Complete Re-epithelialization Research Articles

802 A retrospective study: rapid removal of biofilm and necrosis with a hygroscopic chemical debriding compound

IntroductionRemoving necrosis and biofilm is an essential step in the treatment of all lesions. A new debriding compound (TDA) uses a hygroscopic mechanism to reach this goal: when in contact with biofilm and necrosis this causes desiccation, with subsequent dissolution of these compounds.MethodsIn a retrospective proof-of-principle study the results of a one-time application of TDA in 54 serious foot and leg lesions, mainly diabetic and venous ulcers, were analyzed.ResultsOutcomes were positive: at study end: 50 out of 54 lesions (92.5%) showed complete granulation and in 40 out of 54 lesions (74.0%) complete reepithelialization was reached.TDA efficacy is represented by three cases. In the first one, an 83-year-old diabetic female with sever peripheral arterial disease and status post-toes-amputation suffered from a gangrenous lesion of the left foot. A second case involved a 77-year-old female who had a non-healing, post-trauma lesion over the Achilles tendon, and the last case entails an 81-year-old male with a non-healing lesion on the left lower leg. All patients showed very rapid debridement and subsequent healing and reepithelializationConclusionsTypically, diabetic, and venous ulcers require repeated debridement and treatment of the biofilm is notoriously difficult. It also takes a long time before the woundbed is healthy enough to start to granulate and, subsequently, epithelialize. The results, obtained in this study, indicate that a one-time application of TDA is highly effective for “jumpstarting” wound healing.

797 Single Stage Application of Autologous Skin Cell Suspension in Deep Partial Thickness Pediatric Facial Burns

IntroductionDeep partial thickness facial burns in the pediatric population present a dilemma. Standard burn treatment includes excision and split thickness sheet grafting for the face or closure which often yield sub-optimal results. Point-of-care system for autologous skin cell suspension (ASCS) can be utilized as a stand alone option for partial thickness burns. We sought to evaluate our early results from the treatment of pediatric deep partial thickness facial burns using ASCS.MethodsThis was a retrospective cohort analysis of pediatric deep partial thickness facial burns treated with early excision and application of ASCS. After assessment by two surgeons, patients underwent tangential excision with either standard surgical burn knives or dermabrasion. Depth was assessed and if dermal elements were present, then ASCS was applied. Primary outcome was time to >95% reepithelialization, and secondary outcomes were aesthetics, Vancouver Scar Scale, postoperative complications, number of reoperations for wound closure, and need for burn reconstruction.ResultsFrom September 2020 to July 2021, eight pediatric patients (six male and two female) with deep partial thickness facial burns were treated within one week of injury with excision and ASCS. TBSA ranged from 0.3%-24% with some having additional anatomic areas. The mean age was 2.5 years old, with a range of 1.08-5.0 years old. Burn mechanisms included flame, scald, and contact. The mean time from burn injury to initial excision and ASCS was 4.3 days, with a range of 2-7 days. Average time to complete reepithelialization was 20.3 days, with a range of 4-47 days. Average follow up duration was 218 days with a range of 98-365 days. No patients experienced complete graft loss or infection. One patient required need for reoperation with reapplication of polylactic acid skin substitute placed to a small area on the face during closure for other non-face burns. Of the 8 patients, the two patients with the longest times to complete reepithelialization required laser therapy, of which one patient also needed limited facial scar contracture release.ConclusionsEarly, single-staged ASCS application results in good aesthetic and relatively quick healing times with no complications and limited need for additional burn reconstruction. While the results are promising, there is a need for larger studies with longer term follow up before wider applicability.

Therapeutic potential of second degree's skin burns by topical dressing of Teucrium ramosissimum that promotes re-epithelialization.

The aim of the report is to assess the protective effect of powder aerial part of Teucrium ramosissimum (TS) on the in vivo wound-healing of second-degree burn injuries. Teucrium phytocompounds were characterized by FTIR, HPLC, and GC/MS spectra. Burn wound models were employed to evaluate the in vivo wound-healing activity. Thirty six wistar rats with burn wounds were divided into six groups and treated daily with TS, the mixture of Teucrium and honey (TS-HY), thymol and Dermosalic® (0.05%) (DS) creams. Skin epithelialization was monitored on the 4th, 13th, and 21st days. Proteins and the level of malondialdehyde in the burned skin were assessed. Microscopic and macroscopic investigations of skin wound tissues showed significant wound closure rate via complete epidermal reepithelization and regeneration, higher protein content, collagen synthesis and deposition, hair follicles growth post wounding that were promoted in TS-, thymol-, TS-HY- and DS-treated wound tissues compared to the untreated burned wound tissues that was characterized by the absence of the epithelialization, vascularization and the formation of the epidermis layer. Additionally, the skin healing potential of TS and TS-HY was validated by markedly decreased of lipid peroxidation. Overall, TS was found to possess complete wound closure and improves the healing process.

Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome.

Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome.

Effect of “Murcchana samskara” on therapeutic efficacy of BhallatakadiGhrita

‘Bhallatakadi Ghrita’ (BG), comprising the plant extracts of Semecarpus anacardium L., Argemone mexicana L., Cocculus hirsutus L., and Woodfordia fruticosa K. ‘Murcchana samskara’ of ghee before any ‘ghrita-paka’ preparation evidenced the maximum acceptability for topical application. The current study dealt with the effect of the ‘Murcchana’ process on the therapeutic efficacy of BG. In the first step, ‘Murcchita’ ghee was prepared as per reference texts and then developed the ‘Murcchita Bhallatakadi Ghrita’ (M-BG), which was further assessed for wound healing activity using incision and excision wound animal models. ‘Murcchanasamskara’ altered the wound healing ability of M-BG (100% wound contraction on 15th post wounding day with 13.50 ± 0.22 days complete re-epithelization time and 562.33 ± 7.37 g breaking strength). The presence of antioxidants, polyphenols, flavonoids, and fatty acids (known for their potential wound healing properties) in M-BG could accelerate the wound contraction rate (P < 0.001). The present investigation has corroborated the Ayurvedic/traditional attribute of ‘Murcchanasamskara’ to augment the medicinal properties of the BG.

Topical timolol enhances surgical wound healing in the lower portion of the leg in older patients with comorbidities: A retrospective review

Topical timolol enhances surgical wound healing in the lower portion of the leg in older patients with comorbidities: A retrospective review

Comparison of transepithelial and conventional photorefractive keratectomy in myopic and myopic astigmatism patients: a randomized contralateral trial

BackgroundTo assess transepithelial photorefractive keratectomy (tPRK) in terms of corneal epithelial healing rate, postoperative pain, postoperative discomfort, and visual and refraction outcomes compared to mechanical epithelial debridement PRK (mPRK) and alcohol-assisted PRK (aaPRK).MethodsIn this double-masked, randomized clinical trial, thirty-nine patients underwent tPRK in one eye and mPRK in the fellow eye (arm A), and 33 patients underwent tPRK in one eye and aaPRK in the contralateral eye (arm B). All surgical procedures were done using the Schwind Amaris excimer laser. The area of corneal epithelial defect in all eyes was captured and analyzed using ImageJ software.ResultsMean epithelial healing time was respectively 3.74 ± 0.82 and 3.59 ± 0.79 days in tPRK versus mPRK (P = 0.21) in arm A, and 3.67 ± 0.92 and 3.67 ± 0.74 days in tPRK versus aaPRK (P = 1.00) in arm B. Accounting for the initial corneal epithelial defect area, the epithelial healing rate was faster in conventional PRK groups compared to tPRK (both P<0.001) in both arms. However, there was no significant difference in safety, efficacy, spherical equivalent refractive accuracy, or corneal haze development between tPRK and conventional PRK groups (all P > 0.05).ConclusionsAll three methods are effective in terms of visual and refractive outcomes. However, although time to complete re-epithelialization was similar with the three methods, the epithelial healing rate was faster in conventional PRK considering the initial corneal epithelial defect area, and the patients experienced less pain and discomfort in the first postoperative day.Trial registrationIRCT, IRCT20200317046804N1. Retrospectively registered 5 May 2020.

Comparison of heparin dressing and conventional dressing in second degree burn patients in term of pain relief and wound healing.

Objective: To compare effectiveness of heparin soaked and conventional dressing in Second degree burn patients. Study Design: Randomized Controlled study. Setting: Department of Burn and Plastic Surgery, Teaching Hospital/DG Khan Medical College. Period: November 2019 to October 2020. Methodology: One hundred twenty patients fulfilling inclusion criteria were enrolled and randomly divided into two groups. Group A (60 patients) were treated with Heparin soaked Dressing and Group B (60 patients) with conventional dressing (Silver Sulphadiazine ointment 1%) and were observed up to 3-weeks of post treatment. Outcome measures were noted and was assessed by Visual Analogue scale score for pain relief and complete re-epithelization of wound (&gt;75%) in the two groups. Significance was determined by comparing analgesia doses and total days required to heal in each dressing using chi-square test. Results: One hundred twenty patients were selected with mean age of patients was 14.4+_7.4 and male: female (62.5%:37.5%). Mean TBSA% was 12±1.80. Mean pain score in the group A for Superficial partial thickness burn (SPTB) and Deep dermal burn was 4±1 and 6±1 respectively (P-value &lt;0.001). Total Number of days for re-epithelization in the Group A and Group B (SPTB 13±1 vs. 18 measures in term of pain relief and re-epithelization. Total analgesia requirement in the Group A and Group B (50±20 vs. 116±12mg; P-value &lt;0.000 for Superficial Partial Thickness burn and 46±6 vs. 126±12mg; P-value &lt;0.001 for Deep partial thickness burn) respectively. There was significant difference in Outcome. Conclusion: Heparin soaked dressing is more useful and effective in Second degree burn in term of pain relief and re-epithelization in early post burn period compared to the conventional dressing.

3D-MSCs A151 ODN-loaded exosomes are immunomodulatory and reveal a proteomic cargo that sustains wound resolution

IntroductionNon-healing wounds remain a major burden due to the lack of effective treatments. Mesenchymal stem cell-derived exosomes (MSC-Exo) have emerged as therapeutic options given their pro-regenerative and immunomodulatory features. Still, little is known on the exact mechanisms mediated by MSC-Exo. Importantly, modulation of their efficacy through 3D-physiologic cultures together with loading strategies continues underexplored. ObjectivesTo uncover the MSC-Exo-mediated mechanism via proteomic analyses, and to use 3D-culture and loading technologies to expand MSC-Exo efficacy for cutaneous wound healing. MethodsMSC-Exo were produced in either 3D or 2D cultures (Exo3D/Exo2D) and loaded with an exogenous immunosuppressive oligodeoxynucleotide (A151 ODN). Both, loaded and naïve exosomes were characterised regarding size, morphology and the presence of specific protein markers; while IPA analyses enabled to correlate their protein content with the effects observed in vitro and in vivo. The Exo3D/Exo2D regenerative potential was evaluated in vitro by assessing keratinocyte and fibroblast mitogenicity, motogenicity, and cytokine secretion as well as using an in vivo wound splinting model. Accordingly, the modulation of inflammatory and immune responses by A151-loaded Exo3D/Exo2D was also assessed. ResultsExo3D stimulated mitogenically and motogenically keratinocytes and fibroblasts in vitro, with upregulation of IL-1α and VEGF-α or increased secretion of TGF-β, TNF-α and IL-10. In vivo, Exo3D reduced the granulation tissue area and promoted complete re-epithelization of the wound. These observations were sustained by the proteomic profiling of the Exo3D cargo that identified wound healing-related proteins, such as TGF-β, ITGA1-3/5, IL-6, CDC151, S100A10 and Wnt5α. Moreover, when loaded with A151 ODN, Exo3D differentially mediated wound healing-related trophic factors reducing the systemic levels of IL-6 and TNF-α at the late stage of wound healing in vivo. ConclusionOur results support the potential of A151-loaded Exo3D for the treatment of chronic wounds by promoting skin regeneration, while modulating the systemic levels of the pro-inflammatory cytokines.

Multiwalled carbon nanotubes functionalized bacterial cellulose as an efficient healing material for diabetic wounds

The unique pool of features makes bacterial cellulose (BC) a robust platform to tailor its functionalities. Herein, the BC matrix was reinforced with multiwalled carbon nanotubes (MWCNT) to control infection and accelerate the healing process of diabetic wounds. The prepared BC-MWCNT composite film was characterized and antibacterial activity was assessed. Further, the in-vivo wound healing activity was performed and temporal expression of interleukin (IL-1α), tumor necrosis factor (TNF-α), vascular endothelial growth factor (VEGF) and platelets derived growth factor (PDGF) was quantitatively measured by real-time PCR. The characterization results confirmed the reinforcement of the BC matrix with MWCNT. The composite film showed antibacterial activity against all the tested strains. Moreover, the macroscopic analysis of the wound demonstrated faster closure of the diabetic wound in BC-MWCNT group (99% healing) as compared to negative control (77%) in 21 days. Histological studies further supported the results where complete reepithelization of the epidermis and healthy granulation tissue were observed in BC-MWCNT treated group. Molecular studies revealed that BC-MWCNT group showed relatively lesser expression of pro-inflammatory cytokines IL-1α and TNF-α and higher expression of VEGF than control that may have favored the faster healing. This study suggested that the tailorable properties of BC can be exploited to develop composites with potential applications in diabetic wound healing.

Skin wound healing assessment via an optimized wound array model in miniature pigs

An appropriate animal wound model is urgently needed to assess wound dressings, cell therapies, and pharmaceutical agents. Minipig was selected owing to similarities with humans in body size, weight, and physiological status. Different wound sizes (0.07–100 cm2) were created at varying distances but fail to adequately distinguish the efficacy of various interventions. We aimed to resolve potential drawbacks by developing a systematic wound healing system. No significant variations in dorsal wound closure and contraction were observed within the thoracolumbar region between boundaries of both armpits and the paravertebral region above rib tips; therefore, Lanyu pigs appear suitable for constructing a reliable dorsal wound array. Blood flow signals interfered with inter-wound distances ˂ 4 cm; a distance > 4 cm is therefore recommended. Wound sizes ≥ 4 cm × 4 cm allowed optimal differentiation of interventions. Partial- (0.23 cm) and full-thickness (0.6 cm) wounds showed complete re-epithelialization on days 13 and 18 and strongest blood flow signals at days 4 and 11, respectively. Given histological and tensile strength assessments, tissue healing resembling normal skin was observed at least after 6 months. We established some golden standards for minimum wound size and distance between adjacent wounds for effectively differentiating interventions in considering 3R principles.

PACK-CXL vs. antimicrobial therapy for bacterial, fungal, and mixed infectious keratitis: a prospective randomized phase 3 trial

BackgroundInfectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment.MethodsThis is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection.ResultsBetween July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization (P = 0.828) between both treatment groups.ConclusionsPACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin.Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871

Pinhole amniotic membrane for peripheral corneal defects in patients with a single eye or low vision.

To describe the efficacy of a new pinhole amniotic membrane placement technique in cases of peripheral epithelial defects in patients with a single eye or low vision in the contrye. This technique is based on a small central hole done with a dermatological 3 to 4mm punch (according to pupillary diameter in mesoscopic conditions) and a continuous suture in the perilimbal cornea to fix the amniotic membrane. We performed this technique in 6 patients. Patients were followed clinical and photographically. No changes in the visual acuity before and after the surgery were observed. During follow-up, a complete re-epithelialization was observed with no need for reinterventions. Amniotic membrane transplantation is a very useful option in patients with persistent epithelial defects; however, its use is limited by the subsequent visual acuity. The use of the pinhole amniotic membrane technique allows us to treat peripheral persistent corneal lesions without modifying patients' visual acuity. This new technique may become especially useful in patients with functional single eye of low vision in the contralateral eye.

PH-switchable nanozyme cascade catalysis: a strategy for spatial\u2013temporal modulation of pathological wound microenvironment to rescue stalled healing in diabetic ulcer

The management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe3O4-GOx). The Fe3O4-GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial–temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases.Graphical

Injection of Cryopreserved Amniotic Membrane and Umbilical Cord Particulate for Pressure Injuries: A Retrospective Case Series

PI poses a significant burden to society. Cryopreserved AMUC has potential benefits in managing complex wounds owing to its anti-inflammatory, anti-scarring, and proregenerative properties. AMUC grafts are commonly in sheets, but also come as morselized powders that can be sprinkled or injected. The authors initially used AMUC injection in chronic PIs in March 2017. This is a single-center, retrospective review of patients with nonhealing PIs treated with AMUC particulate between March 2017 and November 2018. Incidence of wound healing (zero wound volume with complete reepithelialization) was measured at 12, 24, 36, and 52 weeks. Review included 26 PIs (21 patients); of which, 85% were stage 4 PIs, per the NPIAP staging system. After AMUC injection, 14 PIs (54%) achieved complete wound closure at a median of 12.4 weeks (range, 5-52 weeks). Complete wound closure was observed in 7 patients (27%) at 12 weeks, 10 patients (38%) at 24 weeks, 13 patients (50%) at 36 weeks, and 14 patients (54%) at 52 weeks. One patient with vascular issues required amputation; however, no treatment-related adverse events or complications were observed. These preliminary results suggest that injection of AMUC particulate may be a safe and promising treatment in promoting wound closure of difficult-to-treat PIs.

Effect of honey and propolis, compared to acyclovir, against Herpes Simplex Virus (HSV)-induced lesions: A systematic review and meta-analysis

Ethnopharmacological relevanceApitherapy is a branch of traditional medicine that uses bee products to manage numerous diseases. In this context, the antiherpetic effect of these bee products has been demonstrated in some studies with some controversial results. Aim of the studyThus, we conducted a systematic review and meta-analysis to compare the effectiveness of honey and propolis with acyclovir, the reference drug, in the treatment of cold sores and genital herpes. Materials and methodsThe selection of eligible studies was conducted through the search in Pubmed/MEDLINE, Scopus, Cochrane Library, LILACS, and Electronic Scientific Library. ResultsThe search yielded 147 articles, of which nine were considered eligible for analysis. The analysis of these studies showed that the healing property of propolis is superior to that obtained for acyclovir (95% CI: 2.70 to 8.25; p = 0.0001). Furthermore, honey also presented a better healing effect than acyclovir against Herpes simplex virus-induced wounds (95% CI: 3.58 to −0.19; p = 0.03), inducing complete re-epithelization of herpetic lesions after 8 days, while for acyclovir, the healing time average was 9 days. It also provoked a similar reduction of pain caused by herpetic compared to acyclovir (95% CI: 2.27 to −0.42; p = 0.18). ConclusionsOverall, these results confirm the use of honey and propolis as potent antiherpetic agents.

Possibilities of quadripolar radiofrequency therapy as a method of rehabilitation after surgery for pelvic organ prolapse

Background. This article is devoted to a topical topic in gynecology genital prolapse and methods of preventing recurrence in the postoperative period. Despite the surgery in the field of correction of genital prolapse, up to 13% of patients require repeated surgical treatment of this pathology in the postoperative period.&#x0D; Aim. At present, a unified algorithm for rehabilitation after operations to eliminate this pathology has not yet been developed. We proposed a technique for using quadripolar radiofrequency therapy in patients operated on for pelvic organ prolapse in the postoperative period in order to improve the rehabilitation period.&#x0D; Materials and methods. To achieve our goals, histological material was collected from 60 patients with pelvic organ prolapse before and after surgical treatment to assess the strength of collagenogenesis and reparative processes in the connective tissue of the vagina based on changes in the expression of the RNA matrix of collagen types I and III, genes encoding vascular endothelial growth factor VEGF-A, transforming growth factor TGF-B1 and decorin by polymerase chain reaction. The FSFI-19 questionnaire was used to analyze the quality of the patients' sexual life. We also calculated the vagina health index of patients suffering from this disease.&#x0D; Results. In the course of the study, it was revealed that when using this method, complete re-epithelization of tissues occurs by 90 days after the operation, metabolic and trophic processes in the tissues of the urogenital tract intensify, and an increased degree of patient satisfaction with the quality of sexual life.&#x0D; Conclusion. All the results obtained confirmed the therapeutic effect of radiofrequency therapy in the postoperative period, which makes it possible to use the technique as a rehabilitation program after surgical treatment for genital prolapse.

Controlled pVEGF delivery via a gene-activated matrix comprised of a peptide-modified non-viral vector and a nanofibrous scaffold for skin wound healing

Regulating cell function and tissue formation by combining gene delivery with functional scaffolds to create gene-activated matrices (GAMs) is a promising strategy for tissue engineering. However, fabrication of GAMs with low cytotoxicity, high transfection efficiency, and long-term gene delivery properties remains a challenge. In this study, a non-viral DNA delivery nanocomplex was developed by modifying poly (D, L-lactic-co-glycolic acid)/polyethylenimine (PLGA/PEI) nanoparticles with the cell-penetrating peptide KALA. Subsequently, the nanocomplex carrying plasmid DNA encoding vascular endothelial growth factor (pVEGF) was immobilized onto a polydopamine-coated electrospun alginate nanofibrous scaffold, resulting in a GAM for enhanced skin wound healing. The nanocomplex exhibited much lower cytotoxicity and comparable or even higher transfection efficiency compared with PEI. The GAM enabled sustained gene release and long-tern transgene expression of VEGF in vitro. In an excisional full-thickness skin wound rat model, the GAM could accelerate wound closure, promote complete re-epithelization, reduce inflammatory response, and enhance neovascularization, ultimately enhancing skin wound healing. The current GAM comprising a low-toxic gene delivery nanocomplex and a biocompatible 3D nanofibrous scaffold demonstrates great potential for mediating long-term cell functions and may become a powerful tool for gene delivery in tissue engineering. Statement of significanceGene delivery is a promising strategy in promoting tissue regeneration as an effective alternative to growth factor delivery, but the study on three-dimensional gene-activated scaffolds remains in its infancy. Herein, a biodegradable nanofibrous gene-activated matrix integrating non-viral nanoparticle vector was designed and evaluated both in vitro and in vivo. The results show that the nanoparticle vector provided high transfection efficiency with minimal cytotoxicity. After surface immobilization of the nanocomplexes carrying plasmid DNA encoding vascular endothelial growth factor (pVEGF), the nanofibrous scaffold enabled sustained DNA release and long-term transgene expression in vitro. In a rat full-thickness skin wound model, the scaffold could accelerate wound healing. This innovative gene-activated matrix can be a promising candidate for tissue regeneration.

Modified montmorillonite-bacterial cellulose composites as a novel dressing system for pressure injury

The main objective of this study was to investigate the effects of bacterial cellulose hydrogel (BCH) incorporated into montmorillonite (MMT) and its underlying mechanisms of action on a skin wound healing mouse model following pressure injury model. Komagataeibacter hansenii was used to obtain 5 cm in diameter and 0.8 mm of thickness circular bacterial cellulose (BC) sheets, which were incorporated with MMT by deposition ex-site using a 0.1% MMT suspension (100 rpm for 24 h at 28 °C). Afterward, Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM) were used to characterize the bacterial cellulose hydrogel incorporated into montmorillonite (BCH-MMT). The pressure injury model was assessed by macroscopic and histological analysis in male Swiss mice. Both, BC and BCH-MMT, showed a typical FTIR spectrum of cellulosic substrates with pronounces bands around 3344, 2920, 1637, and 1041 cm−1 while microparticles of MMT dispersed uniformly throughout BC were revealed by SEM photographs. Animals treated with BCH-MMT showed significant healing of pressure ulcers as demonstrated by reduced area of redness and spontaneous hyperalgesia, lower amounts of in-site inflammatory cells (to the same level as the positive control Dersani®) and ultimately, complete epidermis re-epithelialization and tissue regeneration. Altogether, these findings suggest that a modified BCH-MMT film could serve as scaffolding for skin tissue engineering and potentially as a novel dressing material for pressure injury.

Therapeutic effects of equine amniotic membrane suspension on corneal re-epithelialization and haze in amodified lagomorph ex vivo wound healing model.

To investigate the therapeutic effects of topical equine amniotic membrane (eAM) suspension following corneal wounding in a controlled experimental setting. Equine amniotic membrane was collected, gamma irradiated, homogenized for topical suspension preparation, and cryopreserved. Corneoscleral rims harvested from fresh rabbit globes were wounded via keratectomy and were maintained in an air-liquid interface ex vivo corneal culture model. Treatment groups included topical gamma irradiated eAM suspension (n=20) and a control group (n=20). Re-epithelialization of the wound was assessed with daily photographic evaluation of area of fluorescein uptake (mm2 ). Corneal wound haze after a 21-day period was assessed by photographic analysis of haze area (mm2 ) and pixel intensity (0-255). Histologic processing of corneal tissue was performed, and protein identification of eAM suspension using Liquid chromatography-mass spectrometry (LC-MS). The average day of complete corneal re-epithelialization in controls (5.5±1.1) and topically treated (5.5±0.6) corneas, and rates of reduction in area of fluorescein uptake over time did not significantly differ (p=.44). The corneal wound haze was significantly reduced in mean area by approximately 52% and intensity by 57% in corneas treated with topical eAM suspension (p<.05), compared to controls 21days following wounding. Protein analysis identified numerous proteins, specifically decorin, dermatopontin, and lumican, which have previously been documented in eAM. Area and intensity of corneal wound haze were significantly reduced in corneas treated with gamma irradiated eAM suspension, which may be due to previously identified therapeutic proteins which promote corneal clarity.