5-Aminolevulinic Acid-Mediated Photodynamic Therapy Improves Vocal Fold Wound Healing in Rats.

OBJECTIVE: Studies showed that photodynamic therapy (PDT) might be able to prevent vocal fold scar formation when treating laryngeal lesions. We aim to investigate if PDT improves vocal wound healing and reduces scar formation in both prophylactic and remodeling procedures performed in vivo. STUDY DESIGN: In vivo. METHODS: Vocal fold stripping was performed in Sprague-Dawley rats. PDT was performed with intraperitoneal injection of 100 mg/kg 5-Aminolevulinic Acid (5-ALA) and 635 nm laser irradiation of 20, 40, and 60 J/cm2 . PDT was performed immediately after surgery to study the prophylactic effect and 4 weeks after surgery to study the remodeling effect. Gene expression was evaluated with real-time PCR at 1 week after PDT. Histologic evaluations were performed 12 weeks after PDT, including hematoxylin-eosin, Masson, Alcian blue staining, and immunohistochemical staining of collagen I and III. RESULTS: PDT induced similar effects on the vocal fold wound healing outcomes in both prophylactic and remodeling procedures. Expression of MMP8, MMP13, HAS2, and TGFß1 was significantly elevated. Histologic evaluation revealed significantly increased thickness, decreased density of collagen, and increased deposition of hyaluronic acid in the lamina propria. Immunohistochemistry also revealed better distribution and reduced density of collagen I and III. The most obvious changes were seen in the 60 J/cm2 PDT group. CONCLUSION: PDT could significantly improve vocal wound healing by providing both prophylactic effects and remodeling effects. It may be a minimally invasive treatment for vocal fold lesions with slight vocal scarring, and may be used to treat acute or chronic vocal injury to reduce vocal scarring. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:1943-1951, 2023.

Histological Analysis of the Effect of Nanofat Grafting in Scar Rejuvenation.

Introduction: The morphology and tissue response to macro- and micro-fat grafting have been widely studied in both clinical and experimental settings; the histological effects of the nanofat graft, however, remain largely unexplored. Aims: This study was carried out to evaluate the histological changes leading to scar rejuvenation in a fine scar following nanofat grafting. Materials and Methods: This was an experimental study carried out on guinea-pig fine-line scar models. Nanofat prepared from abdominal fat of the animal was injected into scar on right legs (NFG) at 1 month whereas left acted as controls (CG). Punch biopsies from all scars were analyzed at 2, 4, and 6 months by Hematoxylin&Eosin, Masson's trichrome, and Picrosirius red stains to evaluate dermal/epidermal regeneration, collagen fiber orientation, pattern of distribution, and amount of mature and immature collagen. Results: Nine animals were included in the final analysis of the study. On histological analysis, the amount of inflammatory infiltrate, collagen fiber orientation, pattern and total histological score at 2, 4, and 6 months were similar between the groups. There was an increased trend for earlier appearance of organized and mature forms of collagen in the NFG group. The distribution of collagen was similar at 2 months; however, there was a significant increase in collagen distribution in NFG at 4 months (NFG: 46.11±11.6, CG: 31.16±9.9; P = 0.010) and at 6 months (NFG: 63.48± 6.6, CG: 49.9 ±8.8; P = 0.002). Conclusion: Nanofat grafting is associated with an accelerated and increased production of mature collagen with proper alignment in fine-line scars.

High-velocity pneumatic injection of non-crosslinked hyaluronic acid for skin regeneration and scar remodeling: A retrospective analysis of 115 patients.

BACKGROUND: Pneumatic-assisted high velocity jet injections are an alternative method for intradermal delivery of hyaluronic acid (HA) and demonstrated efficacy in dermal thickening and scar remodeling with minimal side effects. AIMS: We aimed to investigate the clinical efficacy comparing non-crosslinked HA (NCL-HA) and crosslinked HA (CL-HA) for aesthetic skin concerns. METHODS: We retrospectively analyzed charts of 115 patients treated with jet injected NCL-HA and CL-HA for skin rejuvenation, age-related laxity and rhytidosis, hypertrophic and acne scars and striae. Global Aesthetic Improvement Scale (GAIS) and the 5-grade patient satisfaction scale were used for assessment of the treatment efficacy at the 3-month follow-up. Efficacy was separately analyzed between patients receiving NCL-HA vs. CL-HA. Longevity of treatment effect was measured by the time to voluntary return for repeat treatment. RESULTS: An average of 2.8 treatments was completed per patient with a low incidence of side effects including bruises (7%) and temporary local edema (1%). Patients were highly-satisfied with the treatment results in all categories with the average satisfaction scores of 3.68 (NCL-HA) and 3.76 (CL-HA). An average GAIS score of 1.7 ("much improved") was calculated for neck, décolleté and perioral areas. An overall GAIS score averaged as 1.78 (NCL-HA) and 1.6 (CL-HA). Longevity of the effect averaged 13.1 months for NCL-HA and 13.2 months for CL-HA groups. CONCLUSION: Our retrospective data showed similar significant improvement of all aesthetic skin concerns in 115 subjects treated with either NCL-HA or CL-HA delivered intradermally by a high velocity jet-injector device with minimal downtime, pain or side-effects.

Effectiveness and safety of 2940-nm multifractional Er: YAG laser on acne scars.

Erbium: Yttrium-aluminum-garnet laser (Er: YAG) treatment has been used in resurfacing the acne scars for a long time; however, we could not find any study reporting the recovery rates after each session of the treatment. In this study, we aimed to report the improvement rates after each session. We retrospectively analyzed the data of 35 patients with acne scars treated with fractional ablative Er: YAG laser. The patients received one to four sessions of treatment with 4-week intervals and improvement rates were recorded after each session. Data are available on request from the authors. The improvement rate of the lesions varied between 1% and 25% in 34 patients at the end of the first session, while in one patient, the improvement rate was detected as 26% to 50%. At the end of the fourth session, the rate of improvement was 26% to 50% in 14 out of 24 patients and 51% to 75% in 10 patients. None of the patients showed a 76% to 100% improvement at the end of the fourth session, whereas 48.6% of the patients were satisfied with the treatment. In patients with a high expectation of an excellent improvement, a higher number of sessions of the laser treatment and/or combination treatments with different treatment methods should be planned.

Fat Grafting for Treatment of Facial Burns and Burn Scars.

This article presents the authors' experience with the use of fat grafting via the Coleman technique, for the adjuvant treatment of facial burn wounds and their sequelae. It demonstrates the regenerative effects of fat injected under the wound and/or the scar as well as of fat delivered to the debrided surface of the wound and to the surface of the scar after laser treatment or microneedling.

Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model.

PURPOSE: Relaxin (RLX) is a transforming growth factor-ß1 (TGF-ß1) antagonist that is believed to function as a potent collagen re-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer gene therapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expression to scar remodeling was assessed using an injectable alginate gel-matrix system. MATERIALS AND METHODS: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas, color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. RESULTS: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-ß1 and upregulated TGF-ß3 mRNAs in pig scar tissues. CONCLUSION: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeutic effects on scar formation.

Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model

PURPOSE: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagen re-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer gene therapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expression to scar remodeling was assessed using an injectable alginate gel-matrix system. MATERIALS AND METHODS: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas, color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. RESULTS: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-β1 and upregulated TGF-β3 mRNAs in pig scar tissues. CONCLUSION: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeutic effects on scar formation.

Quantitative differentiation of normal and scarred tissues using second-harmonic generation microscopy.

The aim of this study was to differentiate normal and scarred hamster cheek pouch samples by applying a quantitative image analysis technique for determining collagen fiber direction and density in second-harmonic generation microscopy images. This paper presents a collagen tissue analysis of scarred cheek pouches of four adult male Golden Syrian hamsters as an animal model for vocal fold scarring. One cheek pouch was scarred using an electrocautery unit and the other cheek was used as a control for each hamster. A home-built upright microscope and a compact ultrafast fiber laser were used to acquire depth resolved epi-collected second-harmonic generation images of collagen fibers. To quantify the average fiber direction and fiber density in each image, we applied two-dimensional Fourier analysis and intensity thresholding at five different locations for each control and scarred tissue sample, respectively. The resultant depth-resolved average fiber direction variance for scarred hamster cheek pouches (0.61 ± 0.03) was significantly lower (p < 0.05) than control tissue (0.73 ± 0.04), indicating increased fiber alignment within the scar. Depth-resolved average voxel density measurements indicated scarred tissues contained greater (p < 0.005) fiber density (0.72 ± 0.09) compared to controls (0.18 ± 0.03). In the present study, image analysis of both fiber alignment and density from depth-resolved second-harmonic generation images in epi-detection mode enabled the quantification of the increased collagen fiber deposition and alignment typically observed in fibrosis. The epi-detection geometry is the only viable method for in vivo imaging as well as imaging thick turbid tissues. These quantitative endpoints, clearly differentiating between control and scarred hamster cheek pouches, provide an objective means to characterize the extent of vocal fold scarring in vivo in preclinical and clinical research. In particular, this non-invasive method offers advantages for monitoring scar treatments in live animals and following the effects of scarring-related treatments such as application of steroids or drugs targeting pathways involved in fibrosis. SCANNING 38:684-693, 2016. © 2016 Wiley Periodicals, Inc.

Fat grafting for treatment of burns, burn scars, and other difficult wounds.

This article presents the authors' 3-year experience with the use of fat grafting, via the Coleman technique, for the adjuvant treatment of burn wounds, venous ulcers, diabetic ulcers, and burn scars. It demonstrates the regenerative effects of fat injected under the scar, and of fat injected under the wound, in the periphery of the wound, and within a bone fracture line or space, and of fat deposited over the wound.