Correlation between inflammatory factors, autophagy protein levels, and infection in granulation tissue of diabetic foot ulcer.

OBJECTIVE: To observe the expression of inflammatory factors and autophagy-related proteins in granulation tissue of diabetic foot ulcer (DFU) patients and analyze their relationship with infection. METHODS: This is a retrospective cohort study. One hundred and fifty-two patients with DFU in our hospital from July 2020 to March 2022 were selected as the DFU group, including 98 cases in infection stage group and 54 cases in infection control group. The patients were further graded as the mild (51 cases), the moderate (65 cases), and the severe infection group (36 cases) according to the Wagner grading criteria. Sixty-seven patients with foot burns during the same period were selected as the control group. The distribution of pathogenic bacteria on the ulcer surface was examined using fully automated bacterial analyzer. The expression of inflammatory factors (procalcitonin [PCT], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) was valued by real-time fluorescence quantitative PCR (qRT-PCR). Protein expression was measured by immunohistochemistry (IHC). The correlation was analyzed by Pearson. RESULTS: The surface infection of DFU patients was mostly induced by gram-negative and gram-positive bacteria, with Pseudomonas aeruginosa predominating among the Gram-negative bacteria and Staphylococcus aureus among the gram-positive bacteria. The infection stage group had higher content of PCT, TNF-α, and IL-6 and lower content of Beclin-1 and LC3 than the infection control group (p < .001). The levels of PCT, TNF-α, and IL-6 in the DFU patients with cardiovascular events were higher than those in the nonoccurrence group (p < .001). Glycated hemoglobin in patients with DFU was positively correlated with PCT, TNF-α, and IL-6 levels (p < .05), and negatively correlated with Beclin-1 and LC3 levels (p < .001). CONCLUSION: P. aeruginosa and S. aureus were predominant bacterial in DFU infections. Inflammatory factor and autophagy protein expression were closely correlated with the degree of infection.

Airway necrosis and granulation tissue formation caused by Rhizopus oryzae leading to severe upper airway obstruction: a case report.

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host's immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.

External beam radiotherapy inhibits stent related granulation hyperplasia in rabbit trachea.

Endobronchial stent exacerbates the formation of granulation tissue. Radiotherapy maybe a durable treatment option for granulation hyperplasia. In this study, we explore the results of external beam radiotherapy (EBRT) for granulation hyperplasia after airway stent placement. A total of 30 New Zealand rabbits were assigned in three groups, Control group (n = 12), low dosage (LD, 12 Gy in 4 fractions and twice a week) group (n = 9) and high dosage (HD, 20 Gy in 4 fractions and twice a week) group (n = 9). Post-stenting 1 week, LD and HD group started to receive EBRT. Bronchoscopy, Haematoxylin-eosin (HE), Masson's trichrome (MTS), Safranin O (SO) and immunohistochemical (IHC) staining protocols were performed to evaluate the histopathological changes of trachea. A total of 30 stents were successfully implanted in 30 rabbits. No procedure-related death and complications happened. Post-stenting 4 w, 8 w and 12 w, the ventilate area ratio (VAR) and qualitative histological scoring (QHS) in the LD group and HD group lower than the Control group. Post-stenting 12w, the immunohistochemical results revealed that the positive percentage of TGF-ß and VEGF in the LD group and HD group were lower than the Control group. In conclusion, the present study investigated the efficacy of EBRT in reducing stent related granulation tissue formation in the rabbit trachea. Higher dosage EBRT with a better result in inhibiting granulation hyperplasia.

Amorphous silicate technology produces good results in equine distal limb wound healing.

OBJECTIVE: The objective of this study was to report clinical outcomes of horses with naturally occurring full-thickness skin lacerations treated with an amorphous silicate dressing. We hypothesized that wounds treated with an amorphous silicate dressing would have minimal complications and lesion resolution without formation of exuberant granulation tissue. ANIMALS: 11 client-owned horses. PROCEDURES: Clinical records of 11 horses with distal limb wounds treated with an amorphous silicate dressing were collected from participating veterinarians across the US. Wound healing progression was monitored by the veterinarian and owners. RESULTS: None of the wounds required granulation bed debridement following treatment with topical amorphous silicate dressing. There were no complications associated with the treatment. The size of wounds varied from 5 to 20 cm in length with a median of 10 cm and from 2 to 15 cm in width with a median of 5 cm. Time to resolution varied greatly from 14 to 126 days with a median of 49 days. There was a moderate positive correlation between healing time (days) and area of the wound. All referring veterinarians and owners were satisfied with the healing of the wounds treated with the amorphous silicate dressing. CLINICAL RELEVANCE: Treatment of equine distal limb wounds with an amorphous silicate dressing may reduce development of exuberant granulation tissue and the need for surgical debridement.

Granulation tissue-type hemangioma of ureter: a highly misdiagnosed disease (a rare case report and literature review).

BACKGROUND: Ureteral granulation tissue hemangiomas are rare benign vascular lesions, and they may be clinically asymptomatic or present with massive or recurrent hematuria. Sometimes hemangiomas are difficult to distinguish from malignant ureteral tumors, and most ureteral hemangiomas are confirmed by postoperative pathological examination. This article aims to present a case of granulation tissue-type hemangioma of the ureter and briefly review the current literature on this condition. CASE PRESENTATION: A 30-year-old male patient presented with complaints of painless macroscopic hematuria for 2 months. Computerized tomography of the urinary system showed that the upper 1/3 of the right ureter was occupied, and then the possibility of tumor lesions was considered. The urine cytology showed occasional nuclear abnormalities and many light-stained crystals in urine. Because of suspicious radiological and cytological findings, the patient underwent the right ureteroscopy and the laparoscopic right ureteral mass resection. The postoperative pathological report showed that it was a mesenchymal tumor. The morphological and immunohistochemical staining was consistent with that of hemangioma, tending to granulation tissue hemangioma. After surgery, the patient was in a good state and recovered well at the last follow-up. CONCLUSIONS: Ureteral granulation tissue hemangiomas are an easily misdiagnosed disease. Intermittent painless hematuria is an important characteristic of this disease. Therefore, we suggest that unnecessary radical surgery can be avoided when clinicians consider the possibility of benign ureteral tumors during the evaluation.

Clinical application of PEAK PlasmaBlade to remove distal tracheal granulation in patients after tracheostomy.

OBJECTIVE: Tracheal granulation is one of the common long term complications in patients after tracheostomy. Hypertrophic tracheal granulation may cause airway obstruction and further operation may be required to recreate an airway. Distal tracheal granulation is clinically challenging because of its position and surgical field limitation. This retrospective case review study evaluated the outcomes of PEAK PlasmaBlade-assisted tracheal surgery in patients with distal tracheal granulation. METHODS: This study retrospectively reviewed patients with distal tracheal granulation following long-term tracheostomy. All patients received PEAK PlasmaBlade assistance tracheal surgery (PATS) between February 2013 and December 2019. The surgery was performed using the PEAK PlasmaBlade with TnA type tip, powered by a PULSAR Generator, and guided by a 45 ° rigid endoscope. Patients were regularly followed up for a minimum of 12 months. RESULTS: A total 21 patients had completed PATS. None of the patients experience immediate life-threatening complications during or after the procedure. All the 21 patients were free of recurrent obstructive granulation within 12 months after operation. CONCLUSION: PATS is practical, effective, and safe for distal tracheal granulation and can be performed by single surgeon. Furthermore, it is technically less demanding than other surgical approaches and it has a rapid learning curve.

Study on the Effect and Mechanism of Antibacterial Adhesive Hydrogel on Wound Healing.

Bleeding and infection can cause significant increases in mortalities. Hydrogel sealants have attracted extensive attention for their ability to control bleeding. In this study, the adjuvant treatment with antibacterial adhesive hydrogel dressings was applied to patients with deep second-degree burns/scalds. The traditional medical dressing was regarded as control adjuvant treatment. The results indicated that the total positive rate of bacteria in wound secretions and the pain during dressing change in patients who used antibacterial adhesive hydrogel dressings were significantly reduced. The number of fibroblasts and new capillaries in the granulation tissue of the wound increased, and the patient's wound healing is accelerated. The overall clinical effectiveness has been significantly improved. It is proven that the antibacterial adhesive hydrogel dressing has a significant effect on wound healing.

Insulin Topical Application for Wound Healing in Nondiabetic Patients.

BACKGROUND: Low-cost and safe strategies to improve wound healing will be of great social and economic value. The goal of this pilot clinical trial is aimed at analyzing how effective insulin therapy is at healing wounds in nondiabetic people. METHODS: In this protocol research, 346 individuals were included. Patients were divided as 2 groups at random: experimental patients were given a ten-unit answer. For each 10 cm2 of wound, insulin was injected in solution with 1 mL 0.9 percent saline, whereas the control group got a standard dressing with normal saline. RESULTS: During the therapy period, no adverse effects were reported. After insulin therapy, no substantial insulin-related side effects were reduced. After 10 days of therapy, the experimental group's granulation tissue coverage rate and thickness were considerably improved as compared to control. Furthermore, a momentous difference in the occurrence of wound bleeding and suppurative wounds between the two groups (P = 0.05). CONCLUSION: The results of this pilot research suggest that insulin injections could harmless and effective alternative therapy for wound healing in nondiabetic individuals and that larger, placebo-controlled trials are needed to evaluate effectiveness and safety of insulin treatment in wound healing patients.

The effects of the molecular weight of chitosan on the tissue inflammatory response.

The molecular weight of chitosan (CS) may affect its physical properties and its ability to induce an appropriate host response. The biocompatibilities of CS membranes of low (LMWCS) and high (HMWCS) molecular weight were investigated by inserting these materials into the subcutaneous tissue of rats for 1-28 days and evaluating leukocyte infiltration, granulation tissue, fibrosis, arginase-1 immunostaining, as well as nuclear factor-κB (NF-κΒ) and fibroblast growth factor (FGF)-2 expressions. Both CS membranes induced a peak of leukocyte infiltration on the first day of insertion and stimulated granulation and fibrous tissue generation when compared to control. LMWCS induced more collagen deposition a week earlier, when compared to the control and HMWCS membrane. The membranes also increased arginase-1 immunostaining, a M2 macrophage marker. M2 macrophage is recognized as anti-inflammatory and pro-regenerative. NF-κB is an essential biomarker of the inflammatory process and induces the expression of several pro-inflammatory cytokines. The LMWCS membrane reduced inflammation, as indicated by a reduced nucleus/cytoplasm NF-κB ratio in surrounding tissue from days 7 to 14 when compared to control. On the first day, the expression of FGF-2, a biomarker of inflammatory resolution, was increased in the tissue of the LWMCS group, when compared with HMWCS, which was consistent with the type I collagen deposition. Thus, LWMCS was associated with a prior reduction of the inflammatory response and improved wound healing.

Photothermal therapy via a gold nanoparticle-coated stent for treating stent-induced granulation tissue formation in the rat esophagus.

Minimally invasive therapies using stent technology are currently limited by stent-induced granulation tissue formation adjacent to the stent. The effectiveness of photothermal therapy (PTT) using a gold nanoparticle (AuNP)-coated stent for treating stent-induced granulation tissue formation in the rat esophagus was investigated. All experiments were approved by the animal research committee of our institution. An AuNP-coated, self-expandable metallic stent (SEMS) was produced to conduct PTT under near-infrared laser irradiation. Forty rats were randomly divided into four groups (10 rats each). The animals in group A (non-coated SEMS) and group B (AuNP-coated SEMS with local heating at 65 °C at 4 weeks) were sacrificed 4 weeks after stent placement. The rats in group C (AuNP-coated SEMS with local heating at 65 °C at 4 weeks) and group D (AuNP-coated SEMS with local heating at 65 °C at 4 and 8 weeks) were sacrificed 8 weeks after stent placement. The effectiveness of local heating was assessed by histopathology. All procedures were successful in all of the animals. Seven rats were excluded because of stent migration (n = 2) and death (n = 5). Granulation tissue formation-related variables were significantly higher in group A than in groups B-D (all p < 0.05). Heat-shock protein 70 (HSP70) and TUNEL expression were significantly lower in group A than in groups B-D (all p < 0.05). Granulation tissue formation-related variables were significantly higher in group C than in groups B and D (all p < 0.05). PTT using AuNP-coated SEMS successfully treated granulation tissue formation after stent placement in the rat esophagus.

PRDX4 Improved Aging-Related Delayed Wound Healing in Mice.

Aging-related delayed wound healing is an issue of concern worldwide. Oxidative stress is involved in wound healing. Antioxidative enzymes have various roles in this process. PRDX4, a member of the PRDX family, is upregulated after injury. To investigate the effects of PRDX4 on aging-related wound healing, we subjected C57BL/6J (wild-type), human Prdx4‒transgenic (i.e., hPrdx4+/+), Prdx4-knockout (i.e., Prdx4-/y) mice of three age groups (young, adult, and aged) to skin wound formation. The overexpression of PRDX4 accelerated wound healing in adult and aged mice but not in young mice. Aged hPrdx4+/+ mice showed reduced oxidative stress and inflammation, lower numbers of neutrophils, increased macrophage infiltration, increased angiogenesis, and increased GF levels. The granulation tissue of adult and aged hPrdx4+/+ mice was richer in fibroblasts than that in the matched wild-type mice. PRDX4 deficiency was associated with mortality in adult and aged mice. In vitro, the overexpression of PRDX4 promoted the proliferation and migration of fibroblasts derived from adult or aged mice and made fibroblasts more resistant to the cytotoxicity of hydrogen peroxide. PRDX4 is essential for wound healing and can improve the healing process from multiple aspects, suggesting that it may be very beneficial to wound treatment, especially for the elderly.

Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects.

There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy.

Therapeutic effect of local photothermal heating of gold nanoparticle-coated self-expandable metallic stents for suppressing granulation tissue formation in the mouse colon.

PURPOSE: To investigate the therapeutic effect of local photothermal (PT) heating on suppression of stent-induced granulation tissue formation in mouse colon. MATERIALS AND METHODS: A gold nanoparticle (GNP)-coated self-expandable metallic stent (SEMS) was prepared using a two-step synthesis process for local PT heating under near-infrared laser irradiation. Twenty-four mice were randomly divided into two groups of 12 and subjected to SEMS placement in the colon. Group A received a GNP-coated SEMS without local heating and Group B received a GNP-coated SEMS and underwent local heating at 55°C after SEMS placement. The therapeutic effect of local heating was assessed by comparing the histopathological, immunohistochemical, and endoscopic results. RESULTS: Four mice were excluded because of stent migration (n = 3, group B) or death (n = 1, group A). Stent-induced granulation tissue-related variables were significantly lower in group B than in group A (p < 0.001). In vivo endoscopic images, 4 weeks after stent placement, showed granulation tissue formation over the wire mesh in group A and relatively good patency of the stented colon with no definite irregularities in group B. There was more vascular endothelial growth factor (VEGF) positivity in group A than in group B. CONCLUSION: Local PT heating suppresses granulation tissue formation after stent placement in mouse colon.

Middle-ear or mastoid granulation pathology associated with retraction of the pars flaccida and low-pitched tinnitus.

OBJECTIVE: This study aimed to evaluate the clinical features and outcomes of patients with middle-ear granulation pathologies associated with attic retractions. METHOD: The clinical records of adult patients with middle-ear granulation pathologies and attic retractions confirmed via computed tomography and surgical exploration between January 2012 and January 2019 were retrospectively reviewed. RESULTS: A total of 59 patients were included. Endoscopic examination showed a normal pars tensa but retraction of the pars flaccida in all patients. No granulation tissue or debris were observed. Low-pitched tinnitus was the principal complaint of 55 patients (100 per cent), followed by ear fullness (14 patients, 23.7 per cent). Of the 59 patients, 52 patients (88.1 per cent) underwent canal wall up mastoidectomy and 7 patients (11.9 per cent) underwent endoscopic endaural atticoantrotomy. No ossicular chain destruction was evident. All patients were followed up for 12 months. Tinnitus disappeared completely in 48 patients (81.4 per cent), improved significantly in 9 patients (15.3 per cent) and improved mildly in 2 patients (3.3 per cent). CONCLUSION: A granulation tissue pathology should be considered when a patient complains of low-pitched tinnitus and exhibits retraction of the pars flaccida. Computed tomography and surgical exploration should be scheduled.

Morphological and Histological Changes in the Human Anterior Cruciate Ligament after Rupture.

BACKGROUND: Injuries to the anterior cruciate ligament (ACL) are common and complete tears often fail to heal. ACL reconstruction is considered the surgical gold standard of care for ACL injuries in young active patients. OBJECTIVES: To determine the corresponding morphological and histological features of the torn ACL in different time periods after injury. METHODS: The study included 28 remnant specimens of torn ACLs from patients who had ACL reconstruction surgery of the knee. The remnant pathology was evaluated by its morphology during arthroscopy and by histopathologic measurements. RESULTS: At surgery there were three progressive and distinct morphological tear patterns. The first pattern was noticed within the first 3 months from injury and showed no scar tissue. The second pattern appeared later and was characterized by the appearance of scar tissue with adhesion to the femoral wall. The third pattern was characterized by adhesion of the ACL remnant to the posterior cruciate ligament. The histological changes of the first morphological pattern showed abundance of blood vessels and lymphocytes at the torn femoral end with few irregular collagen fibers. The second and third tear patterns showed decrement in the number of blood vessels and lymphocytes with longitudinally oriented collagen fibers. CONCLUSIONS: The morphological features of the ACL remnant in the first 3 months after injury showed no scar tissue and its histological features had the characteristics of a reparative phase. This phase was followed by a prolonged remodeling phase that ended with attachment of the remnant to the posterior cruciate ligament.

Time- and Dose-Dependent Effects of Pulsed Ultrasound on Dermal Repair in Diabetic Mice.

Chronic wounds, including diabetic, leg and pressure ulcers, impose a significant health care burden worldwide. Some evidence indicates that ultrasound can enhance soft tissue repair. However, therapeutic responses vary among individuals, thereby limiting clinical translation. Here, effects of pulsed ultrasound on dermal wound healing were assessed using a murine model of chronic, diabetic wounds. An ultrasound exposure system was developed to provide daily ultrasound exposures to full-thickness, excisional wounds in genetically diabetic mice. Wounds were exposed to 1 MHz ultrasound (2 ms pulse, 100 Hz pulse repetition frequency, 0-0.4 MPa) for 2 or 3 wk. Granulation tissue thickness and wound re-epithelialization increased as a function of increasing ultrasound pressure amplitude. At 2 wk after injury, significant increases in granulation tissue thickness and epithelial ingrowth were observed in response to 1 MHz pulsed ultrasound at 0.4 MPa. Wounds exposed to 0.4 MPa ultrasound for 3 wk were characterized by collagen-dense, revascularized granulation tissue with a fully restored, mature epithelium. Of note, only half of wounds exposed to 0.4 MPa ultrasound showed significant granulation tissue deposition after 2 wk of treatment. Thus, the db+/db+ mouse model may help to identify biological variables that influence individual responses to pulsed ultrasound and accelerate clinical translation.

Scanning Electron Microscopy in the Evaluation of Defects to the Ossicular Chain in the Course of Chronic Otitis Media.

OBJECTIVE: Chronic otitis media is a heterogeneous disorder. Chronic suppurative otitis media with cholesteatoma and, to a lesser extent, chronic otitis media with granulation lead to the destruction of bone structures within the middle ear. Bone loss may appear in the prominence of the horizontal semicircular canals and the bony canal of the facial nerve. The inflammatory process may spread to the bony labyrinth of the sigmoidal sinuses and the cranial cavities. MATERIALS AND METHODS: The analysis comprised the examination of fragments of auditory ossicles removed during surgery in 21 patients with various types of chronic inflammation of the middle ear. The purpose of this study was to evaluate the usefulness of scanning electron microscopy in evaluating the erosion of middle ear ossicles in different types of chronic otitis media. Images captured at various magnifications were used for the best possible illustration of the observed lesions in bone tissue. RESULTS: The observed lesions and the degree of bone surface damage were dependent on the type of chronic inflammation of the middle ear. The largest destructive changes in the ossicular chain were observed in chronic otitis media with cholesteatoma; smaller changes were observed in chronic otitis media with granulation. CONCLUSION: In the case of damage to the ossicles inflicted by inflammation, the use of a modeled bone block made of a temporal bone taken from outside the tympanic cavity or a biomaterial prosthesis is a good choice in ossiculoplasty.

Patterns of Bone Damage in Patients With Chronic Middle Ear Inflammation.

BACKGROUND: Despite different etiologies, chronic otitis media involves the damaging and restructuring of bone tissue. The inflammatory process destroys elements of the ossicular chain, and bone lesions may appear that allow the development of otogenous complications. AIMS/OBJECTIVES: A correlation between the degree of damage to the ossicular chain as well as the bony walls of the middle ear and the type of chronic inflammatory lesions was sought. Destructive changes to bones were observed using scanning microscopy. MATERIAL AND METHODS: The removed damaged fragments of the ossicles were prepared for evaluation with a scanning microscope. Preparations were sputter-coated with a thin layer of gold and subsequently evaluated. RESULTS: Of 220 surgeries carried out in the discussed period, destruction of the middle ear bone walls, opening the way for the development of intracranial complications, was found in 27 patients. Most of them had ongoing chronic otitis media with granulation. CONCLUSIONS: (1) Bone loss of the skull base was observed more frequently in patients with chronic otitis media with granulation than with cholesteatoma. (2) In chronic otitis media with cholesteatoma, damage to the ossicular chain was observed significantly more frequently than in the case of otitis media with granulation.

Polymeric Composite Dressings Containing Calcium-Releasing Nanoparticles Accelerate Wound Healing in Diabetic Mice.

Objective: Wound healing is a complex process that involves the interaction between different cell types and bioactive factors. Impaired wound healing is characterized by a loss in synchronization of these interactions, resulting in nonhealing chronic wounds. Chronic wounds are a socioeconomic burden, one of the most prominent clinical manifestations of diabetes, however, they lack satisfactory treatment options. The objective of this study was to develop polymeric composites that deliver ions having wound healing properties and evaluate its performance using a pressure ulcer model in diabetic mice. Approach: To develop a polymeric composite wound dressing containing ion-releasing nanoparticles for chronic wound healing. This composite was chemically and physically characterized and evaluated using a pressure ulcer wound model in diabetic (db/db) mice to explore their potential as novel wound dressing. Results: This dressing exhibits a controlled ion release and a good in vitro bioactivity. The polymeric composite dressing treatment stimulates angiogenesis, collagen synthesis, granulation tissue formation, and accelerates wound closure of ischemic wounds created in diabetic mice. In addition, the performance of the newly designed composite is remarkably better than a commercially available dressing frequently used for the treatment of low-exuding chronic wounds. Innovation: The developed nanoplatforms are cell- and growth factor free and control the host microenvironment resulting in enhanced wound healing. These nanoplatforms are available by cost-effective synthesis with a defined composition, offering an additional advantage in potential clinical application. Conclusion: Based on the obtained results, these polymeric composites offer an optimum approach for chronic wound healing without adding cells or external biological factors.

Cell sheets using human amniotic fluid stem cells reduce tissue fibrosis in murine full-thickness skin wounds.

The use of mesenchymal stem cell sheets is a promising strategy for skin regeneration. The injection of dissociated human amniotic fluid stem cells (hAFSCs) was recently found to accelerate cutaneous wound healing with reduced fibrotic scarring, similar to fetal wound healing. However, the use of hAFSCs in applications of cell sheet technology remains limited. The aim of this study was to determine the in vivo efficacy of in vitro-cultured hAFSC sheets in wound healing. The cell sheets were characterized by immunohistochemistry and RT-qPCR and grafted onto full-thickness wounds in BALB/c mice. The wound size was measured, and re-epithelialization, granulation tissue area, and collagen content of the regenerated wound were analyzed histologically. Although the hAFSC sheet contained abundant extracellular matrix molecules and expressed high levels of anti-fibrotic mediators, its grafting did not affect wound closure or the size of the granulation tissue area. In contrast, the organization of type I collagen bundles in the regenerated wound was markedly reduced, while the levels of type III collagen were increased after implantation of the hAFSC sheet. These results suggest that hAFSC sheets can exert anti-fibrotic properties without delaying wound closure.