For this purpose, full-thickness skin defects were created in dorsal skinfold chambers of wild-type mice. These defects were filled with NF generated from the inguinal subcutaneous adipose tissue of green fluorescent protein (GFP)+ donor mice, which was stabilized using platelet-rich plasma (PRP). Empty wounds and wounds solely filled with PRP served as controls. Wound closure, vascularization and formation of granulation tissue were repeatedly analyzed using stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. PRP + NF-treated wounds exhibited accelerated vascularization and wound closure when compared to controls. This was primarily due to the fact that the grafted NF contained a substantial fraction of viable GFP+ vascular and lymph vessel fragments, which interconnected with the GFP- vessels of the host tissue. Moreover, the switch from inflammatory M1- to regenerative M2-polarized macrophages was promoted in PRP + NF-treated wounds. These findings indicate that NF markedly accelerates and improves the wound healing process and, thus, represents a promising autologous product for future wound management.

External peri-stomal skin granulations in paediatric tracheostomy: Incidence, outcomes and a proposed treatment algorithm.

BACKGROUND: External peri-stomal skin granulations after tracheostomy in children are common and may interfere with routine tube changes. This study is the first attempt to describe the incidence and outcomes, along with a proposed treatment algorithm. METHODS: A retrospective review of all inpatient children with a tracheostomy between January 2020 and May 2022 at the Royal Hospital for Children (RHC) in Glasgow. The presence of external peri-stomal granulation, date of onset and resolution, recurrence and treatment modalities were noted. All tracheostomy tubes used during the study period were made of silicone. RESULTS: A total of 50 episodes of peri-stomal granulation were identified in 27 children (52 %). Median age at the end of the study period was 4.3 years, with younger children experiencing more frequent granulation. 3 episodes interfered with tracheostomy tube changes. Time to resolution of the granulation was significantly longer with topical steroid/antimicrobial ointment monotherapy, but recurrence was less common when this was used a first treatment modality. CONCLUSION: Non-invasive measures such as topical anti-microbials should be used in the first instance when managing external stoma-site granulations. More invasive measures, such as silver nitrate cautery and surgical excision, should be considered if the granulation tissue is not improving or when it poses a risk to safe tube changes.

Prevalence of Chlamydia infection detected by immunohistochemistry in patients with anorectal ulcer and granulation tissue.

Anorectal ulcer with granulation tissue is typically associated with left-sided inflammatory bowel disease or infection. Due to emerging cases of Chlamydia proctitis, we aim to investigate the prevalence of Chlamydia infection using immunohistochemistry (IHC) in anorectal biopsies showing ulcer and granulation tissue. Seventy-seven patients including 60 males and 17 females with mean age of 51 years old were retrospectively identified in surgical pathology archives. Chlamydia IHC was validated with a monoclonal antibody on an index who was positive for Chlamydia by rectal swab nucleic acid amplification test (NAAT), then performed on formalin fixed and paraffin embedded (FFPE) tissue sections. Confirmative molecular test using real-time PCR was performed on DNA extractions of 14 IHC-positive and 14 IHC-negative FFPEs, 18 NAAT-positive, and 5 NAAT-negative cytology specimens. Chlamydia IHC showed strong intracytoplasmic or extracellular sphere morphology in 14 of 77 (18.2 %) FFPEs, including 11 of 60 (18.3 %) males and 3 of 17 (17.6 %) females (age 11-84 years). Eight of 14 (57.1 %) Chlamydia-IHC positive patients had known history of STDs, high-risk behavior, or immunosuppressive conditions. One of 14 (7.1 %) IHC-positive FFEP and 15 of 18 (83.3 %) NAAT-positive cytology cases were confirmed by real-time PCR. Chlamydia inclusions were detected in all 4 randomly selected NAAT and PCR-positive cytology specimens by IHC. Our data suggested that Chlamydia infection is more prevalent than we thought in patients with active proctitis and ulceration. Chlamydia IHC may be performed as a screening test in biopsies to facilitate early detection of this treatable proctitis in high-risk population.

Temporal Bone Osteomyelitis Masquerading as Malignancy: A Diagnostic Challenge.

Xanthogranulomatous osteomyelitis is a rare chronic inflammatory disorder. Until now, it has only been reported in long bones. To the best of our knowledge, it has never been reported in temporal bone. We present the case of this rare disease in a 64-year-old male involving the temporal bone, presenting with ear pain, discharge, decreased hearing, and granulation tissue in the external auditory canal, mimicking malignancy clinically and radiologically. The patient was unresponsive to medical management and was taken up for surgical debridement, followed by treatment with systemic and topical antibiotics, with a successful outcome. As this disease has not been reported in the literature yet in the temporal bone and mimics malignancy, it must be differentiated on histopathology to establish a definite diagnosis and provide appropriate management. A long-term follow-up is also necessary to recognize the clinical behavior of this disease, as no treatment protocol has been established yet.

Policresulen to treat hypergranulation tissue around drainage tubes.

OBJECTIVE: To evaluate the efficacy of policresulen for the treatment of hypergranulation. METHOD: This was a retrospective study of patients with percutaneous catheters. Inpatients from two hospitals and those from outpatient clinics were included. Approximately 2ml of 50% policresulen solution was applied to hypergranulation tissue, which was then immediately pressed with gauze for 1-3 minutes using light pressure. When haemostasis was achieved and the granulation tissue size decreased, the procedure was terminated. RESULTS: A total of eight patients (four females and four males) were included in this study. Effective haemostasis was achieved in all patients. The size of the hypergranulation tissue decreased with policresulen treatment, and resolved completely in one patient. There were no complications. Hypergranulation tissue recurred in one patient. Haemostasis was successfully achieved after repeated procedures. CONCLUSION: The findings of this study showed policresulen to be an inexpensive, easy treatment for hypergranulation at catheter insertion sites.

Efficacy of wearable vibration dressings on full-thickness wound healing in a hyperglycemic rat model.

Local low-frequency vibration promotes blood flow and wound healing in hard-to-heal diabetic foot ulcers (DFUs). However, vibration treatment is challenging in patients with DFUs due to wound management difficulties and low adherence. Consequently, developing wearable self-care devices becomes imperative for effective wound healing. This study introduces a wearable vibration dressing and assesses its impact on wound healing in hyperglycemic rats. Low-frequency vibration at 52 Hz was applied to the wound for 40 min/day in awake rats. Relative wound areas on post-wounding days (PWDs) 4-7 were significantly smaller and the wound closure rate was significantly higher in the vibration group than in the control group (p < 0.05, respectively). The total haemoglobin at baseline and after vibration on post-wounding day 7 was significantly larger in the vibration group than in the control group (p < 0.05). On PWD 7, the thickness of the granulation tissue was significantly higher in the vibration group than in the control group (p < 0.05). Moreover, the number of blood vessels at the wound site and vascular endothelial growth factor A protein expression were significantly higher in the vibration group than in the control group (p < 0.05, respectively). The ratio of (CD68+ /iNOS+ )/(CD163+ ) macrophages in the vibration group was significantly lower than that in the control group (p < 0.05). These results indicate the potential of wearable vibration dressings as new self-care devices that can promote angiogenesis and blood flow, improve inflammation, and enhance wound healing in DFUs.

Immunohistochemical study of CD31 and α-SMA expression for age estimation of porcine skin wounds.

Age estimation of wounds in veterinary forensic investigations is based on the presence and amount of granulation tissue. However, accurate age assessment is challenging and new time-dependent markers are warranted to support and improve the current procedure. The objective of this study was to evaluate the expression of CD31-positive blood vessels and α-smooth muscle action (α-SMA)-positive myofibroblasts in granulation tissue in order to evaluate their value as markers for porcine wound age estimation in a veterinary forensic context. Immunohistochemical expression of CD31 and α-SMA in 14 experimental porcine skin wounds of different ages (4, 6, 8, 10, 18, 27 and 35 days) and 11 forensic porcine wound specimens (of unknown age) were evaluated. CD31-positive blood vessels and α-SMA-positive myofibroblasts were present in the granulation tissue in the experimental wounds at all time points. A significant decrease in the mean blood vessel counts was found in wounds aged 18, 27 and 35 days compared with wounds aged 6 days (P < 0.001), when assessing both the superficial and deep part of the wound bed. α-SMA expression was lower at 27 and 35 days post wounding compared with 6-18 days post wounding. Combined assessment of three parameters (mean blood vessel counts in the superficial and deep wound beds and α-SMA expression) could approximately specify the age of the wounds as either 6-18 days or ≥27 days. In two of the forensic cases a combination of the three parameters yielded results that were similar to the experimental wounds, indicating a wound age of 6-18 days or ≥27 days, respectively. In the remaining forensic cases a combination of the three parameters did not show the same expression pattern as in the experimental wounds. The results indicate that in some forensic cases the application of CD31 and α-SMA markers appeared to support the current procedure for porcine wound age estimation, but this must be combined with pathological characteristics.

Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial.

Wound healing in DFU (diabetic foot ulcer) has prolonged inflammation phase and defective granulation tissue formation. LL-37 has antimicrobial property, induces angiogenesis, and keratinocyte migration and proliferation. This study analyzes the efficacy of LL-37 cream in enhancing wound healing rate and decreasing the levels of IL-1α, TNF-α, and the number of aerobic bacteria colonization in DFU with mild infection. This study was conducted from January 2020 to June 2021 in Jakarta. Subjects were instructed to apply either LL-37 cream or placebo cream twice a week for 4 weeks. Wounds were measured on days 7, 14, 21, and 28 and processed with ImageJ. The levels of LL-37, IL-1α, and TNF-α from wound fluid were measured using ELISA. The number of aerobic bacteria colonization was counted from the isolate grown in culture. The levels of LL-37 in DFU at baseline were equally low in both groups which were 1.07 (0.37-4.96) ng/mg protein in the LL-37 group and 1.11 (0.24-2.09) ng/mg protein in the placebo group. The increase in granulation index was consistently greater in the LL-37 group on days 7, 14, 21, and 28 (p = 0.031, 0.009, 0.006, and 0.037, respectively). The levels of IL-1α and TNF-α increased in both groups on days 14 and 21 (p > 0.05). The decrease in the number of aerobic bacteria colonization was greater in the LL-37 group on days 7, 14 and 21, but greater in the placebo group on day 28 (p > 0.05). In conclusion, LL-37 cream enhanced the healing rate of DFU with mild infection, but did not decrease the levels of IL-1α and TNF-α and the number of aerobic bacteria colonization. This trial is registered at ClinicalTrials.gov, number NCT04098562.