Medial Plantar Artery Perforator Kiss Flap for Salvage of Extensive Palmar Skin Defect.

BACKGROUND: Flaps based on the medial plantar artery (MPA) accomplish favorable surgical outcomes in palmar resurfacing due to its outstanding texture, pliability and contour, but primary closure could not be achieved at the donor site when the flap was designed to be relatively large. In this study, the kiss technique was employed for the reconstruction of extensive palmar defects which minimized donor site morbidity. METHODS: A modified flap surgical strategy was systemically developed based on the perforator distribution of the MPA through our cadaver study. Two or three narrow small skin paddles based on MPA were raised and resembled at the recipient site as a larger flap. S-2PD, hypersensitivity and ROM, QuickDASH, gait and patient satisfaction were evaluated 6 months to 12 months postoperation. RESULTS: From June 2015 to July 2021, 20 cases of reconstruction using the medial plantar artery perforator (MPAP) kiss flap were performed for the resurfacing of palmar skin defects. All flaps survived uneventfully with coverage matching the texture and color of the recipients except one flap that exhibited venous congestion and recovered after revision. 12 flaps (60 percent) were double-paddled and 8 flaps (40%) were triple-paddled with a resurfacing area of 27.19cm 2 and 41.1cm 2 respectively. All donor sites achieved primary closure without major complications. CONCLUSIONS: Versatile kiss flap combinations were developed based on further understanding of the MPA system. Durable and pliable characters of the MPAP flap provide excellent reconstruction for extensive palmar defects while minimizing donor site complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Using Zhang's supertension-relieving suture technique with slowly-absorbable barbed sutures in the management of pathological scars: a multicenter retrospective study.

Background: An ideal tension-relieving suture should be efficient for >3 months to retrieve normal tensile strength. Most preexisting suturing techniques provided tension elimination followed by relapse and scar proliferation due to absorption and cut-through of the sutures. This study introduces a simple but effective suture technique developed by a senior author (ZYX) to solve this problem. Methods: A total of 120 patients with pathological scar (PS) had intervention treatment with the proposed suturing strategy at three centers from January 2018 to January 2021. A slowly absorbable 2-0 barbed suture was used for subcutaneous tension relieving with a set-back from the wound edge and a horizontal interval between proposed inserting points of 1 cm. The Patient and Observer Scar Assessment Scale (POSAS), scar width, perfusion and eversion of the wound edge were evaluated at 3-, 6- and 12-month follow-up. The time needed to place the tension-relieving suture was recorded and relapse was monitored for 18 months postoperatively. Results: In total, 76 trunks, 32 extremities and 12 cervical PS were included, with an average subcutaneous tension-relieving suture time of 5 min. The Patient and Observer Scar Assessment Scale (POSAS) score decreased from 84.70 ± 7.06 preoperatively to 28.83 ± 3.09, 26.14 ± 1.92 and 24.71 ± 2.00 at 3, 6 and 12 months postoperatively, respectively (p < 0.0001). The scar widths were 0.17 ± 0.08, 0.25 ± 0.09 and 0.33 ± 0.10 cm, respectively, with perfusion significantly decreased from 213.64 ± 14.97 to 112.23 ± 8.18 at 6 months (p < 0.0001). The wound edge flattened out during the first 3 months in most cases with only two scar relapses. Conclusions: Zhang's suture technique provides a rapid and long-lasting tension-relieving effect with ideal scar appearances and lower relapse rates in the surgical management of PS.

Effects and Progress of Photo-Crosslinking Hydrogels in Wound Healing Improvement.

Wound healing is a dynamic physiological process, including three stages: inflammation, tissue formation, and remodeling. The quality of wound healing is affected by many topical and systemic factors, while any small factor may affect the process. Therefore, improving the quality of wound healing is a complex and arduous challenge. Photo-crosslinking reaction using visible light irradiation is a novel method for hydrogel preparation. Photo-crosslinking hydrogels can be controlled in time and space, and are not interfered by temperature conditions, which have been widely used in the fields of medicine and engineering. This review aims to summarize the application of photo-crosslinking hydrogels in improving the quality of wound healing, mainly including the material design, application mechanism, and effect of photo-crosslinking hydrogels applied in wound healing, followed by the applicable animal models for experimental research. Finally, this review analyzes the clinical application prospects of photo-crosslinking hydrogels in the field of wound healing.

The Use of Infrared Thermography in Determining Timing for Early Pedicle Division of the Preexpanded Bipedicled Visor Flap after Ischemic Preconditioning.

Background: The preexpanded bipedicled visor flap, supported by the bilateral superficial temporal vessels, stands as an ideal choice for upper and lower lip reconstruction in males. However, the bilateral tissue bridges after flap transfer caused patients significant cosmetic deformity and psychological burden. Early division of bilateral pedicles reduced the length of hospitalization and expenses. In this study, infrared thermography (IRT) was used to guide the early pedicle division after ischemic preconditioning. Methods: This study retrospectively analyzed patients who underwent preexpanded bipedicled visor flap surgery from April 2018 to October 2021. Pedicle division was scheduled at two weeks postflap transfer. Ischemic preconditioning was initiated 3-5 days in advance by repeatedly clamping both pedicles. The temperature alteration of the flap and the temperature difference compared to the normal adjacent tissue were evaluated by IRT. The division surgery was not scheduled until the perfusion assessment indicated adequate. This comprised of subjective examination and indocyanine green angiography. The threshold of temperature difference to determine the pedicle division was analyzed based on the temperature changes between the clamps. Results: A total of 8 male patients successfully conducted the pedicle division without any complications. The delay period after ischemic preconditioning ranged from 14 to 19 days (average 16 days). Through ischemic preconditioning training, the average temperature of the flap gradually increased from 31.85 ± 0.36°C to 33.89 ± 0.50°C, and the temperature difference with the normal surrounding tissues decreased from 2.89 ± 0.30°C to 1.15 ± 0.46°C (95% confidence interval (1.5, 0.8)). The temperature difference stayed unchanged after pedicle division. Conclusion: Ischemic preconditioning shortens the perioperative period to pedicle division. Monitoring the temperature change reflects the revascularization between the flap and the recipient site, thus guiding the pedicle division. The temperature difference less than 1.5°C after clamping both pedicles can be set as the safe threshold for pedicle division.

Microneedle delivery of botulinum toxin type A combined with hyaluronic acid for the synergetic management of multiple sternal keloids with oily skin: A retrospective clinical investigation.

BACKGROUND: For the treatment of sternal keloids, corticosteroid therapy has side effects including abnormal sebum secretion and acne. Relapse of keloids is common after corticosteroid injection in patients with oily skin. To reduce side effects and keloid recurrence, we used a combination of botulinum toxin type A (BTX-A) and hyaluronic acid (HA) as synergetic management for multiple sternal keloids in patients with oily skin. METHODS: In total, 58 patients with multiple sternal keloids who received monthly steroid injections were retrospectively included. Thirty-two patients in the intervention group received an additional injection of BTX-A/HA on the same day as the first injection of the steroid, while the remaining 26 patients were treated as the control group. At baseline and follow-up visits, sebum production and transepidermal water loss (TEWL) were assessed as primary outcomes, and the Vancouver Scar Scale (VSS) score, keloid recurrence, visual analog scale (VAS) score, and patient satisfaction were assessed as secondary outcomes. RESULTS: In the control group, average sebum production and TEWL were increased to 132% and 104% of baseline, respectively, at the 24-week follow-up. In the intervention group, average sebum production and TEWL reached nadir at the 8-week follow-up and then increased to 96% and 91% of baseline, respectively, at the 24-week follow-up. Sternal keloid relapse was observed in 88.5% of the patients in the control group and none of the patients in the intervention group. The total VSS score at 24 weeks was 11.04 ± 0.14 and 8.93 ± 0.26 (p < 0.001) in the control group and intervention group, respectively, and the VAS score was 75 ± 5.10 and 19.14 ± 3.80 (p < 0.001) in the control group and intervention group, respectively. Higher patient satisfaction was reported in the intervention group. CONCLUSIONS: Microneedle delivery of BTX-A/HA decreases sebum production while improving skin barrier function. Thus, this combined therapy can relieve the side effects of corticosteroid therapy and reduce keloid recurrence.

Dramatic Effect of Botulinum Toxin Type A on Hypertrophic Scar: A Promising Therapeutic Drug and Its Mechanism Through the SP-NK1R Pathway in Cutaneous Neurogenic Inflammation.

Background: Hypertrophic scar formation may be related to cutaneous neurogenic inflammation (CNI) through the substance P-neurokinin 1 receptor (SP-NK1R) signaling pathway. As a widely used drug in aesthetic clinical work, botulinum toxin type A (BTX-A) has a therapeutic effect on scars, but the actual mechanism remains unclear. This study aimed to clarify the potential mechanism by which BTX-A inhibits CNI in hypertrophic scars both in vitro and in vivo. Methods: Tissue samples were obtained from surgical excisions. Immunohistological analysis was used to locate SP in human hypertrophic scars and normal skin. RT-PCR and western blot analysis were used to evaluate the expression of collagens after SP/BTX-A treatment. A rabbit ear scar model was used to explore the in vivo effect of BTX-A on scar treatment. Results: SP and NK-1R were overexpressed in hypertrophic scars compared to normal skin tissues. Collagen secretion of hypertrophic scar-derived fibroblasts increased with increasing doses of SP. However, BTX-A may downregulate collagen expression through SP-NK1R pathway with or without the presence of SP inducing agent capsaicin. Meanwhile, SP inhibited the expression of NK-1R, and this inhibition was blocked by pretreatment with BTX-A. In vivo, intralesional BTX-A injection can also reduce the volume of scars and inhibit collagen secretion. Capsaicin may cause more severe scar manifestations, while the therapeutic effect of BTX-A remains. Conclusion: Our research confirms that CNI stimulates fibroblasts during scar formation, while BTX-A can reduce collagen secretion by inhibiting the SP-NK1R signaling pathway, thus identifying a novel therapeutic target for this benign solid skin tumor.

Potential therapeutic effect of NK1R antagonist in diabetic non-healing wound and depression.

Diabetes is a global disease with huge impacts on patients due to its complications, among which non-healing wounds and depression are common and challenging. The neurokinin 1 receptor (NK1R) inhibitor, aprepitant has been broadly applied for an antidepressant effect in depressive patients. Recent literature has indicated a therapeutic effect of downregulation in NK1R to diabetes-related fracture, cardiomyopathy, gastroparesis, and ocular surface disorders. In this study, differential expression genes in diabetes and depression were analyzed based on several RNA sequencing datasets from the GEO database to confirm NK1R in the overlapping set. Interaction network and gene set enrichment analysis were subsequently conducted. As a result, NK1R-related genes took part in angiogenesis, epithelial-mesenchymal transition (EMT), collagen deposition, and inflammation in diabetes and depression. In vivo, the downregulation of NK1R was proved to promote vascular proliferation and enhance diabetic wound healing, which provides a potential therapeutic target for the management of diabetic non-healing wounds and depression.

IR-808 loaded nanoethosomes for aggregation-enhanced synergistic transdermal photodynamic/photothermal treatment of hypertrophic scars.

Synergistic transdermal photodynamic therapy (PDT)/photothermal therapy (PTT) has emerged as a novel strategy for improving hypertrophic scar (HS) therapeutic outcomes. Herein, a near-infrared heptamethine cyanine dye, named IR-808, has been selected as the desirable photosensitizer owing to its PDT and PTT properties. Benefitting from the transdermal delivery ability of ethosomes (ESs), IR-808 loaded nanoethosomes (IR-808-ES) have been prepared as a novel nanophotosensitizer for the transdermal PDT/PTT of HSs. The special structure of IR-808 aggregate distribution in the ES lipid membrane enhances ROS generation and hyperthermia. The in vitro experiments indicate that the IR-808-ES enhances the PDT/PTT efficacy for inducing the HS fibroblast (HSF) apoptosis via the intrinsic mitochondrial pathway. Furthermore, the in vivo transdermal delivery studies reveal that the IR-808-ES efficiently delivers IR-808 into HSFs in the HS tissue. Systematic assessments in the rabbit ear HS models demonstrate that the enhanced PDT/PTT performance of the IR-808-ES has remarkable therapeutic effects on improving the HS appearance, promoting HSF apoptosis and remodeling collagen fibers. Therefore, the IR-808-ES integrates both the transdermal delivery ability and the aggregation-enhanced PDT/PTT effect, and these features endow the IR-808-ES with significant potential as a novel nanophotosensitizer for the transdermal phototherapy of HSs in the clinical field.

Recent Progress in Transdermal Nanocarriers and Their Surface Modifications.

Transdermal drug delivery system (TDDS) is an attractive method for drug delivery with convenient application, less first-pass effect, and fewer systemic side effects. Among all generations of TDDS, transdermal nanocarriers show the greatest clinical potential because of their non-invasive properties and high drug delivery efficiency. However, it is still difficult to design optimal transdermal nanocarriers to overcome the skin barrier, control drug release, and achieve targeting. Hence, surface modification becomes a promising strategy to optimize and functionalize the transdermal nanocarriers with enhanced penetration efficiency, controlled drug release profile, and targeting drug delivery. Therefore, this review summarizes the developed transdermal nanocarriers with their transdermal mechanism, and focuses on the surface modification strategies via their different functions.

Single-Cell and Bulk Transcriptome Data Integration Reveals Dysfunctional Cell Types and Aberrantly Expressed Genes in Hypertrophic Scar.

Hypertrophic scar (HS) is a common skin disorder characterized by excessive extracellular matrix (ECM) deposition. However, it is still unclear how the cellular composition, cell-cell communications, and crucial transcriptionally regulatory network were changed in HS. In the present study, we found that FB-1, which was identified a major type of fibroblast and had the characteristics of myofibroblast, was significantly expanded in HS by integrative analysis of the single-cell and bulk RNA sequencing (RNA-seq) data. Moreover, the proportion of KC-2, which might be a differentiated type of keratinocyte (KC), was reduced in HS. To decipher the intercellular signaling, we conducted the cell-cell communication analysis between the cell types, and found the autocrine signaling of HB-1 through COL1A1/2-CD44 and CD99-CD99 and the intercellular contacts between FB-1/FB-5 and KC-2 through COL1A1/COL1A2/COL6A1/COL6A2-SDC4. Almost all the ligands and receptors involved in the autocrine signaling of HB-1 were upregulated in HS by both scRNA-seq and bulk RNA-seq data. In contrast, the receptor of KC-2, SDC4, which could bind to multiple ligands, was downregulated in HS, suggesting that the reduced proportion of KC-2 and apoptotic phenotype of KC-2 might be associated with the downregulation of SDC4. Furthermore, we also investigated the transcriptionally regulatory network involved in HS formation. The integrative analysis of the scRNA-seq and bulk RNA-seq data identified CREB3L1 and TWIST2 as the critical TFs involved in the myofibroblast of HS. In summary, the integrative analysis of the single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data greatly improved our understanding of the biological characteristics during the HS formation.