Contralateral Wound Research Articles

Topical naltrexone potentiates cutaneous wound healing in blackbelt cichlids (Vieja maculicauda).

To evaluate the effects of topical naltrexone on wound healing in freshwater fish. 25 blackbelt cichlids (Vieja maculicauda). A randomized, controlled, experimental trial was performed, with each individual serving as its own control. Bilateral 6-mm periepaxial cutaneous wounds were created in the body-wall skin of each fish under anesthesia. Three treatment groups were as follows: topical 0.04% naltrexone in administration vehicle (iLEX ointment; iLEX Health Products) at day 0 only (n = 10), topical 0.04% naltrexone in iLEX every 72 to 96 hours (n = 10), or iLEX only every 72 to 96 hours (n = 5) for 10 total treatments. The contralateral wound was left untreated as a control. Fish were maintained in a common enclosure at 24.7 to 25.4 °C for 35 days. Macroscopic wound assessment and image collection were performed every 72 to 96 hours. On day 35, fish were humanely euthanized, and skin samples were collected for histopathology. Time to complete visual resolution of wound healing was faster (P = .002) in wounds treated every 72 to 96 hours with topical 0.04% naltrexone in iLEX (day 19.4) compared to untreated wounds (day 23.3). An interaction between treatment and day was observed (P = .002), with fish treated with 0.04% naltrexone in iLEX every 72 to 96 hours having reduced (P < .05) wound area compared to both controls and fish treated with topical 0.04% naltrexone in iLEX once. No significant differences were noted in histologic sections of wound sites examined at day 35. Fish improved earlier postsurgery and time to complete wound resolution was faster in wounds treated with topical 0.04% naltrexone in iLEX every 72 to 96 hours.

Inguinal Vascular Surgical Wound Protection by Incisional Negative Pressure Wound Therapy – A Randomized Controlled Trial – INVIPS Trial

Introduction: SSIs are a major concern in open vascular procedures involving the inguinal region and lead to increased morbidity and mortality. Negative pressure wound therapy (NPWT) has been a reliable treatment option for infected and difficult to treat chronic wounds. Prophylactic NPWT on closed incisions to prevent surgical wound complications on the other hand is a newer approach and has shown promising results but the quality of evidence can be debated. This study aims to objectively evaluate if NPWT on sutured inguinal incisions after elective vascular surgery can decrease the incidence of surgical site complications. Methods: One hundred thirty-nine patients undergoing elective open vascular surgery with inguinal incisions received either NPWT or a standard dressing. Patients with bilateral incisions randomly received a dressing on one incision and the opposite dressing on the other. The primary endpoints were SSI or other wound complications at three months, assessed by wound care experts blinded to the treatment arm and using objective wound assessment criteria (ASEPSIS-score). Statistical analysis was performed on an intention-to-treat basis. Unilateral incisions were evaluated using Fisher's exact test. Bilateral incisions were seen as not independent from each other as infections of one surgical wound incision would increase risk for infection of the contralateral wound incision and were therefore analyzed using McNemar's test. Obtained p-values from analyses in the uni- and bilateral groups were combined to an overall p-value using Fisher's method for combining p-values. Results: The incidence of SSI was reduced in the NPWT group compared to the control group (11.9% versus 29.5% in the unilateral group [n=120], 5.3% versus 26.3% in the bilateral group [n=19] respectively; combined p=0.02). No differences regarding other surgical site complications were observed between the groups. There were no reported adverse events attributable to the NPWT dressing. Conclusion: NPWT on closed inguinal vascular surgical incisions in elective patients reduces the incidence of SSI. Disclosure: Around 5% of the funding for this study came from Smith and Nephew who is the manufacturer of the Negative Pressure Wound Therapy dressing used in this study.

Adipose-derived stromal vascular fraction aids epithelialisation and angiogenesis in an animal model.

Limited data exist regarding the correlation between adipose-derived stromal vascular fraction (SVF) and wound healing. The aim of this study was to investigate the direct effect of intradermally injected SVF on full-thickness cutaneous wounds in a murine model. Wistar rats were divided into three groups (A, B and C) according to their day of euthanasia (day 7, 16 and 21). Inguinal fat pad was excised and SVF enzymatically extracted. Full-thickness cutaneous wounds were created on each side of the dorsum; SVF injected intradermally at one side while the contralateral wound served as control receiving normal saline. Postoperatively, evaluation of wound healing was performed by planimetry (percentages of wound contraction, epithelialisation and total wound healing) on days 0, 3, 5, 7, 10, 13, 16 and 21, and histology and immunochemistry (cellular infiltration score, collagen production score, neoangiogenesis and epithelial thickness) on days 7, 16 and 21. Despite the high rate of wound contraction, it was significantly lower in the SVF-treated wounds on day 21 (p=0.037). On days 13, 16 and 21, the percentages of epithelialisation were higher in the SVF-treated wounds compared with control wounds (p=0.026, p=0.048 and p=0.05, respectively). Histologically, the number of new vessels was significantly higher in the SVF-treated wounds compared with controls on days seven (p=0.028) and 16 (p=0.027). This was also confirmed by immunohistochemistry. No significant differences were found between treated and control wounds regarding cellular infiltration score, collagen production score and epithelial thickness. Data indicate that intradermally injected SVF increases angiogenesis and enhances epithelialisation in full-thickness cutaneous wounds in rats.

Autologous adipose-derived regenerative cell therapy modulates development of hypertrophic scarring in a red Duroc porcine model

BackgroundEffective prevention and treatment of hypertrophic scars (HTSs), a common consequence of deep-partial thickness injury, remain a significant clinical challenge. Previous studies from our group have shown that autologous adipose-derived regenerative cells (ADRCs) represent a promising approach to improve wound healing and, thereby, impact HTS development. The purpose of this study was to assess the influence of local delivery of ADRCs immediately following deep-partial thickness cutaneous injury on HTS development in the red Duroc (RD) porcine model.MethodsBilateral pairs of deep-partial thickness excisional wounds (2 mm depth; 58 cm2 area) were created using an electric dermatome on RD pigs (n = 12). Autologous ADRCs were isolated from the inguinal fat pad and then sprayed directly onto the wound at a dose of 0.25 × 106 viable cells/cm2. The paired contralateral wound received vehicle control. Wound healing and development of HTS were assessed over 6 months using digital imaging, quantitative measurement of skin hardness and pigmentation, and histology.ResultsData showed that ADRC treatment led to reduced scar hyperpigmentation compared to control (p < 0.05). Using the Durometer, at 2 and 6 months post-injury, skin hardness was 10–20% lower in ADRCs-treated wounds compared to control vehicle (p < 0.05). A similar trend was observed with the skin fibrometer.ADRC treatment promoted more normal collagen organization, improvement in the number of rete ridges (p < 0.01), longer elastic fiber length (p < 0.01), and reduced hypervascularity (blood vessel density; p < 0.05). ADRC treatment was associated with modulation of IL-6 expression within the wound/scar with upregulation 2 weeks after injury (wound healing phase) and downregulation at 2 months (early scarring phase) post-treatment compared to controlConclusionsThese findings support the potential therapeutic value of autologous ADRC administration for reduction of HTS development following deep-partial cutaneous injury.

Pseudorecurrence following female laparoscopic inguinal hernia repair in children

Laparascopic repair of inguinal hernias in female children can be achieved using the inversion and ligation technique in which the hernia sac is inverted into the peritoneal cavity and ligated using endoloops. This technique has been shown to reduce operative time and post-operative complications such as missed contralateral hernia, wound infection and hernia recurrence. We describe a case of a 3-month old female who underwent laparoscopic repair of bilateral inguinal hernias, and presented one year post-operatively with bilateral groin bulges. On re-operation the bulges were determined not to be true hernia recurrences, but rather pseudorecurrences of accumulated fluid distal to the ligation point after incomplete inversion. They were successfully repaired in an open fashion, without subsequent development of groin bulges.

The running butterfly suture: A novel, everting alternative to the running subcuticular technique

SOLUTION The running butterfly suture is a novel approach to closing wounds under minimal tension. The technique is performed as follows: with the wound oriented parallel to the surgeon’s body, the needle is inserted through the outside of the wound, lateral to the apex, exiting in the interior of the wound. Alternately, a buried anchoring suture, such as a simple buried suture, buried vertical mattress suture, or set-back dermal suture, may first be placed. The far wound edge is then gently reflected back with the forceps, as the needle enters at the junction where the base of the incised wound edge meets the undersurface of the dermis (Fig 1). The needle then proceeds on a diagonal course, angling upward toward the surface of the skin and outward away from the wound edge, before exiting again at the base of the undermined wound edge, further along the length of the wound than its entry point (Fig 2). The needle is then reloaded, and the procedure is repeated on the contralateral wound edge. As when using the standard running subcuticular technique, the entry point on the contralateral wound edge should be slightly backtracked from the exit point on the prior side to reduce the risk of tissue bunching. Alternating bites on each side of the wound are taken until the end of the wound is reached, at which time either a final anchoring suture may be placed or the suture material can exit lateral to the apex and be secured, leaving a well-everted wound (Fig 3).

SPLIT rectus abdominis myocutaneous double free flap for extremity reconstruction

A Mathes and Nahai type III muscle, such as the rectus abdominis muscle, can be utilized to cover two separate wounds simultaneously utilizing its dual blood supply thereby minimizing donor site morbidity and operative time. We report a case for treatment of bilateral Gustillo type IIIB lower extremity injuries treated with a single rectus abdominis muscle split into two free flaps, with one based on the deep inferior epigastric vessels and one on the superior epigastric vessels to cover the contralateral wound. In our patient, both lower extremity wounds were covered with muscle flaps from the same donor site in a single operation, salvaging both limbs with progression to unassisted ambulatory status. We show in this case report that the utilization of the vascular anatomy of the rectus muscle allows for division of the flap into two flaps, permitting preservation of the contralateral abdominal wall integrity and coverage of two wounds with a single muscle.

Effect of Negative Pressure Wound Therapy on the Elution of Antibiotics From Polymethylmethacrylate Beads in a Porcine Simulated Open Femur Fracture Model

To determine whether negative pressure wound therapy (NPWT) affects antibiotic elution in simulated femur fractures treated with antibiotic impregnated polymethylmethacrylate (PMMA) beads and whether fascial closure between beads and sponge affects the outcome. PMMA beads containing vancomycin and tobramycin were placed adjacent to bilateral corticotomies created in 20 anesthetized pigs. In 1 leg, NPWT was applied with the sponge either in direct contact with the beads or superficial to reapproximated fascia lata. The contralateral wound was conventionally closed. Vancomycin and tobramycin concentrations in wound drainage were measured every 12 hours for 72 hours, and tobramycin levels were measured in periosteal tissue obtained at 72 hours. Drainage vancomycin and tobramycin concentrations were highest at 12 hours and fell rapidly by 24 hours but remained steady thereafter. At each 12-hour interval, there were no significant differences in the vancomycin and tobramycin concentrations between NPWT and control wound drainage, although whether the fascia was closed or left open had an influence on vancomycin levels. The total vancomycin and tobramycin eluted into the drains was significantly less in the NPWT group with open fascia. The antibiotic levels measured in wound drainage remained above the minimum inhibitory concentration for common wound organisms throughout the study period. Neither NPWT nor fascial closure had a significant effect on tobramycin periosteal tissue concentrations. Concurrent application of NPWT with antibiotic impregnated PMMA beads to simulated open femur fractures in pigs did not decrease local antibiotic concentrations but did decrease the total amount of eluted vancomycin and tobramycin locally available when the fascia was left open.

A Prospective, Single-Center, Nonblinded, Comparative, Postmarket Clinical Evaluation of a Bovine-Derived Collagen With Ionic Silver Dressing versus a Carboxymethylcellulose and Ionic Silver Dressing for the Reduction of Bioburden in Variable-Etiology, Bilateral Lower-Extremity Wounds

There are numerous dressings designed to manage the overabundance of matrix metalloproteinases, while also addressing the excessive bioburden found in chronic wounds. The authors compared the efficacy of 2 such dressings: a sodium carboxymethylcellulose/1.2% ionic silver (CMC), which theoretically reduces bacteria by providing silver ions, versus a bovine native collagen (BDC)/ionic silver dressing, which also delivers silver ions in an aqueous environment. Both dressings theoretically modulate the wound bed; CMC through moist wound care and fibrin ingrowth and BDC through matrix metalloproteinase balancing. A prospective protocol was undertaken using patients as their own controls. Ten patients with bilateral venous stasis or diabetic foot ulcers were selected. One limb was randomized to treatment by either CMC or BDC, whereas the contralateral wound was treated with the other dressing. Biopsies for quantitative cultures were taken at weeks 1 and 4. Wound area was assessed at the weekly visits. The BDC wounds started with 1.0 × 10 (±1.2 × 10) bacteria, and the CMC wounds started with 1.4 × 10 (±1.3 × 10) bacteria. Over the 4-week period, the bacteria in the 3-ppm (parts per million) silver-treated wound increased 1.53 × 10, whereas in the 21-ppm silver-treated wound, the bacteria increased 1.42 × 10. The rates of closure for CMC-treated wounds was 0.79 ± 0.735 cm/wk and for BDC-treated wounds was 1.38 ± 1.44 cm/wk. Only 1 wound treated with either dressing exhibited a decrease in bacteria. Both CMC and BDC silver dressings appeared to have statistically similar efficacy regarding the rate of wound healing and little impact on the actual bioburden in chronic lower-extremity wounds. Interestingly, there was no correlation in the size of the wound and any effect on bioburden. Although the BDC dressing showed a higher absolute rate of wound closure, neither technology demonstrated a statistically significant difference in wound closure rate when corrected for initial wound size.

Human CD133 + Progenitor Cells Promote the Healing of Diabetic Ischemic Ulcers by Paracrine Stimulation of Angiogenesis and Activation of Wnt Signaling

We evaluated the healing potential of human fetal aorta-derived CD133(+) progenitor cells and their conditioned medium (CD133(+) CCM) in a new model of ischemic diabetic ulcer. Streptozotocin-induced diabetic mice underwent bilateral limb ischemia and wounding. One wound was covered with collagen containing 2x10(4) CD133(+) or CD133(-) cells or vehicle. The contralateral wound, covered with only collagen, served as control. Fetal CD133(+) cells expressed high levels of wingless (Wnt) genes, which were downregulated following differentiation into CD133(-) cells along with upregulation of Wnt antagonists secreted frizzled-related protein (sFRP)-1, -3, and -4. CD133(+) cells accelerated wound closure as compared with CD133(-) or vehicle and promoted angiogenesis through stimulation of endothelial cell proliferation, migration, and survival by paracrine effects. CD133(+) cells secreted high levels of vascular endothelial growth factor (VEGF)-A and interleukin (IL)-8. Consistently, CD133(+) CCM accelerated wound closure and reparative angiogenesis, with this action abrogated by co-administering the Wnt antagonist sFRP-1 or neutralizing antibodies against VEGF-A or IL-8. In vitro, these effects were recapitulated following exposure of high-glucose-primed human umbilical vein endothelial cells to CD133(+) CCM, resulting in stimulation of migration, angiogenesis-like network formation and induction of Wnt expression. The promigratory and proangiogenic effect of CD133(+) CCM was blunted by sFRP-1, as well as antibodies against VEGF-A or IL-8. CD133(+) cells stimulate wound healing by paracrine mechanisms that activate Wnt signaling pathway in recipients. These preclinical findings open new perspectives for the cure of diabetic ulcers.

Use of porcine renal capsule matrix as a full-thickness dermal wound-healing material in rats

To compare the utility of porcine renal capsule matrix (RCM) with porcine small intestinal mucosa (SIS) in a rat full-thickness skin wound model. Groups of rats had surgically-created wounds filled with either SIS or RCM. On each rat a contralateral wound was left unfilled (RCM-U or SIS-U). Wound diameter was measured 3, 7, 12, 17, 26 and 30 days after creation. Wound sites sampled 3, 7, 14, 28, 42 and 56 days after wound creation were numerically graded for degree of histologic change and for collagen content, based on intensity of trichrome staining. Wounds in all groups rapidly contracted to less than 50% of the original diameter within 12 days. There were no differences in wound diameter between RCM- and SIS-treated wounds at any time point, but these wounds had significantly greater (p < 0.001) diameters than their unfilled counterparts on days 7, 12 and 17. There were no differences in histologic scores or trichrome-staining scores between RCM- and SIS-treated wounds and their unfilled counterparts at any time point, except for a greater (p < 0.05) histologic score in SIS-treated wounds compared with unfilled controls on day 14. In both treatment groups an acute inflammatory response at the wound site was soon replaced by an influx of macrophages and fibroblasts. The results show that RCM is equivalent to SIS for the treatment of full-thickness wounds and that these materials may enhance wound healing in terms of wound-tissue collagenisation and maturation. These materials therefore merit further study in other wound-care models.

Effect of a Matrix Metalloproteinase Activity and TNF-Alpha Converting Enzyme Inhibitor on Intra-Abdominal Adhesions

Background: Formation of intra-abdominal adhesions depends, in part, on the activity of serine proteinases. Matrix metalloproteinases (MMP) are required for epithelialization of skin wounds but their involvement in mesothelialization of peritoneal wounds and in adhesion pathogenesis is not known. Early tumor necrosis factor-α (TNF-α) levels have been proposed to reflect propensity to adhesion formation. Objective: The impact of MMP activity and secreted TNF-α on peritoneal adhesion formation and healing was investigated through systemic administration of the synthetic broad-spectrum MMP and TNF-α-converting enzyme (TACE) inhibitor GM 6001. Methods: Female Sprague-Dawley rats of 4–6 weeks of age were injected subcutaneously daily with GM 6001 100 mg/kg (n = 12) or vehicle (n = 10) starting two days before surgery. In each rat, two standardized peritoneal wounds, 20 mm × 5 mm, were made. One peritoneal wound was sutured whereas the contralateral wound healed by secondary intention. Adhesion formation and peritoneal healing, cell proliferation, and hydroxyproline concentrations were evaluated on postoperative day 7. Results: Total serum TNF-α levels increased in vehicle-treated rats (p = 0.019) while GM 6001 treatment effectively prevented the rise in the postoperative phase (p < 0.001). No significant differences were observed in the extent of adhesion formation (p = 0.67) between control (65.0%) and GM 6001-treated (61.5%) animals, or peritoneal wound healing or cell proliferation. Hydroxyproline levels increased in the wounds (p = 0.014) but were not different between the two groups (p = 0.14). Conclusions: Lack of a striking effect of the MMP and TACE antagonist GM 6001 on postoperative adhesions suggests that MMP activity and TNF-α might not be major adhesiogenic factors.

Intrinsic electric fields promote epithelization of wounds in the newt, Notophthalmus viridescens

The lateral electric fields (LFs) in the vicinity of small wounds made in hindlimb digit tip skin of Notophthalmus viridescens have been measured and manipulated. Healing of these wounds was assessed by crystal violet staining and by histology. Paired experiments were conducted on the animals: the healing of one digit's wound was compared with healing of the contralateral digit's wound whose LF was changed from that of its contralateral wound. When currents were passed through the animal (into one wound and out of the contralateral wound) so that the LF of one wound was zero while the contralateral wound had an enhanced LF, the wounds with the enhanced LF healed more rapidly than the wounds with the zero LF. When digits on one side were treated with 30 μ M benzamil in an artificial pond water so that their wound LFs were reduced to approximately zero, and the contralateral wounds were kept in artificial pond water without benzamil so that they had normal wound LFs, there was significantly less epithelization of the benzamil-treated wounds than of the control wounds. This effect on wound healing was reversed by adding currents that restored the normal wound LFs, but not by adding currents that reversed the wound LFs to the opposite polarity. When currents were added to reverse the wound LFs on one side of the animal, leaving the contralateral wounds free of added currents, the wounds with the reversed LFs healed more poorly than the contralateral wounds with normal LFs. These results are consistent with the hypothesis that the intrinsic LFs in the vicinity of wounds promote epithelization of these wounds.

Prophylactic closed suction drainage of femoral wounds in patients undergoing vascular reconstruction

Prophylactic closed suction drainage has been advocated in a variety of surgical wounds, but its use in wounds involving vascular anastomoses has not been studied. Fifty patients undergoing lower extremity revascularization that required bilateral groin incisions were randomly assigned to have either the right or left side of the groin drained with a closed suction catheter. The contralateral wound was closed without drainage. Statistically there was no difference between wounds closed with drains and undrained wounds in the occurrence of hematomas, seromas, lymphoceles, superficial infections, subcutaneous infections, or graft infections; although serious complications were more frequent in the drained wounds. Prophylactic closed suction drainage appears to offer no advantage over closure without drainage in wounds of the groin resulting from elective vascular operations.

The effect of low-energy infra-red laser radiation on wound healing in rats

The aim of this study was to evaluate the effect of low-energy infra-red laser treatment on wound healing in rats, both histologically as well as by gross observation. In the caudal area of the back of 14 rats, identical full thickness dermal wounds were punched out bilaterally. One wound in each rat was randomly selected for laser radiation. The contralateral wound was left untreated, serving as a control. All the laser-treated wounds and the untreated control wounds healed in the same way within the same period of time. No difference was observed concerning bleeding time, nor as to the formation and loss of crust. None of the wounds showed signs of infection during the observation period. Histological examination indicated no obvious morphological difference between the laser-treated and the untreated wounds. The present study did not confirm that the use of low-energy infra-red laser radiation could improve the wound healing process.

In vivo differentiation of progenitor cells of the periodontal ligament. An experimental study using physical barriers.

The present study was designed to test the hypothesis that during regeneration of cementum, the progenitor cells from periodontal ligament must come in contact with root dentin in order to differentiate into cementoblasts. After reflecting mucoperiosteal flaps, fenestration wounds were made in the buccal cortical plates of mandibular canines in 6 beagle dogs. The exposed root surfaces were curretted to remove all cementum. The exposed root surface on one side was demineralized with citric acid while the contralateral wound had saline treatment. The exposed root surfaces were then dried and pieces of Nuclepore membrane (pore size 0.1 mu) were attached to part of the exposed root surface to prevent contact of progenitor cells with root dentin. The fenestration wounds were then covered with Millipore filter to facilitate the population of wounds by progenitor cells from the periodontal ligament. Histologic analysis was performed after 3 months of healing. In specimens where the Nuclepore membrane had remained attached to root dentin, no new cementum was seen over the membrane. At the borders of the wounds and in specimens where the Nuclepore membrane had detached from root dentin, new connective tissue attachment was consistently seen. Also, root resorption was very rarely observed in both the acid-treated and control specimens. The present findings suggest that contact with root dentin may be necessary for progenitor cell differentiation into formative cells like cementoblasts.

Wound Contraction and Zinc Absorption During Treatment with Zinc Tape

Wound healing, wound contraction and zinc absorption were studied in rats operated on with excisional wounds on each side of the dorsolateral aspects of the backs. The wounds were covered with plastic foil, plastic tape or zinc tape. The shortest healing time was seen in wounds treated with plastic foil when the contralateral wound was treated with zinc tape. Final wound contraction was decreased when the wound was treated with plastic-coated tape and zinc tape that was fixed to the surrounding skin. An increase in serum zinc concentration was seen 7 days postoperatively when the animals were treated with zinc tape and a decrease in serum zinc concentration was seen at the same time when only plastic foil was used.

創傷に対するレーザー光の治癒効果に関する研究 (第一報)

The effect of irradiation with low power laser on wound healing was studied. 80 guinea pigs were subjected to this experiment. Two open wounds, 1cm in diameter, were created on the back at the right and left side in each animals. The wound was limited to the skin (shallow wound) or excised as deep as the muscular layer (deep wound). Unilateral wound was irradiated with Argon laser (energy density 2 J/cm2 or 6 J/cm2) every day or every other day till the wound completely healed. The contralateral wound was not irradiated. From this study the wound healing was accelerated by irradiation with Argon laser average 3 days faster than that of the non-irradiated wound.

Action of Local Hydrocortisone on Spinal Cord Wounds

The general systemic effects of adrenocortical steroids is not a primary factor in the delayed healing and diminished inflammatory phenomena of wounds. A primary action of these hormones on the connective tissue elements is now accepted.1 The anti-inflammatory action of hydrocortisone may be due to the protection of the mesodermal elements from the injured tissue in the wound.2The anti-inflammatory properties have been explained by a direct action on the fibroblast cell,3interference with the elaboration of ground substance,4and, mainly, alteration in the permeability of the vessels.* The effects on inflammation and repair of local application of hydrocortisone acetate to wounds of the brain and to other parts of the body are similar. The cerebral cicatrix is diminished and proliferation of connective tissue is depressed, as compared with a contralateral wound, at corresponding periods of time, in the same animal.6 The action of local