Stimulate Granulation Tissue Formation Research Articles

USING OF NEGATIVE WOUND PRESSURE THERAPY (NPWT): A CASE SERIES OF WOUND DISRUPTION AS A COMPLICATION OF A CAESAREAN SECTION

Highlights: Surgical site infection during caesarean section can cause complications, thereby increasing maternal mortality and morbidity, especially in groups at risk. VAC therapy can stimulate granulation tissue formation so that primary wound junctions occur. VAC shows its ability to close wounds entirely within 3-4 weeks. Abstract: Introduction: Wound disruption following caesarean sections is a common issue that can increase maternal mortality and morbidity. Several factors have been identified, including maternal, procedural, and antibiotic factors. The re-suturing method, primer, and secondary suture often fail, causing recurrent and delayed healing. Case Illustration: CASE 1: A 26-year-old woman, 7 days post-caesarean section, presented with a wet wound and yellowish serous fluid. Three weeks later, wound dehiscence occurred despite re-debridement and re-suturing. Subsequent installation of VAC resulted in granulation tissue and re-epithelialization. CASE 2: A 32-year-old woman, 14 days post-caesarean section, complained of weakness and pus in the surgical wound. Upon examination, a red-yellowish fluid was found, indicating wound dehiscence. Re-debridement and VAC installation led to the formation of granulation tissue and re-epithelialization. Discussion: VAC is the new wound care technique that suctions or collects excess exudate that absorbent gauze cannot accommodate. In comparison, absorbent gauze is limited in its capacity to absorb the fluid that produced in wounds. An innovation where the use of VAC, which has a negative pressure function, can stimulate granulation tissue to form and can bind the edges of the wound so that it can close naturally. Conclusion: In instances of wound disruption following surgery, such as in the case of a caesarean section, it may be prudent to contemplate re-debridement followed by re-suturing. VAC presents itself as a viable alternative for managing wound dehiscence until the formation of granulation tissue.

Hyaluronic acid based nanomedicines as promising wound healers for acute-to-chronic wounds: a review of recent updates and emerging trends

Wound healing is a highly specialized and intricate process for replacing the devitalized tissues with newer healthy tissues. Though, several conventional wound dressings are being employed for management of acute-to-chronic wounds, but substantial challenges impose by chronic wounds demand development of more efficient wound healing modalities. Hyaluronic acid has been extensively employed in designing of various wound healing nanomedicines due to its exceptional potential to stimulate granulation tissue formation and extracellular matrix remodeling. The engineered HA based nanomedicines have shown grandeur success in promoting the wound healing in different types of skin injuries (acute, chronic, diabetic, and burn wounds).

Fibronectin-derived Epiviosamines enhance PDGF-BB-stimulated human dermal fibroblast migration in vitro and granulation tissue formation in vivo.

Fibronectin (FN) is a multimodular glycoprotein that is a critical component of the extracellular matrix (ECM) anlage during embryogenesis, morphogenesis, and wound repair. Our laboratory has previously described a family of FN-derived peptides collectively called "epiviosamines" that enhance platelet-derived growth factor-BB (PDGF-BB)-driven tissue cell survival, speed burn healing, and reduce scarring. In this study, we used an agarose drop outmigration assay to report that epiviosamines can enhance PDGF-BB-stimulated adult human dermal fibroblast (AHDF) outmigration in a dose-dependent manner. Furthermore, these peptides can, when delivered topically, stimulate granulation tissue formation in vivo. A thiol-derivatized hyaluronan hydrogel cross-linked with polyethyleneglycol diacrylate (PEGDA) was used to topically deliver a cyclized epiviosamine: cP12 and a cyclized engineered variant of cP12 termed cNP8 to porcine, full-thickness, excisional wounds. Both cP12 and cNP8 exhibited dose-dependent increases in granulation tissue formation at day 4, with 600 μM cNP8 significantly enhancing new granulation tissue compared to vehicle alone. In contrast to previous studies, this study suggests that epiviosamines can be used to increase granulation tissue formation without an exogenous supply of PDGF-BB or any cell-binding peptides. Thus, epiviosamine may be useful topically to increase granulation tissue formation in acute wounds.

A topical aqueous oxygen emulsion stimulates granulation tissue formation in a porcine second-degree burn wound

BackgroundOxygen is an essential substance for wound healing. Limited studies have shown that topical oxygen can influence healing. This study evaluated the effects of a Topical Oxygen Emulsion (TOE) on burn wound healing. MethodsA porcine second-degree burn wound model was used in the study. Burn wounds were randomly assigned to TOE, vehicle control, and no-treatment (air) groups. Effects of TOE on the granulation tissue formation and angiogenesis were studied using hematoxylin and eosin histological analysis. Protein production and gene expression of types I and III collagen and vascular endothelial growth factor (VEGF) were determined using immunofluorescent staining and Reverse Transcription and Polymerase Chain Reaction (RT-PCR), respectively. ResultsThe TOE treated wounds exhibited better angiogenesis and granulation tissue formation by histology examination. The immunofluorescence staining and RT-PCR analysis demonstrated that protein production and mRNA expression of VEGF and collagen III were significantly higher in TOE treatment group than vehicle alone and air control groups, while there was no significant difference in the level of collagen I. ConclusionsOur data demonstrate that TOE enhances burn wound healing via stimulating the expression of VEGF and type III collagen and strongly indicates the potential use of TOE in wounds.

Application of a drainage film reduces fibroblast ingrowth into large‐pored polyurethane foam during negative‐pressure wound therapy in an in vitro model

Negative-pressure wound therapy (NPWT) is an advantageous treatment option in wound management to promote healing and reduce the risk of complications. NPWT is mainly carried out using open-cell polyurethane (PU) foams that stimulate granulation tissue formation. However, growth of wound bed tissue into foam material, leading to disruption of newly formed tissue upon dressing removal, has been observed. Consequently, it would be of clinical interest to preserve the positive effects of open-cell PU foams while avoiding cellular ingrowth. The study presented analyzed effects of NPWT using large-pored PU foam, fine-pored PU foam, and the combination of large-pored foam with drainage film on human dermal fibroblasts grown in a collagen matrix. The results showed no difference between the dressings in stimulating cellular migration during NPWT. However, when NPWT was applied using a large-pored PU foam, the fibroblasts continued to migrate into the dressing. This led to significant breaches in the cell layers upon removal of the samples after vacuum treatment. In contrast, cell migration stopped at the collagen matrix edge when fine-pored PU foam was used, as well as with the combination of PU foam and drainage film. In conclusion, placing a drainage film between collagen matrix and the large-pored PU foam dressing reduced the ingrowth of cells into the foam significantly. Moreover, positive effects on cellular migration were not affected, and the effect of the foam on tissue surface roughness in vitro was also reduced.

Clinicians' rationale for using a silver dressing: the French OMAg+E observational study

To describe motivations for using a silicone, silver-releasing dressing and the type of wounds treated with this dressing, and to evaluate its short-term impact on wound characteristics. A French, prospective, observational study of adult patients prescribed a soft-silicone, silver releasing dressing (MepilexAg; Molnlycke Health Care) in the community. Each participating physician was asked to include the first two consecutive patients they treated with the silver dressing, reporting patient and wound characteristics, as well as the presence of I 0 local signs compatible with wound infection (abscesses, purulent or copious exudate, erythema, increase in local warmth, pain, oedema,lymphangitis or satellite adenitis, malodour and delayed wound healing). Clinicians were also asked to select from a list their rationale for prescribing the silver dressing for each patient, including treating a wound infection, to stimulate granulation tissue formation, to promote wound healing, to reduce wound exudate, and to decrease wound pain. Local and general treatment were also reported. Overall, 794 patients (58% females), with a mean age of 69.0 ± 15.4 years, were included by 128 general practitioners, 51 dermatologists and 63 vascular specialist. Sixty-seven per cent were venous leg ulcers (VLUs), 26% were acute wounds (post-traumatic, surgical, burn wounds and animal bites) and 6.3%were other chronic wounds (pressure ulcers, diabetic foot ulcers and oncology wounds). On average 3.7 ± 1.5 local signs of infection were present and mean pain intensity (on a visual analogue scale) was 50± 24mm.According to prescribers, infection and healing delay were the primary rationale in 82% of cases,with oral antibiotics started concurrently in 19% of these wounds. Patients were followed-up at a median of 19 days, by which time all wound parameters were documented as significantly improved. Tolerability and efficiency of the silver dressing was considered as 'good'/'very good' in more than 97% of cases. While there are some variances with the French reimbursement indication, for the clinicians surveyed in this study, the primary rationale for prescription of a silver dressing was treatment of a possible wound infection. Although this indication might not always be clinically funded, based on wound characteristics, the short-term impact of this prescription in this series was favourable.

Postischemic Lower Extremity Wounds Treated with and without Negative Pressure Dressing

Background: Vacuum-assisted dressing is a noninvasive closure system of the wound, which makes localized and controlled negative pressure. Its mechanical tension reduces edema, stimulates granulation tissue formation and angiogenesis, and prepares the wound bed for closure. In this study, a patient has been presented, who suffered from serious lower extremity wounds due to arterial emboli, one of her wounds has been treated with vacuum-assisted dressing and the other with conventional dressing to evaluate the efficacy of vacuum-assisted dressing in acute ischemic wounds. Methods: A 65-year-old female patient was admitted to the emergency clinic, due to complaint of severe pain in her right lower extremity which suggested an acute arterial occlusion. She immediately underwent an embolectomy operation; however, a few days later, severe ischemia on the leg and foot became appearant. All of the necrosis was sharply debrided under sterile conditions in the operating room, and then lower leg wound was covered with vacuum-assisted dressing, also calcaneal wound was dressed with silver sulphadiazine. Results: Eighteen days after the first dressing with negative pressure, distal leg wound became ready for closure, whereas, enough granulation tissue over the calcaneal area developed merely thirty-four days later. Calcaneal wound closed spontaneously within fifty-three days. Conclusions: When dealing with this experience, using the negative pressure dressing in patient with severe lower limb wounds following arterial emboli, accelerates wound healing by means of developing the granulation tissue, and rapidly prepares the wound for closure, so it may reduce the risk of amputation.

The Influence of Low and High Pressure Levels during Negative-Pressure Wound Therapy on Wound Contraction and Fluid Evacuation

Negative-pressure wound therapy promotes healing by drainage of excessive fluid and debris and by mechanical deformation of the wound. The most commonly used negative pressure, -125 mmHg, may cause pain and ischemia, and the pressure often needs to be reduced. The aim of the present study was to examine wound contraction and fluid removal at different levels of negative pressure. Peripheral wounds were created in 70-kg pigs. The immediate effects of negative-pressure wound therapy (-10 to -175 mmHg) on wound contraction and fluid removal were studied in eight pigs. The long-term effects on wound contraction were studied in eight additional pigs during 72 hours of negative-pressure wound therapy at -75 mmHg. Wound contraction and fluid removal increased gradually with increasing levels of negative pressure until reaching a steady state. Maximum wound contraction was observed at -75 mmHg. When negative-pressure wound therapy was discontinued, after 72 hours of therapy, the wound surface area was smaller than before therapy. Maximum wound fluid removal was observed at -125 mmHg. Negative-pressure wound therapy facilitates drainage of wound fluid and exudates and results in mechanical deformation of the wound edge tissue, which is known to stimulate granulation tissue formation. Maximum wound contraction is achieved already at -75 mmHg, and this may be a suitable pressure for most wounds. In wounds with large volumes of exudate, higher pressure levels may be needed for the initial treatment period.

Evaluation of Formation of Granulation Tissue Caused by Metallic Stent Placement in a Rat Urethral Model

To evaluate the feasibility of metallic stent placement and the formation of granulation tissue caused by stent placement in a rat urethral model. A bare self-expanding metallic stent was inserted in the urethra under fluoroscopic guidance in 20 male Sprague-Dawley rats. Ten rats were euthanized at 4 weeks (group A), and the other 10 were euthanized at 8 weeks after stent placement (group B). Stenosis diameter, number of epithelial layers, degree of inflammatory cell infiltration, thickness of submucosal fibrosis, and percentage of granulation tissue area were assessed. Stent placement was technically successful in all rats. Urethrograms showed perforation in three rats, partial migration in three, and stone formation in four. Granulation tissue formation was observed in all rats at the stent-implanted urethra, and the average percentage of granulation tissue area accounted for 41% and 45% of the original urethral lumen area in groups A and B, respectively. Urethrograms and urethral specimens showed significantly less stenosis diameter, less thickness of submucosal fibrosis, and lower percentage of granulation tissue area in the proximal urethra than in the distal urethra in both groups (P < .05). Histologic results demonstrated significantly fewer epithelial layers in group B compared with group A (P = .028). Placement of a self-expandable metallic stent proved to be feasible in the rat urethra and an efficient approach to stimulate granulation tissue formation as a potential model for reproducing the mechanisms of restenosis.

A new method for sternal closure after vacuum-assisted therapy in deep sternal infections following cardiac surgery

The treatment of nonhealing and infected sternotomies following cardiac surgery is a challenging task, with increased rates of mortality and morbidity, as well as high costs. Local vacuum therapy (VAC. sytem) permits the treatment of deep sternal infections due to continuous aspiration and a sealed dressing which stimulates granulation tissue formation. Aggressive vacuum-assisted closure treatment of the sternum in postoperative deep wound infection enhances sternal preservation and the speed of potential rewiring. After some weeks of VAC-therapy a complete preparation of the substernal structures is necessary. In this context laceration of the right ventricle is a rare, but life-threatening complication. We present a new technique for sternal closure after vacuum-assisted wound treatment using Nitinol clips which can prevent these severe complications. Without any preparation of the substernal tissue the clips can be inserted in the parasternal space with consecutive proper stabilization of the sternum. This new method represents an easy, low-cost and complication-free procedure.

New Method for Sternal Closure After Vacuum-Assisted Therapy in Deep Sternal Infections After Cardiac Surgery

The treatment of nonhealing and infected sternotomies after cardiac surgery is a challenging task with increased rates of mortality and morbidity, as well as high costs. A local vacuum therapy (ie, the vacuum-assisted closure system) permits the treatment of deep sternal infections due to continuous aspiration and a sealed dressing that stimulates granulation tissue formation. Aggressive vacuum-assisted closure treatment of the sternum in postoperative deep wound infection enhances sternal preservation and the speed of potential rewiring. After some weeks of vacuum-assisted closure therapy, a complete preparation of the substernal structures is necessary. In this context, laceration of the right ventricle is a rare but life-threatening complication. We describe a new technique for sternal closure after vacuum-assisted wound treatment using Nitinol clips (Praesidia, Bologna, Italy), which can prevent these severe complications. Without any preparation of the substernal tissue the clips can be inserted in the parasternal space with consecutive proper stabilization of the sternum. This new method represents an easy, low-cost and complication-free procedure.

A new technique for the treatment of delayed sternotomy healing: the vacuum therapy.

The treatment of nonhealing and infected sternotomies after cardiac surgery is a challenging task, with its increased rates of mortality, morbidity, and costs. Local vacuum therapy (V.A.C. system) allows treatment of local infections, thanks to continuous aspiration and the sealed dressing that stimulates granulation tissue formation. The purpose of this clinical investigation was to evaluate vacuum therapy in cardiac surgery for achieving healing of delayed sternotomy closure after cardiac surgery. From January 1998 to December 2002, 7 patients who underwent coronary artery bypass surgery under cardiopulmonary bypass by median sternotomy approaches presented a nonhealing infected sternal surgical wound that was treated with local vacuum therapy. Aspiration maintained between -125 mm Hg and -200 mm Hg was carried out on the entire surface of the wound with a sponge connected hermetically to an aspiration system. The treatment was associated with antibiotic therapy adapted to the results of bacteriological studies of the aspirates. All patients with delayed sternotomy closure healed in approximately 8 weeks (2-12 weeks) with the exception of one patient who died of multiorgan failure after a satisfactory muscular pectoral flap. Treatment was possible with vacuum therapy alone (n = 2), with vacuum therapy in association by second intention with a skin graft (n = 1), or both with a muscular pectoral flap (n = 4). Sternal stability appears to be an important factor for achieving satisfactory and complete healing. This new therapy offers an alternative to the classic treatment of infected sternotomies in cardiac surgery, especially in preparing rewiring and muscular flaps for complicated cases with sternal instability or alone. The treatment must be instituted early to be more effective.

Contribution of circulating IGF-I to wound repair in GH-treated rats.

Systemic administration of growth hormone (GH) stimulates granulation tissue formation, increases collagen deposition, improves the breaking strength of incisional wounds, and decreases donor-site healing times in burn patients. The possible role for circulating IGF-I in mediating this effect of growth hormone has not been investigated. To assess the relative effects of systemic IGF-I and GH on dermal repair, incisional wounds were created on the backs of male Sprague-Dawley rats treated with GH, or IGF-I or a combination of GH and IGF-I. After 7 days of treatment, wound strips were taken for wound strength and immunohistochemical analysis. Uninjured skin and liver samples were collected for mRNA analysis and plasma samples were taken at the completion of the experiment to determine circulating IGF-I levels. Increased circulating IGF-I levels and increased weight gain were observed only in the IGF-I and IGF-I+GH treatment groups, although steady-state igf-I levels were not altered in liver and uninjured skin after 7 days in any treatment group. IGF-I treatment had no positive effects on wound repair. Wound strength was increased with GH treatment only and associated with an increase in the intensity of IGF-I immunostaining in the granulation tissue of GH-treated animals. In line with the wound strength data, co-administration of IGF-I resulted in the decreased intensity of IGF-I immunostaining. We conclude that the GH-stimulated increase in wound strength is not mediated via endocrine-derived IGF-I and that only locally produced IGF-I acting in an autocrine or paracrine fashion contributes to the regulation of the wound repair process.

The role of airway stents in the management of pediatric tracheal, carinal, and bronchial disease.

A variety of stents are available to aid in the management of complex tracheal, carinal and bronchial stenoses. We reviewed our multi-institutional experience with airway stents in children. Thirty-three children (age, 13 days-18 years) from four institutions have had a total of 40 stents placed to aid in the management of complex airway stenoses. Three stent types were utilized: 29 silastic stents, five expandable metal stents and six customized carinal stents (four patients had two stents and one patient had four stents). Thirty children had tracheal stents, six children had bronchial stents, and two infants had carinal stents (three children had stenting of more than one area and two had stenting of all three locations). Twenty-eight patients (age, 5 months-18 years; mean, 8.06 years; SEM, 1.13 years) had stents placed after a variety of airway reconstructive procedures. Four underwent stenting in a non-operative setting and one as preoperative stabilization. Twenty-seven patients survived. One patient died early due to bleeding. Five patients died late: two due to bleeding, one from mediastinitis, and two patients with functional airways died late from unrelated problems. Complications are related to stent type and location. Carinal stents can migrate; several techniques are available to help manage this problem. Wire stents are essentially non-removable requiring periodic dilation. Silastic stents stimulate granulation tissue formation requiring periodic bronchoscopic removal. Tracheal stenting can aid in the management of pediatric airway problems. Complications are common, but can be managed with appropriate intervention.

Growth hormone stimulates granulation tissue formation and insulin-like growth factor-I gene expression in wound chambers in the rat.

It has been reported that GH stimulates fibroblast growth and wound healing. In the present study we measured the effect of locally applied GH on insulin-like growth factor (IGF-I) mRNA concentrations and granulation tissue formation in wound cylinders, implanted s.c. Four stainless-steel wiremesh cylinders were implanted s.c. in the back of male rats (280 g). Each cylinder was then injected every day with either 0.014 or 0.14 U human GH, or vehicle only. Ingrown granulation tissue and wound fluid was obtained on day 17 after implantation. The wet weight of granulation tissue was determined and concentrations of IGF-I mRNA in the tissue were measured by solution hybridization/RNAase protection assay. Similar assays were used to measure the levels of IGF-I receptor mRNA and GH receptor mRNA, while the IGF-I concentration in wound fluid and serum was determined by radioimmunoassay (RIA) after acid-ethanol extraction. The concentrations of IGF-I mRNA in ingrown granulation tissue as well as the wet weight of this tissue were significantly higher in the GH-treated cylinders. There was no significant effect of GH on IGF-I receptor mRNA and GH receptor mRNA levels. Consistent with the results of previous studies, wound fluid IGF-I levels were lower than serum IGF-I levels, but no significant difference was found between the GH-treated cylinders and the control cylinders. The results of the present study show that GH stimulates granulation tissue formation and increases the concentration of IGF-I mRNA in the ingrown granulation tissue.