Wound fluid inhibits wound fibroblast nitric oxide synthesis

BACKGROUND: Fibroblast-derived nitric oxide (NO) is an autocrine stimulator of collagen synthesis by wound fibroblasts. Little is known about the in vivo regulation of wound fibroblast NO synthesis. We investigated the net effect of wound environment on wound fibroblast NO production and characterized a soluble factor mediating this effect. MATERIALS AND METHODS: Wound fibroblasts and acellular wound fluid (pool of 100 Lewis rats) were isolated from subcutaneously implanted polyvinyl alcohol sponges harvested 10 days post-wounding. Fibroblasts were incubated in the presence of 10% (v/v) wound fluid. Nitrite, an index of NO synthesis, was measured in supernatants by Griess reagent. RESULTS: Wound fibroblasts spontaneously synthesize large amounts of NO. Spontaneous NO synthesis was further increased by LPS + IFN-gamma (P < 0.001). Wound fluid significantly inhibited both spontaneous and LPS plus IFN-gamma-stimulated NO synthesis (by 88 and 55%, respectively; P < 0.01). Wound fluid from 5- to 35-day-old wounds equally suppressed NO synthesis. Separation by Sephadex G-100 gel filtration identified the active factor in wound fluid to have a molecular weight of about 100 kDa. Characterization of this factor showed it to be a heat-resistant (56 degrees C, 30 min), trypsin-sensitive, and neuraminidase-resistant protein (ammonium sulfate precipitation). The isoelectric point appeared to be 7.0, as determined by ion exchange chromatography. Addition of high arginine did not restore the effect of wound fluid on fibroblast NO synthesis, suggesting that substrate is not a limiting factor. CONCLUSION: Our data demonstrate that following postoperative day 5 the wound environment contains a high molecular weight protein that inhibits NO synthesis by wound fibroblasts.     

Use of negative pressure wound therapy with instillation and a reticulated open cell foam dressing with through holes in the acute care setting

Negative pressure wound therapy with instillation and dwell time (NPWTi‐d) is an automated system used to deliver, dwell, and remove topical solutions from the wound bed. Recently, a reticulated open cell foam dressing with through holes (ROCF‐CC) was developed, which assists with wound cleansing by removing thick exudate and infectious materials. We present our experience using NPWTi‐d with ROCF‐CC on complex wounds when complete surgical debridement was inappropriate because of medical instability, recurrent non‐viable tissue, or palliative treatment plan. For all wounds, NPWTi‐d with ROCF‐CC was initiated by instilling normal saline, acetic acid, or hypochlorous acid with 2 to 10 minutes of dwell time, followed by 0.5 to 4 hours of negative pressure. Dressings were changed every 2 to 3 days. Fourteen patients with multiple comorbidities were treated for wound types including diabetic foot ulcers, necrotising fasciitis, dehisced wounds, and pressure injuries. Duration of NPWTi‐d with ROCF‐CC ranged from 1 to 15 days, and at dressing changes, wounds showed improved granulation tissue formation, less malodour, less surrounding erythema, and demarcation of healthy skin from devitalised tissue. Based on these patients, adjunctive use of NPWTi‐d with ROCF‐CC provided a practical option for improving tissue quality in wounds for patients in whom surgical debridement was not possible or desired.     

两种银敷料对慢性伤口愈合及渗液酸碱度影响的比较

目的比较两种银敷料辅助治疗慢性感染伤口的效果及对伤口渗液酸碱度的影响,以指导银敷料在慢性伤口治疗中的合理使用。方法将糖尿病足溃疡、压疮、下肢静脉溃疡、创伤性溃疡、烧伤残余创面5类慢性伤口患者104例随机分为A、B两组,每组52例。两组患者均按照统一方法评估、清洗和清创后,A组使用银离子藻酸盐敷料、B组使用纳米银敷料,分别接受30d的伤口局部辅助治疗。观察比较两组伤口治疗前及治疗后不同时间段的伤口愈合评分及渗液pH值。结果随着治疗时间的延长,两组伤口愈合计分和渗液pH值均较治疗前下降,A组患者伤口愈合计分显著优于B组(P0.01);两组伤口渗液pH值比较,差异无统计学意义(P0.05)。结论两种银敷料辅助治疗慢性感染伤口均能促进伤口愈合,但银离子藻酸盐敷料的效果更优;两种银敷料均能降低伤口渗液pH值且作用相当。     

830-nm irradiation increases the wound tensile strength in a diabetic murine model

BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the effects of low-power laser irradiation on wound healing in genetic diabetes. STUDY DESIGN/MATERIALS AND METHODS: Female C57BL/Ksj/db/db mice received 2 dorsal 1 cm full-thickness incisions and laser irradiation (830 nm, 79 mW/cm(2), 5.0 J/cm(2)/wound). Daily low-level laser therapy (LLLT) occurred over 0-4 days, 3-7 days, or nonirradiated. On sacrifice at 11 or 23 days, wounds were excised, and tensile strengths were measured and standardized. RESULTS: Nontreated diabetic wound tensile strength was 0.77 +/- 0.22 g/mm(2) and 1.51 +/- 0.13 g/mm(2) at 11 and 23 days. After LLLT, over 0-4 days tensile strength was 1.15 +/- 0.14 g/mm(2) and 2.45 +/- 0.29 g/mm(2) (P = 0.0019). Higher tensile strength at 23 days occurred in the 3- to 7-day group (2.72 +/- 0.56 g/mm(2) LLLT vs. 1.51 +/- 0.13 g/mm(2) nontreated; P < or = 0.01). CONCLUSION: Low-power laser irradiation at 830 nm significantly enhances cutaneous wound tensile strength in a murine diabetic model. Further investigation of the mechanism of LLLT in primary wound healing is warranted.     

乳猪皮生物敷料对创面愈合的影响

目的:探讨乳猪皮生物敷料促进创面愈合的机理。方法:用凡士林纱布做对照,将乳猪皮生物敷料覆盖猪皮肤缺损创面,观察创面面积、愈合时间、炎性反应及肉芽生长等组织学改变。结果:乳猪皮生物敷料较对照组凡士林纱布能加速创面愈合(P<0.01),减少炎性细胞浸润和肉芽生长。结论:乳猪皮生物敷料促进创面愈合并提高愈合的质量,并可在常温下较长时间保存,是创面修复的一种较理想的生物敷料。     

感染因素通过调控巨噬细胞表型变化影响伤口愈合的机制研究

目的观察感染因素(细菌脂多糖,LPS)如何通过调控巨噬细胞表型变化影响皮肤成纤维细胞的活化状态和功能。方法运用流式细胞技术检测巨噬细胞的活化表型;应用transwell共培养体系建立巨噬细胞和成纤维细胞共培养的模型;用MTT实验检测成纤维细胞的增殖情况;用细胞免疫荧光技术检测成纤维细胞α-SMA的表达;用ELISA实验检测细胞培养上清中Ⅰ型、Ⅲ型胶原蛋白的分泌;用q-PCR检测成纤维细胞中MMP9,MMP13的m RNA表达情况。结果 IL4诱导的M2型激活的巨噬细胞能够显著诱导皮肤成纤维细胞(HFF)高表达活化标志物α-SMA,促进成纤维细胞增殖并分泌大量Ⅰ型及Ⅲ型胶原蛋白。而感染因素LPS则能显著诱导巨噬细胞向M1表型活化,而这种活化的巨噬细胞与成纤维细胞共培养能显著抑制成纤维细胞胶原蛋白的分泌并促进基质金属蛋白酶的表达。结论感染因素能够通过调控巨噬细胞表型影响成纤维细胞的活化和功能,调控巨噬细胞的活化表型有望改善伤口愈合不良。     

The fluid handling performance of the curea P1 multipurpose dressing against superabsorbent and foam dressing technologies

Using a novel, automated robotic phantom system containing multiple wound simulants, we determined the fluid handling performance of the curea P1 multipurpose dressing vs market‐leading comparator superabsorbent and foam‐based dressings (FBDs). Specifically, we measured the retained, residual, evaporated, and (potentially occurring) spillover fluid shares for high‐ vs low‐viscosity exudate‐simulant test fluids, at 12, 24, and 30 hours postapplication of the dressings. These experiments were conducted for off‐loaded (‘prone’), non‐off‐loaded (‘supine’), and vertical (‘side‐lying’) simulated body positions. We found that the multipurpose dressing exhibited the best and most robust fluid handling performance across all the test configurations, for both the low‐ and high‐viscosity fluids. The FBD consistently showed the poorest performance compared to the other dressings, rendering it unlikely to be able to manage viscous exudates in ambulant patients (such as when applied to venous leg ulcers) as effectively as the other dressings. The superabsorbent dressing performed better than the foam dressing, but its fluid handling metrics were inferior to those of the multipurpose dressing. The current comparative quantification of the shares of retained, residual, evaporated, and spillover fluid, acquired through standardised laboratory tests, should help decision‐makers to select dressings that best meet their patient needs.     

A comparative study to evaluate the effect of honey dressing and silver sulfadiazene dressing on wound healing in burn patients

To compare the effect of honey dressing and silver-sulfadiazene (SSD) dressing on wound healing in burn patients. Patients (n=78) of both sexes, with age group between 10 and 50 years and with first and second degree of burn of less than 50% of TBSA (Total body surface area) were included in the study, over a period of 2 years (2006-08). After stabilization, patients were randomly attributed into two groups: ‘honey group’ and ‘SSD group’. Time elapsed since burn was recorded. After washing with normal saline, undiluted pure honey was applied over the wounds of patients in the honey group (n=37) and SSD cream over the wounds of patients in SSD group (n=41), everyday. Wound was dressed with sterile gauze, cotton pads and bandaged. Status of the wound was assessed every third and seventh day and on the day of completion of study. Patients were followed up every fortnight till epithelialization. The bacteriological examination of the wound was done every seventh day. The mean age for case (honey group) and control (SSD group) was 34.5 years and 28.5 years, respectively. Wound swab culture was positive in 29 out of 36 patients who came within 8 hours of burn and in all patients who came after 24 hours. The average duration of healing in patients treated with honey and SSD dressing at any time of admission was 18.16 and 32.68 days, respectively. Wound of all those patients (100%) who reported within 1 hour became sterile with honey dressing in less than 7 days while none with SSD. All of the wounds became sterile in less than 21 days with honey, while tthis was so in only 36.5% with SSD treated wounds. The honey group included 33 patients reported within 24 hour of injury, and 26 out of them had complete outcome at 2 months of follow-up, while numbers for the SSD group were 32 and 12. Complete outcome for any admission point of time after 2 months was noted in 81% and 37% of patients in the honey group and the SSD group. Honey dressing improves wound healing, makes the wound sterile in lesser time, has a better outcome in terms of prevention of hypertrophic scarring and post-burn contractures, and decreases the need of debridement irrespective of time of admission, when compared to SSD dressing.     

Preservation of the properties of elastic plasma protein plus platelet film for wound dressing

Abstract

Experimental results have previously been reported for a new biological dressing consisting of concentrated plasma proteins and platelet-rich plasma (PRP), which is named Platelet-Protein film (PPF). Based on the results of this experimental study, a clinical trial was begun to examine the usefulness of PPF. Although fresh autologous PPF is being used in the clinical trial, it is considered that the use of a preserved material prepared in advance would enable more convenient application. To verify the usefulness of preserved PPF, this preliminary study was conducted to examine the effects of fresh PPF, preserved PPF or blood clot, as control, applied to excisional skin defects in healing-impaired mice. The wound area and vascular density were analysed on day 9 after wound creation. Significant decrease of the wound size was observed in the preserved PPF and fresh PPF groups (4.2 (3.7), 2.2 (0.53)%) in comparison with that in the control group (38.5 (18.6)%, p < 0.05). Furthermore, a significant increase of the vascular density was also observed in the preserved PPF and fresh PPF groups (0.055 (0.021), 0.050 (0.019) mm²/mm²) as compared with that in the control group (0.016 (0.010) mm², p < 0.01). There was no significant difference in the effect on the wound size or vascular density between the preserved PPF and fresh PPF groups. The results showed that the properties of PPFs could be maintained for at least 1 week under appropriate storage conditions. The possibility of preservation of PPF for future use could be of practical advantage in actual clinical situations.     

功能性敷料促进供皮区创面愈合的临床研究

目的:观察功能性敷料对供皮区创面愈合的作用。方法:对48例患者行大腿外取皮,将供皮区创面分为治疗组即用功能性敷料覆盖及对照组即用凡士林纱布覆盖,分别观察治疗组和对照组供皮区创面的愈合时间。结果:创面愈合的平均时间,治疗组为(9.2±1.2)天,对照组为(13.3±2.6)天,两者比较P<0.01差异有显著意义。结论:功能性敷料能促进供皮区创面的愈合。     

Treatment of chronic ulcer with elastic plasma protein and platelet film for wound dressing

Abstract

Experimental results have previously been reported for a new biological dressing consisting of concentrated plasma proteins and platelet-rich plasma (PRP), which is named Platelet-Protein film (PPF). This study reports clinical experience using PPF produced from the patients' own blood by the original technique. Ten patients with chronic wounds underwent PPF treatment and evaluated the transcutaneous oxygen tension (TcPO₂) and vascular density. Eight of the 10 patients received a split-thickness skin graft on induced granulation tissue and have remained free from complications for more than 12 months since treatment. The TcPO₂ values significantly increased at 4 days after treatment (before 38.4 (14.1) mmHg, after 55 (19.9) mmHg, p < 0.01). The vascular density at the ulcer base increased at 14 days after treatment in all the cases. The results showed that PPF has the potential to enhance chronic wound healing.     

Influence on pressure transduction when using different drainage techniques and wound fillers (foam and gauze) for negative pressure wound therapy

Pressure transduction to the wound bed in negative pressure wound therapy (NPWT) is crucial in stimulating the biological effects ultimately resulting in wound healing. In clinical practice, either foam or gauze is used as wound filler. Furthermore, two different drainage techniques are frequently employed. One involves the connection of a non‐perforated drainage tube to the top of the dressing, while the other involves the insertion of perforated drains into the dressing. The aim of this study was to examine the efficacy of these two different wound fillers and drainage systems on pressure transduction to the wound bed in a challenging wound (the sternotomy wound). Six pigs underwent median sternotomy. The wound was sealed for NPWT using different wound fillers (foam or gauze) and drainage techniques (see earlier). Pressures between 0 and ?175 mmHg were applied and the pressure in the wound was measured using saline‐filled catheters sutured to the bottom of the wound (over the anterior surface of the heart) and to the side of the wound (on the thoracic wall). The negative pressure on the wound bed increased linearly with the negative pressure delivered by the vacuum source. In a dry wound, the pressure transduction was similar when using the different wound fillers (foam and gauze) and drainage techniques. In a wet wound, pressure transduction was better when using a perforated drainage tube inserted into the wound filler than a non‐perforated drainage tube connected to the top of the dressing (?116 ± 1 versus ?73 ± 4 mmHg in the wound at a delivered pressure of ?125 mmHg for foam, P < 0·01), regardless of the type of wound filler. Gauze and foam are equally effective at delivering negative pressure to the wound bed. Perforated drainage tubes inserted into the wound filler are more efficient than a non‐perforated drainage tubes connected to the top of the dressing. The choice of drainage technique may be particularly important in wounds with a large volume of exudate.     

Evaluation of wound healing effects of micronized acellular dermal matrix in combination with negative pressure wound therapy: In vivo study

Acellular dermal matrix (ADM) grafts can provide coverage for full-thickness skin defects and substitute for dermal defects. We tested the effectiveness of micronized ADM (mADM) as a dressing material, combined with negative pressure wound therapy (NPWT), for managing superficial wounds. We compared the wound healing effect of mADM in combination with NPWT with those of gelatin and mADM applied with a foam dressing. These therapeutic materials were applied to 36 cm² excisional wounds in a porcine full-thickness skin defect model. Wound healing kinetics and new tissue formation were assessed 10 days after the initial treatment by measuring the wound area. Collagen deposition and neovascularization were histologically evaluated. Compared with the other two groups, mADM plus NPWT combination group had a significantly larger wound area at the baseline (P = .0040), but the smallest on the 7th day (P = .0093). In addition, collagen formation and neovascularization were more histologically promoted than in the other two groups. mADM showed better results than the gelatin group but less collagen and revascularization than the combination group, and there was no significant difference in wound area. Our results show that the combination of mADM and NPWT has a synergistic wound healing effect.     

An intra‐individual surgical wound comparison shows that octenidine‐based hydrogel wound dressing ameliorates scar appearance following abdominoplasty

Hypertrophic scar formation because of surgical procedures is associated with higher levels of pain, a lower quality of life, and poor cosmetic outcome and requires more resources in follow‐up management. An octenidine‐based hydrogel has been shown to modulate immunological function in an in vitro wound model, suggesting an improved scar formation. In this prospective, randomised, observer‐blinded, and intra‐patient‐controlled study, 45 patients who underwent abdominoplasty or mastectomy with transverse rectus abdominis muscle (TRAM) flap reconstruction were given both a standard postoperative wound dressing on one wound side and an octenidine‐based hydrogel with transparent film dressing, covered with standard postoperative dressing on the other side. Four instances of hypertrophia were reported in the gel side versus 12 in the standard dressing side. Visual Analogue Scale (VAS) pain scores taken during postoperative dressing changes showed reduced scores on the gel side at all time points. Vancouver Scar Scale (VSS) scores showed improvement in the gel side at 3, 6, and 12 months postoperatively. Skin distensibility measured using a cutometer showed significantly improved measures in gel‐treated wounds, similar to measures of healthy skin. Trans‐epidermal water loss (TEWL), measured using a tewameter, showed improved values on the gel side soon after surgery, with both the control and the gel side normalising after approximately 6 months. The octenidine‐based wound dressing demonstrates improved wound healing associated with a lower incidence of hypertrophic scar formation.     

Impaired wound healing secondary to bevacizumab

Bevacizumab is a monoclonal antibody that exerts its antitumor activity by inhibiting vascular endothelial growth factor. Consequently, it suppresses endothelial cell proliferation, vascular permeability, and angiogenesis. This inhibitory effect contributes to tumour size reduction but causes wound‐healing delay, specifically during the proliferative phase, in patients receiving bevacizumab. Although surgical wound‐healing complications (WHC) associated with bevacizumab have been extensively reported, there is limited literature on peripheral WHC. More importantly, the histopathology of bevacizumab‐associated WHC has not been described. We present the histopathology findings of a non‐healing ulcer in a patient receiving bevacizumab, providing insight into the possible aetiology of this drug's adverse reaction. Furthermore, our patient's positive response to hyperbaric oxygen suggests its possible use for treatment of bevacizumab‐associated non‐healing wounds.     

重组人表皮生长因子对各类皮肤创面的疗效观察

目的:观察重组人表皮生长因子(rhEGF)对各类皮肤创面的治疗作用。方法:应用重组人表皮生长因子(rhEGF)治疗各种烧伤创面及术后创面,观察不同创面的愈合时间、愈合质量、不良反应等指标。结果:共治疗75例,总有效率100%;与对照组相比,普遍愈合时间缩短(P<0.01);创面再生上皮质量较好,瘢痕轻或无;所有病例均无不良反应。结论:在各类皮肤创面的治疗中应用rhEGF,能缩短愈合时间,提高愈合质量。保湿技术可延长rhEGF的作用时间。     

Clinical efficacy of wet dressing combined with chitosan wound dressing in the treatment of deep second-degree burn wounds: A prospective,randomised, single-blind,positive control clinical trial

To evaluate the efficacy and safety of wet dressing combined with chitosan wound dressing for deep II degree burn wounds, and provide the basis for clinical application. From October 2019 to October 2021, 80 patients with second-degree deep burn treated in the Department of burn and plastic surgery of our hospital were selected as the research objects. Patients were randomly divided into two groups. The control group (40n) was treated with wet compress, and the study group (40n) was treated with wet compress combined with chitosan wound dressing. The wound healing time, wound healing percentage and pain score were used as the effectiveness indexes, and the incidence of adverse events and serious adverse events and the detection rate of bacterial culture of wound exudates were used as the safety indexes. The efficacy and safety of the two groups were compared. The wound healing time of the study group (19.53 ± 2.74 days) was shorter than that of the control group (24.78 ± 4.86 days), the difference was significant (t = 3.571, P = 0.015). The percentage of wound healing at the 14th after treatment in the study group was higher than that in the control group (65.00% versus 37.50%) (X² = 6.054, P = 0.014). There was no significant difference in pain scores between the two groups at each time point. The scar growth was observed 3 months after wound healing. The scar score of the study group (6.00 ± 0.98) was lower than that of the control group (8.77 ± 1.19) (t = 2.571, P = 0.031). The positive rate of wound secretion culture on the 7th and 14th day was statistically significant (X² = 4.528, P = 0.033; X² = 6.646, P = 0.010), and the study group was lower than the control group (29.03% versus 81.82%; 8.11% versus 42.86%). There was no significant difference in treatment cost between the study group and the control group (1258.7 ± 223.6 versus 1248.9 ± 182.3) (t = 1.571, P = 0.071). No adverse events or serious adverse events occurred in both groups. Chitosan wound dressing can significantly shorten the time of wound healing and reduce wound pain and wound infection in patients with deep second-degree burns. And it can effectively improve the situation of scar hyperplasia, which is worthy of clinical application.     

Comparison of the efficacy and safety of povidone‐iodine foam dressing (Betafoam), hydrocellular foam dressing (Allevyn), and petrolatum gauze for split‐thickness skin graft donor site dressing

We evaluated the efficacy and safety of a povidone‐iodine (PVP‐I) foam dressing (Betafoam) for donor site dressing versus a hydrocellular foam dressing (Allevyn) and petrolatum gauze. This prospective Phase 4 study was conducted between March 2016 and April 2017 at eight sites in Korea. A total of 106 consenting patients (aged ≥ 19 years, scheduled for split‐thickness skin graft) were randomised 1:1:1 to PVP‐I foam, hydrocellular, or petrolatum gauze dressings for up to 28 days after donor site collection. We assessed time to complete epithelialisation, proportion with complete epithelialisation at Day 14, and wound infection. Epithelialisation time was the shortest with PVP‐I foam dressing (12.74 ± 3.51 days) versus hydrocellular foam dressing (16.61 ± 4.45 days; P = 0.0003) and petrolatum gauze (15.06 ± 4.26 days, P = 0.0205). At Day 14, 83.87% of PVP‐I foam dressing donor sites had complete epithelialisation, versus 36.36% of hydrocellular foam dressing donor sites (P = 0.0001) and 55.88% of petrolatum gauze donor sites (P = 0.0146). There were no wound infections. Incidence rates of adverse events were comparable across groups (P = 0.1940). PVP‐I foam dressing required less time to complete epithelialisation and had a good safety profile.     

Fetal wound healing using a genetically modified murine model: the contribution of P-selectin

Purpose

During early gestation, fetal wounds heal with paucity of inflammation and absent scar formation. P-selectin is an adhesion molecule that is important for leukocyte recruitment to injury sites. We used a murine fetal wound healing model to study the specific contribution of P-selectin to scarless wound repair.

Methods

Linear excisional wounds were created on the dorsa of E15.5 and E17.5 gestation fetuses in wild-type and P-selectin (-/-) mice (term = 19 days). Wounds were harvested at various time-points after wounding and analyzed using histology and immunohistochemistry.

Results

The E15.5 wounds in both wild-type and P-selectin (-/-) fetuses healed scarlessly and with minimal inflammation, whereas E17.5 wounds healed with fibrosis and inflammation. However, the scars of the P-selectin (-/-) wounds appeared slightly different than wild-type. There were significantly more inflammatory cells in E17.5 wild-type wounds 6 hours after injury (P < .001), but the difference was no longer significant by 24 hours. Finally, reepithelialization was slower in the E15.5 knockout wounds compared to their wild-type counterparts.

Conclusions

Absence of P-selectin delays inflammatory cell recruitment and reepithelialization of fetal wounds; however, scar formation still occurs in late gestation wounds. The contribution of specific molecules to fetal wound healing can be elucidated using murine knockout or transgenic models.