Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury.

AIM: We aimed to confirm the inhibitory effect of nicotinamide on fibrotic scar formation following spinal cord injury in mice using functional metabolomics. METHODS: We proposed a novel functional metabolomics strategy to establish correlations between gene expression changes and metabolic phenotypes using integrated multi-omics analysis. Through the integration of quantitative metabolites analysis and assessments of differential gene expression, we identified nicotinamide as a functional metabolite capable of inhibiting fibrotic scar formation and confirmed the effect in vivo using a mouse model of spinal cord injury. Furthermore, to mimic fibrosis models in vitro, primary mouse embryonic fibroblasts and spinal cord fibroblasts were stimulated by TGFß, and the influence of nicotinamide on TGFß-induced fibrosis-associated genes and its underlying mechanism were examined. RESULTS: Administration of nicotinamide led to a reduction in fibrotic lesion area and promoted functional rehabilitation following spinal cord injury. Nicotinamide effectively downregulated the expression of fibrosis genes, including Col1α1, Vimentin, Col4α1, Col1α2, Fn1, and Acta2, by repressing the TGFß/SMADs pathway. CONCLUSION: Our functional metabolomics strategy identified nicotinamide as a metabolite with the potential to inhibit fibrotic scar formation following SCI by suppressing the TGFß/SMADs signaling. This finding provides new therapeutic strategies and new ideas for clinical treatment.

Comparison of the wound healing and complications of zipper type closure adhesive tape and stapler for surgical wound suture: A randomized control, single-centre, open-label trial.

Xkin closure is a newly developed medical suture device for lacerations and surgical wounds that can reduce scarring, pain and the risk of infection compared with conventional sutures or staplers. A randomized controlled study was performed to compare the wound healing effects and complications of Xkin closure with stapler closure. Fifty patients who underwent robot-assisted radical prostatectomy for prostate cancer were randomly assigned. Only the wound above the navel, which was extended to take out the prostate was targeted. The wound was examined at 2, 6 and 12 weeks after surgery, and the modified Vancouver Scar Scale (mVSS), scar height and side effects were assessed with a 3D skin analyser. Forty-six patients (23 Xkin, 23 Stapler) were analysed. The mVSS scores, vascularity and pliability were significantly lower in the Xkin group compared with the stapler group at the 12-week follow-up. No significant differences in the maximum peak and depth of the scars were detected between the two groups using 3D photographs at 12 weeks. Xkin is an effective wound closure method for improving scar outcomes. This method is expected to be widely used for surgical wounds and lacerations caused by trauma in daily life.

Fast absorbing gut sutures in dermatologic surgery: a systematic review and meta-analysis.

INTRODUCTION: Fast gut cutaneous sutures have become more prominent due to their low tissue reactivity, rapid absorption, and elimination of suture removal visits. It is not known how fast gut sutures compare to other closure modalities. METHODS: A comprehensive literature review was conducted to identify randomized controlled trials comparing fast gut sutures to alternative closure methods during dermatologic surgery. Data collected included patient and physician assessed cosmetic outcome as well as standardized complication rates. RESULTS: Six studies were included in final analysis and reported on 208 patients. Fast gut sutures were associated with lower physician opinions of final scar when compared to polypropylene sutures (SMD 0.438; 95% CI 0.082 to 0.794). No differences existed between physician opinion of fast gut sutures and cyanoacrylate tissue adhesive (SMD - 0.024; 95% CI - 0.605 to 0.556). Complications with fast gut suture placement were rare, and included infection, dehiscence, and hematomas. Fast gut sutures were less likely to experience wound dehiscence than tissue adhesive (p = 0.01). CONCLUSION: If no contraindications to polypropylene sutures exist, they may provide superior cosmetic outcomes compared to fast gut sutures. Further research is required to better quantify cosmetic outcomes and optimal use of fast gut sutures.

Implementation of delayed intervention in open approach rhinoplasty for patients with supratip scarring.

INTRODUCTION: The columellar incision and dissection which were integral steps in open rhinoplasty play a crucial role in achieving optimal results. However, scarring in the supratip region may pose challenges to skin circulation, potentially leading to complications such as flap loss. OBJECTIVES: This study aims to establish the safety and efficacy of the open rhinoplasty technique as a viable alternative for patients with substantial scars in the supratip region typically addressed using the closed rhinoplasty technique. PATIENTS AND METHODS: Patients with scars on the tip or supratip region were operated clinic between February 2010 and March 2023. To mitigate the risk of tip necrosis, a meticulous two-step delay approach was employed. In the initial outpatient procedure, performed under local anesthesia, we opted for a columellar incision. Subsequently, the columellar arteries were identified and cauterized to facilitate the delay procedure. Following a ten-day interval, all patients underwent standard open rhinoplasty. RESULTS: The columellar artery delay procedure proved instrumental in executing successful open rhinoplasty without compromising skin circulation between the scarred supratip and columellar incision line. CONCLUSION: Our findings suggest that the columellar delay procedure effectively prevents flap loss in open rhinoplasty patients with scars in the supratip and columellar regions. This brief outpatient intervention, lasting approximately ten minutes, provides a reliable method for adopting the open approach in primary rhinoplasty cases, irrespective of prior scarring. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Emerging Technologies.

In this article, an array of new developments in burn care, from diagnosis to post-burn reconstruction and re-integration, will be discussed. Multidisciplinary advances have allowed the implementation of technologies that provide more accurate assessments of burn depth, improved outcomes when treating full-thickness burns, and enhanced scar tissue management. Incorporating these new treatment modalities into current practice is essential to improving the standard of burn care and developing the next generation of burn wound management methodologies.

A novel surgical correction using a combination of wave-like incision and Z-axis Z-plasty for congenital constriction band syndrome.

BACKGROUND: A congenital constriction band (CCB) is a relatively common anomaly among limb malformations. However, the number of cases treated at a given center is limited and differences in techniques used by surgeons at each facility have a significant impact on the treatment outcomes. Several surgical methods have been reported, but a standard technique that yields consistent satisfactory results is still needed. Here, we introduce a novel technique for the treatment of CCB syndrome that uses a combination of wave-like skin incision and Z-axis Z-plasty. PATIENTS AND METHODS: A wave-like incision was used for skin incision with the goals of achieving an accordion effect and a less noticeable post-operative scar. After the fibrous constriction band was completely excised, a Z-plasty of sufficient size in the Z-axis direction was performed on the dermis-inclusive adipose tissue. For over 10 years, this technique was applied to 11 sites in 6 patients. A retrospective study of the characteristics of these cases was performed, including age at surgery, gender, type of deformity, degree of constriction, types of examination, number of surgeries, and post-operative outcomes. RESULTS: In all patients, a normal contour of the limbs was achieved and the hourglass-like deformity caused by the constriction band was satisfactorily improved. No additional corrective surgeries were needed, there was no abnormal growth of the treated limbs, and scarring was aesthetically acceptable in all cases. CONCLUSION: The novel technique described here uses deep subcutaneous fat to correct the hourglass-like deformity and restores a normal limb contour, while the wave-like skin incision minimizes post-operative scarring.

'Rosebud' inset of DIEP flap in delayed breast reconstruction for consistent projection, lateral flow, and ptosis.

Here we describe a template of DIEP flap inset that prioritises projection, lateral flow and natural ptosis; key elements of an aesthetically successful delayed breast reconstruction. By not excising the full length of the mastectomy scar, and preserving the scar laterally, we increase the 3-dimensional aesthetic of the breast, moving the final reconstructed breast aesthetic further away from an unintentional 2-dimensional resurfacing. Through controlling the initial take-off around the whole circumference of the breast footprint, a favourable and durable breast conus is consistently achieved. This technique employs designated segments of comparatively more rigid irradiated mastectomy skin flaps, to positively influence reconstructed breast aesthetics at the time of flap inset. Conceptually, this reminds the authors of how the green sepals of a rose shape the bud of petals.

Graftless Syndactyly Release.

Syndactyly release aims to address skin deficits by resurfacing web spaces and sides of digits to allow independent digital motion while minimizing the risk of web creep and scar contractures. Conventional methods include the use of a dorsal and interdigitating flaps with full-thickness skin grafts. More recently, there have been several descriptions of "graftless" syndactyly release without skin grafts, thus avoiding a further (usually distant) donor site. However, the indications of when and when not to use these techniques remain unclear. In addition, the inevitable scarring from extra recruitment of local adjacent skin is perhaps underemphasized. In this article, we revisit the trilobed flap technique which serves to balance the amount of skin needed for resurfacing digits while minimizing local donor site scarring. The geometry and nuances of the flap inset are illustrated in detail to guide those embarking on this technique. The trilobed syndactyly release technique is a reproducible, safe, and reliable method for the release of simple syndactyly.

Rapid formed temperature-sensitive hydrogel for the multi-effective wound healing of deep second-degree burn with shikonin based scar prevention.

Burns are a significant public health issue worldwide, resulting in prolonged hospitalization, disfigurement, disability and, in severe cases, death. Among them, deep second-degree burns are often accompanied by bacterial infections, insufficient blood flow, excessive skin fibroblasts proliferation and collagen deposition, all of which contribute to poor wound healing and scarring following recovery. In this study, SNP/MCNs-SKN-chitosan-ß-glycerophosphate hydrogel (MSSH), a hydrogel composed of a temperature-sensitive chitosan-ß-glycerophosphate hydrogel matrix (CGH), mesoporous carbon nanospheres (MCNs), nitric oxide (NO) donor sodium nitroprusside (SNP) and anti-scarring substance shikonin (SKN), is intended for use as a biomedical material. In vitro tests have revealed that MSSH has broad-spectrum antibacterial abilities and releases NO in response to near-infrared (NIR) laser to promote angiogenesis. Notably, MSSH can inhibit excessive proliferation of fibroblasts and effectively reduce scarring caused by deep second-degree burns, as demonstrated by in vitro and in vivo tests.

An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars.

Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-ß1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.

Fibrin Glue Coating Limits Scar Tissue Formation around Peripheral Nerves.

Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to limit scarring around peripheral nerves. Thirty rats were divided into three groups: glutaraldehyde-induced sciatic nerve injury treated with FG (GA + FG), sciatic nerve injury with no treatment (GA), and no sciatic nerve injury (Sham). Neural regeneration was assessed with weekly measurements of the visual static sciatic index as a parameter for sciatic nerve function across a 12-week period. After 12 weeks, qualitative and quantitative histological analysis of scar tissue formation was performed. Furthermore, histomorphometric analysis and wet muscle weight analysis were performed after the postoperative observation period. The GA + FG group showed a faster functional recovery (6 versus 9 weeks) compared to the GA group. The FG-treated group showed significantly lower perineural scar tissue formation and significantly higher fiber density, myelin thickness, axon thickness, and myelinated fiber thickness than the GA group. A significantly higher wet muscle weight ratio of the tibialis anterior muscle was found in the GA + FG group compared to the GA group. Our results suggest that applying FG to injured nerves is a promising scar tissue prevention strategy associated with improved regeneration both at the microscopic and at the functional level. Our results can serve as a platform for innovation in the field of perineural regeneration with immense clinical potential.

The anterior neck scar outcomes of conventional thyroidectomy using a wound protector: a multicenter double-blinded randomized controlled trial.

PURPOSE: This study aimed to investigate the effectiveness of a novel wound protector in enhancing the cosmetic outcomes of thyroidectomy. MATERIAL AND METHODS: This multicenter, double-blinded randomized controlled trial enrolled 129 patients undergoing open thyroidectomy. The patients were divided into a wound protector group and a control group. Subjective patient assessments were conducted, measuring wound satisfaction, pain, and itchiness. Additionally, blinded observers evaluated scars using the Vancouver Scar Scale. RESULTS: The Vancouver Scar Scale revealed significant advantages for the wound protector group, demonstrating improvements in pigmentation ( P =0.002), vascularity ( P =0.014), pliability ( P =0.001), and height ( P =0.001). CONCLUSION: The thyroid wound protector offers a potential to improve postoperative cosmetic outcomes. Further research is warranted to explore patient experiences and optimize the application of this innovative wound protector across diverse surgical contexts.

Adipose perforator flaps without skin donor site: "in between" single scar approach for reconstruction of small peripheral breast defects after lumpectomy.

In breast conserving surgery, the reconstruction of defects in small breasts where volume displacement techniques are not feasible can be challenging. In contrast, patients with bigger breasts may not wish to undergo major breast remodeling surgery or breast symmetrization procedures. In such cases, volume replacement techniques can be beneficial, but these leave additional scars and are time consuming. The authors propose an "in between" single scar approach to perform both lumpectomy and reconstruction of small peripheral breast tumors. This approach reduces morbidity and operating time compared with standard volume replacement techniques. The tumors are resected from below, guided by wire, using an incision in the lateral breast crease or inframammary fold, depending on their location. The same incision is used to raise an adipose or adipofascial flap based on perimammary perforators, lateral thoracic artery perforator flap (LTAP), lateral intercostal artery perforator flap (LICAP), or anterior intercostal artery perforator flaps (AICAP) flaps, without skin donor site. Between March and November 2022, eight patients underwent this procedure. In four cases LICAP flap was used; in three-AICAP flap was chosen; and in one-LTAP perforator flap was used. Clear surgical margins were achieved in all cases. The average follow-up time was 9.9 months, during which no local recurrences were detected. All flaps survived. Two patients experienced seromas at the donor site, and an organized hematoma was also reported. This approach represents a viable alternative to volume displacement techniques or no reconstruction for small peripheral lumpectomy defects.

Botulinum toxin type A inhibits M1 macrophage polarization by deactivation of JAK2/STAT1 and IκB/NFκB pathway and contributes to scar alleviation in aseptic skin wound healing.

The non-neuronal and non-muscular effects of botulinum toxin type A (BTXA) on scar reduction has been discovered. This study was designed to investigate the effects of BTXA on macrophages polarization during the early stage of skin repair. A skin defect model was established on the dorsal skin of SD rats. BTXA was intracutaneous injected into the edge of wound immediately as the model was established. Histological examinations were performed on scar samples. Raw 264.7 was selected as the cell model of recruited circulating macrophages, and was induced for M1 polarization by LPS. Identify the signaling pathways that primarily regulated M1 polarization and respond to BTXA treatment. Application of BTXA at early stage of injury significantly reduced the scar diameter without delaying wound closure. BTXA treatment improved fiber proliferation and arrangement, and inhibited angiogenesis in scar granular tissue. The number of M1 macrophages and the levels of pro-inflammation were decreased after treated with BTXA in scar tissues. LPS activated JAK2/STAT1 and IκB/NFκB pathways were downregulated by BTXA, as well as LPS induced M1 polarization. At early stage of skin wound healing, injection of BTXA effectively reduced the number of M1 macrophages and the levels of pro-inflammatory mediators which contributes to scar alleviation. BTXA resisted the M1 polarization of macrophages induced by LPS via deactivating the JAK2/STAT1 and IκB/NFκB pathways.

Aesthetic Perceptions Regarding a Thyroidectomy Scar and Transvestibular Approach in Brazil.

OBJECTIVE: We investigated motivation levels across the general Brazilian population and subgroups and their willingness to spend for surgery without a cervical scar. METHODS: This random-sample survey was performed by a specialized third-party research institute. In this study, we created a hypothetical thyroidectomy scenario, and the transcervical and transoral endoscopic thyroidectomy vestibular approach (TOETVA) were used. The survey included sociocultural data and questions regarding participants' surgical preferences. RESULTS: Data were obtained from 1250 participants; 42.4% were of the opinion that a cervical scar affects social or professional life. Young and childless women were most likely to be affected (p <0.001). All respondents accepted the transoral approach to avoid cervical scarring. However, 30.7% and 31.9% of respondents maintained their preference for TOETVA despite understanding the risks of a hypothetical increase in complications and unfavorable oncological outcomes and 98.6% were of the opinion that this approach was likely associated with greater postoperative pain. Only 16.2% were unwilling to spend for TOETVA. The variable that most affected patients' willingness to spend was a salary greater than 10 Brazilian minimum wages (odds ratio 9.797, 95% confidence interval, p <0.005). Upper class respondents were 10 times more likely to spend for TOETVA than lower class patients. CONCLUSION: This study highlights patients' interest in TOETVA. Cervical scar perception is affected by concerned about appearance, particularly in certain societal subgroups. Our study population showed significant motivation to undergo TOETVA, which was emphasized by their acceptance of the complication rate, poor postoperative outcomes, greater postoperative pain, and willingness to spend on surgery with an invisible scar. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3862-3867, 2024.

Bilateral Costal Cartilage Harvest for Auricle Reconstruction: A New Technique to Prevent Postoperative Thoracic Deformity.

HYPOTHESIS: Unilateral costal cartilage harvesting (UCCH) for auricle reconstruction in children tends to cause thoracic deformities. Therefore, our study aimed to develop a novel bilateral costal cartilage harvesting (BCCH) method to prevent and reduce thoracic deformities. METHODS: Patients with unilateral microtia who underwent either UCCH (n = 50) or BCCH (n = 46) were enrolled in this study. The grafts for the BCCH group were harvested from the 6th costal cartilage of the ipsilateral hemithorax and the 7th and 8th cartilage from the other hemithorax. Computed tomography and physical examination were performed to identify any physical deformities in the chest contours post-surgery. The cosmetic appearance of the thoracic scars post-surgery was evaluated using the Scar Cosmesis Assessment and Rating Scale (SCAR) and Visual Analogue Scales (VAS cosmetic). The numerical rating scale (NRS) was used to quantify the pain in donor sites. The reconstructed ears were assessed during the follow-up period. RESULT: None of the patients in the BCCH group developed thoracic deformities, while 16 patients within the UCCH group developed mild (n = 12) or severe (n = 4) thoracic deformities (p < 0.001). The SCAR (3.09 vs. 2.92, p = 0.580) and VAS scores (0.96 vs. 0.90, p = 0.813) did not differ significantly between the two groups. For both treatment arms, the NRS scores were highest on the first-day post-surgery and gradually dropped over the 10 days. No significant differences were found in the NRS scores and the aesthetic outcomes of the reconstructed ears between the two groups. CONCLUSION: The BCCH method effectively reduced the incidence of thoracic deformity at the donor site without increasing postoperative pain and cosmetic concerns for patients. It could be used clinically to improve patient outcomes of costal cartilage grafts. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3572-3580, 2024.

Current Approaches to Wound Repair in Burns: How far Have we Come From Cover to Close? A Narrative Review.

Burn injuries are a significant global health concern, with more than 11 million people requiring medical intervention each year and approximately 180,000 deaths annually. Despite progress in health and social care, burn injuries continue to result in socioeconomic burdens for victims and their families. The management of severe burn injuries involves preventing and treating burn shock and promoting skin repair through a two-step procedure of covering and closing the wound. Currently, split-thickness/full-thickness skin autografts are the gold standard for permanent skin substitution. However, deep burns treated with split-thickness skin autografts may contract, leading to functional and appearance issues. Conversely, defects treated with full-thickness skin autografts often result in more satisfactory function and appearance. The development of tissue-engineered dermal templates has further expanded the scope of wound repair, providing scar reductive and regenerative properties that have extended their use to reconstructive surgical interventions. Although their interactions with the wound microenvironment are not fully understood, these templates have shown potential in local infection control. This narrative review discusses the current state of wound repair in burn injuries, focusing on the progress made from wound cover to wound closure and local infection control. Advancements in technology and therapies hold promise for improving the outcomes for burn injury patients. Understanding the underlying mechanisms of wound repair and tissue regeneration may provide new insights for developing more effective treatments in the future.

Split-level folding, step-type tension-relieving suture technique, and the evaluation on scar minimization.

BACKGROUND: Prevailing tension-reducing suture methods have a spectrum of issues. This study presents a straightforward yet highly efficacious suture technique known as the Split-level Folding, Step-type Tension-relieving Suture technique, which could play a pivotal role in preempting incisional scarring. AIMS: To introduce Split-level Folding, Step-type Tension-relieving Suture technique and assess its effect on scar minimization. METHODS: A retrospective analysis of 64 patients who underwent treatment utilizing the proposed suturing methodology. Assessment parameters included the Patient and Observer Scar Assessment Scale (POSAS), the Vancouver Scar Scale (VSS), scar width, complications, and all evaluated at 6- and 12-month postoperatively. RESULTS: At 12-month follow-up, the POSAS and VSS scores in the normal suture group (32.58 ± 5.43, 3.58 ± 1.39) were considerably higher than the step-type suture group (29.75 ± 3.56, p = 0.0007; 2.78 ± 1.17, p = 0.0006). Moreover, the step-type suture group showcased a significantly narrower average incision scar width (1.62 ± 0.36) than the normal suture group (1.87 ± 0.42, p = 0.0004). This novel tension-relieving suture technique that effectively circumvents the occurrence of persistent localized eversion and other complications often associated with traditional tension-relieving sutures. CONCLUSIONS: The Split-level Folding, Step-type Tension-relieving Suture technique emerges as a highly promising option for averting incisional scarring. This suture method works well for incisions on the chest, back, and extremities, resulting in significantly better long-term outcomes.