Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization. / 纳米银通过调控巨噬细胞极化以减轻异物反应并促进创面修复.

Foreign body reactions induced by macrophages often cause delay or failure of wound healing in the application of tissue engineering scaffolds. This study explores the application of nanosilver (NAg) to reduce foreign body reactions during scaffold transplantation. An NAg hybrid collagen-chitosan scaffold (NAg-CCS) was prepared using the freeze-drying method. The NAg-CCS was implanted on the back of rats to evaluate the effects on foreign body reactions. Skin tissue samples were collected for histological and immunological evaluation at variable intervals. Miniature pigs were used to assess the effects of NAg on skin wound healing. The wounds were photographed, and tissue samples were collected for molecular biological analysis at different time points post-transplantation. NAg-CCS has a porous structure and the results showed that it could release NAg constantly for two weeks. The NAg-CCS group rarely developed a foreign body reaction, while the blank-CCS group showed granulomas or necrosis in the subcutaneous grafting experiment. Both matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were reduced significantly in the NAg-CCS group. The NAg-CCS group had higher interleukin (IL)-10 and lower IL-6 than the blank CCS group. In the wound healing study, M1 macrophage activation and inflammatory-related proteins (inducible nitric oxide synthase (iNOS), IL-6, and interferon-|γ (IFN-|γ)) were inhibited by NAg. In contrast, M2 macrophage activation and proinflammatory proteins (arginase-1, major histocompatibility complex-II (MHC-II), and found in inflammatory zone-1 (FIZZ-1)) were promoted, and this was responsible for suppressing the foreign body responses and accelerating wound healing. In conclusion, dermal scaffolds containing NAg suppressed the foreign body reaction by regulating macrophages and the expression of inflammatory cytokines, thereby promoting wound healing.

The optimization of PLGA knitted mesh reinforced-collagen/chitosan scaffold for the healing of full-thickness skin defects.

Collagen-based scaffolds reveals promising to repair severe skin defects. The mechanical strength of collagen-based scaffold (CCS) limited its clinical application. Embedding poly(lactic-co-glycolic) acid (PLGA) knitted mesh into CCS improves the mechanical strength of the scaffold. This study was conducted to optimize the configuration of PLGA knitted mesh-collagen-chitosan scaffold (PCCS), and explore possible mechanisms. PLGA knitted mesh was embedded in CCS through freeze-drying method. With the PLGA knitted mesh located at the bottom, middle, or both bottom and top layers of the CCS, three kinds of PCCS were developed. A full-thickness skin wound model was established in Sprague Dawley rats to evaluate the therapeutic effects of different PCCS against CCS. The properties and healing effect of the scaffolds were investigated. Several growth factors and chemotactic factors, that is, VEGF, PDGF, CD31, α-SMA, TGF-ß1, and TGF-ß3 were analyzed and evaluated. Re-epithelialization and angiogenesis were observed in all animal groups with the treatment of three kinds of PCCS scaffolds and the CCS scaffold (control). The protein and gene expression of VEGF, PDGF, CD31, α-SMA, TGF-ß1, and TGF-ß3 showed different dynamics at different time points. Based on the healing effects and the expression of growth factors and chemotactic factors, scaffold with the PLGA knitted mesh located at the bottom layer of the CCS demonstrated the best healing effect and accelerated re-epithelialization and angiogenesis among all the scaffolds evaluated. PCCS with the PLGA mesh located in the bottom layer of the scaffold accelerated wound healing by creating a more supportive environment for re-epithelialization and angiogenesis.

The correlation between serum creatinine and burn severity and its predictive value.

This study aimed to explore the correlation between serum creatinine and burn severity and the value of predicting the outcome of patients. For this purpose, a total of 268 burn patients (BUP) were collected. According to the burn area, they were divided into mild group (MIG) (n = 125, burn area 30% - 49%), moderate group (MOG) (n = 80, burn area 50% - 79%) and severe group (SEG) (n = 63, burn area ≥ 80%). According to the prognosis, they were divided into survival group (SUG) (n = 170) and death group (DEG) (n = 98). At the same time, the control group (COG) was selected from the physical examination center of our hospital. 5 mL of fasting venous blood was collected from all BUP on the first, seventh, 14th and 21st days after admission. 5 mL of fasting venous blood was collected from the COG. Creatinine (CRE) level was measured by enzyme method. Cholinesterase (CHE) level in serum was measured by improved Ellman method. The changes of CRE and CHE in serum were compared among all groups to explore the correlation between serum creatinine and burn severity and its prediction Measure the value of patients' outcomes. Results showed that except for the first day after burn, the level of serum CRE in BUP was raised than that in the COG, and the level of serum CHE in BUP was reduced than that in the COG (P<0.05). The serum CHE level of BUP in all groups increased at first and then decreased, and the highest level was on the first day after injury. At the same time, the level of CRE in SEG was raised than that in MIG and MOG, and the level of CRE in MOG was raised than that in MIG (P<0.05). The serum CHE level of BUP in all groups decreased at first and then increased, and the lowest level was on the first day after injury. At the same time, the level of CRE in SEG was reduced to that in MIG and MOG, and the level of CRE in MOG was reduced to that in MIG (P<0.05). The level of CRE in serum of BUP in both groups increased at first and then decreased, and the level was the highest on the first day after injury. At the same time, the level of CRE in the DEG was raised than that in the SUG (P<0.05). The level of CHE in serum of BUP in both groups decreased at first and then increased, and the level was the lowest on the first day after injury. At the same time, the level of CRE in the death group was reduced than that in the SUG (P<0.05). Logistic regression analysis showed that there was statistical significance in the regression coefficients on the 1st, 7th, 14th and 21st day after burn, and on the 1st and 21st day after-burn. ROC curve analysis shows that CRE and CHE have certain value in diagnosing the prognosis of BUP, and the diagnostic value of CRE is higher. Cre level increases with the aggravation of burn patients, and ChE level decreases with the aggravation of BUP. In conclusion, Cre and ChE have certain value in diagnosing the prognosis of BUP and can be widely used in clinical practice.

Clinical Effect of Emergency Dermabrasion Combined with Biological Dressing A on Wound Microcirculation and Preventing Sepsis in Deep Degree-II Burns.

Objective: The aim of this study is to explore the clinical effect of emergency dermabrasion combined with biological dressing A on wound microcirculation and preventing sepsis in deep degree-II burns. Methods: A total of 90 patients with deep degree-II burns admitted to the hospital were retrospectively enrolled between January 2020 and January 2022. According to different treatment methods, they were divided into the control group (42 cases, biological dressing A) and the observation group (48 cases, emergency dermabrasion combined with biological dressing A). The clinical curative effect in both groups was observed. The wound repair rate and wound healing quality, and changes in levels of wound microcirculation-related indexes (serum epidermal growth factor (EGF), wound blood flow, and partial pressure of transcutaneous oxygen) and inflammatory cytokines (C-reactive protein (CPR), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT)) before treatment, at 3d and 7d after treatment were compared between the two groups. The incidence of wound infection and sepsis in both groups was recorded. Results: The wound healing time in the observation group was significantly shorter than that in the control group, and wound healing quality in the observation group was better than that in the control group (P < 0.05). At 3 d and 7d after treatment, the levels of serum EGF, wound blood flow and partial pressure of transcutaneous oxygen in both groups were all increased (P < 0.05), which were higher in the observation group than those in the control group (P < 0.05). The levels of CRP, IL-6, ESR, and PCT in both groups were all decreased (P < 0.05), which were lower in the observation group than those in the control group (P < 0.05). There was no significant difference in incidence of sepsis between observation group and control group (4.17% (2/48) vs. 7.14% (3/42)) (Fisher = 0.539). Conclusion: Emergency dermabrasion combined with biological dressing A can effectively improve wound microcirculation in patients with deep degree-II burns, promote wound healing, shorten wound healing time, improve wound healing quality, effectively control inflammatory response, and prevent sepsis.

Heme oxygenase-1 induction mitigates burn-associated early acute kidney injury via the TLR4 signaling pathway.

OBJECTIVES: Early acute kidney injury (AKI) after burn contributes to disastrous prognoses for severely burned patients. Burn-induced renal oxidative stress and secondary proinflammatory mediator release contribute to early AKI development, and Toll-like receptor (TLR) 4 regulates inflammation. Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that plays a vital role in protecting against ischemia-induced organ injury via its antioxidant properties and regulation of inflammation. We investigated the potential effect of HO-1 induction in preventing burn-induced early AKI and its related mechanism. METHODS: A classic major-burn rat model was established using a 100 °C water bath, and hemin was injected intraperitoneally immediately after the injury to induce HO-1. Histological staining and blood tests were used to assess AKI progression based on structural changes and function. Renal levels of HO-1, oxidative stress, proinflammatory mediators and TLR4-related signals were detected using ELISA, immunostaining, qRT-PCR, and western blotting. The selective TLR4 inhibitor TAK242 and TLR4 inducer LPS were introduced to determine the roles of HO-1 in burn-related renal inflammation and the TLR4 pathway. RESULTS: Hemin improved burn-induced renal histological damage and dysfunction, and this beneficial effect was related to reduced renal oxidative stress and the release of proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6 and intracellular adhesion molecule-1 (ICAM-1). Hemin downregulated the expression of TLR4 and the subsequent phosphorylation of IKKα/ß, IκBα, and NF-κB p65;. TAK242 exerted an effect similar to but weaker than hemin; and LPS reversed the antiinflammatory effect of hemin and the regulation of TLR4 signals. These results suggested that the TLR4 signaling pathway mediated the HO-1-facilitated regulation of renal inflammation after burn. CONCLUSION: The present study demonstrated that HO-1 induction prevented burn-induced early AKI by targeting renal inflammation, which was mediated via regulation of the TLR4/NF-κB signaling pathway.

Nanomaterials for the delivery of bioactive factors to enhance angiogenesis of dermal substitutes during wound healing.

Dermal substitutes provide a template for dermal regeneration and reconstruction. They constitutes an ideal clinical treatment for deep skin defects. However, rapid vascularization remains as a major hurdle to the development and application of dermal substitutes. Several bioactive factors play an important regulatory role in the process of angiogenesis and an understanding of the mechanism of achieving their effective delivery and sustained function is vital. Nanomaterials have great potential for tissue engineering. Effective delivery of bioactive factors (including growth factors, peptides and nucleic acids) by nanomaterials is of increasing research interest. This paper discusses the process of dermal substitute angiogenesis and the roles of related bioactive factors in this process. The application of nanomaterials for the delivery of bioactive factors to enhance angiogenesis and accelerate wound healing is also reviewed. We focus on new systems and approaches for delivering bioactive factors for enhancing angiogenesis in dermal substitutes.

3D bioprinting for skin tissue engineering: Current status and perspectives.

Skin and skin appendages are vulnerable to injury, requiring rapidly reliable regeneration methods. In recent years, 3D bioprinting has shown potential for wound repair and regeneration. 3D bioprinting can be customized for skin shape with cells and other materials distributed precisely, achieving rapid and reliable production of bionic skin substitutes, therefore, meeting clinical and industrial requirements. Additionally, it has excellent performance with high resolution, flexibility, reproducibility, and high throughput, showing great potential for the fabrication of tissue-engineered skin. This review introduces the common techniques of 3D bioprinting and their application in skin tissue engineering, focusing on the latest research progress in skin appendages (hair follicles and sweat glands) and vascularization, and summarizes current challenges and future development of 3D skin printing.

Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1.

Early acute kidney injury (AKI) contributes to severe morbidity and mortality in critically burned patients. Renal inflammation plays a vital role in the progression of early AKI, acting as a therapeutic target. Astaxanthin (ATX) is a strong antioxidant widely distributed in marine organisms that exerts many biological effects in trauma and disease. ATX is also suggested to have anti-inflammatory activity. Hence, we attempted to explore the role of ATX in protecting against early postburn AKI via its anti-inflammatory effects and the related mechanisms. A severely burned model was established for histological and biochemical assessments based on adult male rats. We found that oxidative stress-induced tissue inflammation participated in the development of early AKI after burn injury and that the MyD88-dependent TLR4/NF-κB pathway was activated to regulate renal inflammation. The TLR4 and NF-κB inhibitors TAK242 and PDTC showed similar effects in attenuating burn-induced renal inflammation and early AKI. Upon ATX treatment, the release of inflammatory mediators in the kidneys was downregulated, while the TLR4/MyD88/NF-κB axis was inhibited in a dose-related manner. TAK242 and PDTC could enhance the anti-inflammatory effect of high-dose ATX, whereas lipopolysaccharide (LPS) reversed its action. Furthermore, the expression of heme oxygenase (HO)-1 was upregulated by ATX in a dose-related manner. Collectively, the above data suggest that ATX protects against renal inflammation in a dose-related manner by regulating the TLR4/MyD88/NF-κB axis and HO-1 and ultimately prevents early AKI following severe burns.

Applications of Poly(caprolactone)-based Nanofibre Electrospun Scaffolds in Tissue Engineering and Regenerative Medicine.

Diseases, trauma, and injuries are highly prevalent conditions that lead to many critical tissue defects. Tissue engineering has great potentials to develop functional scaffolds that mimic natural tissue structures to improve or replace biological functions. In many kinds of technologies, electrospinning has received widespread attention for its outstanding functions, which is capable of producing nanofibre structures similar to the natural extracellular matrix. Amongst the available biopolymers for electrospinning, poly (caprolactone) (PCL) has shown favorable outcomes for tissue regeneration applications. According to the characteristics of different tissues, PCL can be modified by altering the functional groups or combining with other materials, such as synthetic polymers, natural polymers, and metal materials, to improve its physicochemical, mechanical, and biological properties, making the electrospun scaffolds meet the requirements of different tissue engineering and regenerative medicine. Moreover, efforts have been made to modify nanofibres with several bioactive substances to provide cells with the necessary chemical cues and a more in vivo like environment. In this review, some recent developments in both the design and utility of electrospun PCL-based scaffolds in the fields of bone, cartilage, skin, tendon, ligament, and nerve are highlighted, along with their potential impact on future research and clinical applications.

Regeneration of skin appendages and nerves: current status and further challenges.

Tissue-engineered skin (TES), as an analogue of native skin, is promising for wound repair and regeneration. However, a major drawback of TES products is a lack of skin appendages and nerves to enhance skin healing, structural integrity and skin vitality. Skin appendages and nerves are important constituents for fully functional skin. To date, many studies have yielded remarkable results in the field of skin appendages reconstruction and nerve regeneration. However, patients often complain about a loss of skin sensation and even cutaneous chronic pain. Restoration of pain, temperature, and touch perceptions should now be a major challenge to solve in order to improve patients' quality of life. Current strategies to create skin appendages and sensory nerve regeneration are mainly based on different types of seeding cells, scaffold materials, bioactive factors and involved signaling pathways. This article provides a comprehensive overview of different strategies for, and advances in, skin appendages and sensory nerve regeneration, which is an important issue in the field of tissue engineering and regenerative medicine.

Catechol cross-linked antimicrobial peptide hydrogels prevent multidrug-resistant Acinetobacter baumannii infection in burn wounds.

Hospital-acquired infections are common in burn patients and are the major contributors of morbidity and mortality. Bacterial infections such as Staphylococcus aureus (S. aureus) and Acinetobacter baumannii (A. baumannii) are difficult to treat due to their biofilm formation and rapidly acquiring resistance to antibiotics. This work presents a newly developed hydrogel that has the potential for treating bacterial wound infections. The hydrogel formulation is based on an antimicrobial peptide (AMP), epsilon-poly-l-lysine (EPL) and catechol, which was cross-linked via mussel-inspired chemistry between the amine and phenol groups. In vitro studies showed that EPL-catechol hydrogels possess impressive antimicrobial and antibiofilm properties toward multidrug-resistant A. baumannii (MRAB). In addition, cytotoxicity study with the clonal mouse myoblast cell line (C2C12) revealed the good biocompatibility of this hydrogel. Furthermore, we created a second-degree burn wound on the mice dorsal skin surface followed by contamination with MRAB. Our results showed that the hydrogel significantly reduced the bacterial burden by more than four orders of magnitude in infected burn wounds. Additionally, there was no significant histological alteration with hydrogel application on mice skin. Based on these results, we concluded that EPL-catechol hydrogel is a promising future biomaterial to fight against multidrug-resistant bacterial infections.

Skin perfusion pressure for the prediction of wound healing in critical limb ischemia: a meta-analysis.

INTRODUCTION: The purpose of this meta-analysis was to determine the value and efficacy of skin perfusion pressure (SPP) for the prediction of wound healing in patients with critical limb ischemia. MATERIAL AND METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched from inception until December 31, 2014 using combinations of the following keywords: skin perfusion pressure, limb ischemia, wound healing, prediction. Randomized controlled trials, 2-arm prospective studies, and retrospective studies that measured SPP in patients with limb ischemia were included. The outcome was the sensitivity and specificity of SPP for the prediction of wound healing. RESULTS: Five studies were included in the meta-analysis. The mean patient age ranged from 62.2 to 71.5 years, and the majority were male. The pooled sensitivity of SPP for the prediction of wound healing was 79.9% using 30 mm Hg as the cut-off, 67.1% using 40 mm Hg, and 76.1% for all included studies (95% CI: 73.9-84.9%, 55.8-76.8%, and 70.7-80.8%, respectively). The pooled specificity was 78.2% using 30 mm Hg, 84.2% using 40 mm Hg, and 82.1% for all included studies (95% CI: 61.5-89.0%, 74.0-90.9%, 73.7-88.3%, respectively). CONCLUSIONS: Skin perfusion pressure can accurately predict wound healing in patients with critical limb ischemia.

Non-viral gene delivery systems for tissue repair and regeneration.

Critical tissue defects frequently result from trauma, burns, chronic wounds and/or surgery. The ideal treatment for such tissue loss is autografting, but donor sites are often limited. Tissue engineering (TE) is an inspiring alternative for tissue repair and regeneration (TRR). One of the current state-of-the-art methods for TRR is gene therapy. Non-viral gene delivery systems (nVGDS) have great potential for TE and have several advantages over viral delivery including lower immunogenicity and toxicity, better cell specificity, better modifiability, and higher productivity. However, there is no ideal nVGDS for TRR, hence, there is widespread research to improve their properties. This review introduces the basic principles and key aspects of commonly-used nVGDSs. We focus on recent advances in their applications, current challenges, and future directions.

Silver nanoparticle loaded collagen/chitosan scaffolds promote wound healing via regulating fibroblast migration and macrophage activation.

Treatment of full-thickness skin defects poses significant clinical challenges including risk of infection and severe scaring. Silver nanoparticle (NAg), an effective antimicrobial agent, has provided a promising therapeutic method for burn wounds. However, the detailed mechanism remains unknown. Hence, we constructed a metallic nanosilver particles-collagen/chitosan hybrid scaffold (NAg-CCS) and investigated its potential effects on wound healing. In vitro scratch assay, immunofluorescence staining and antibacterial activity of the scaffold were all studied. In vivo NAg-CCS was applied in full-thickness skin defects in Sprague-Dawley (SD) rats and the therapeutic effects of treatment were evaluated. The results showed that NAg at a concentration of 10 ppm accelerated the migration of fibroblasts with an increase in expression of α-smooth muscle actin (α-SMA). Furthermore, in vivo studies showed increased levels of pro-inflammatory and scar-related factors as well as α-SMA, while markers for macrophage activation were up-regulated. On day 60 post transplantation of ultra-thin skin graft, the regenerated skin by NAg-CCS had a similar structure to normal skin. In summary, we demonstrated that NAg-CCS was bactericidal, anti-inflammatory and promoted wound healing potentially by regulating fibroblast migration and macrophage activation, making it an ideal dermal substitute for wound regeneration.

The progress and challenges for dermal regeneration in tissue engineering.

Wound healing is an inherent response resulting in the restoration of tissue integrity. It is a complex process involving cell migration, proliferation, differentiation, apoptosis, and the synthesis and remodeling of the extracellular matrix (ECM). The dermal tissue is an important component of skin that acts as a connecting link between the epidermis and hypodermis. The appearance of scars and contractures after autologous split-thickness skin transplantation or single epidermis diaphragm transplantation for full skin defects indicates that the dermal tissue plays an important role in skin regeneration. Theoretically, dermis cannot regenerate like the liver, bone and epidermis after being destroyed by burns or avulsion. Scarring is hard to avoid during the process of natural healing. However, if the dermis could be reconstructed perfectly, this would be a breakthrough in the methods used for wound healing. In this review, we summarize recent research about dermal regeneration and discuss the probability of advances in the field. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1208-1218, 2017.

Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation.

Pathological myofibroblasts are often involved in skin scarring via generating contractile force and over-expressing collagen fibers, but no compound has been found to inhibit the myofibroblasts without showing severe toxicity to surrounding physiological cells. Here we report that di-rhamnolipid, a biosurfactant secreted by Pseudomonas aeruginosa, showed potent effects on scar therapy via a unique mechanism of targeted killing the myofibroblasts. In cell culture, the fibroblasts-derived myofibroblasts were more sensitive to di-rhamnolipid toxicity than fibroblasts at a concentration-dependent manner, and could be completely inhibited of their specific functions including α-SMA expression and collagen secretion/contraction. The anti-fibrotic function of di-rhamnolipid was further verified in rabbit ear hypertrophic scar models by presenting the significant reduction of scar elevation index, type I collagen fibers and α-SMA expression. In this regard, di-rhamnolipid treatment could be suggested as a therapy against skin scarring.

Retrospective data about the catheter-related complications and management in massive bus burn casualties.

PURPOSE: This is a single-center, descriptive report of the management and complications of venous catheter use in 19 severely burned passengers from a bus fire that occurred on July 5, 2014, in Hangzhou. METHODS: We recorded the parameters of the catheters insertion and indwelling. Sampling of each removed catheter was conducted to monitor for catheter-related infections. Bedside ultrasound screening was performed for recording central venous catheter (CVC)-related complications. RESULTS: Of the 174 venous accesses placed, 108 were CVCs. 27 (25.0%) catheter tip cultures (CTC) were positive; 12 (11.1%) were catheter-related blood stream infections (CRBSI). Acinetobacter baumannii was the most prominent bacterial infection for both CTC- (55.56%) and CRBSI- (75.00%) positive catheters. CTC- and CRBSI-positive rates were higher during the emergency stage, and both dropped rapidly after reform measures (chi-square test, p = 0.003), and all were negative after the no.8 catheters. Accumulative regression results indicated that total body surface area burned (TBSA), number of catheters, days of indwelling, and bloodstream infections were independently associated with CTC results, while gender and number of catheters were independently associated with CRBSI results. 1 femur vein thrombosis was detected and cured. CONCLUSIONS: Bedside ultrasound and professional IV team for CVC management are pivotal for massive burn victims. Their intervention helps control CVC-related infections and other complications. A. baumannii was the most frequent bacterial infection found in both CTC- and CRBSI-positive catheters. Several most important factors associated with catheter-related infections were concluded. This information alerts us to watch for patients with such warning factors.

Polyurethane membrane/knitted mesh-reinforced collagen-chitosan bilayer dermal substitute for the repair of full-thickness skin defects via a two-step procedure.

The advent of dermal substitutes provides a revolutionary strategy for the repair and reconstruction of deep skin defects. Dermal substitutes form a regenerative template that provides the porous structure and mechanical support necessary to guide cell migration, deposition of the extracellular matrix (ECM) and angiogenesis. Commercially available dermal substitutes, particularly collagen-based dermal scaffolds, are widely used in clinical practice. However, the poor mechanical properties of collagen-based dermal scaffolds compromise their biological effects, as well as the repair outcomes. Here, we describe a bilayer dermal substitute prepared by integrating a hybrid dermal scaffold with a polyurethane (PU) membrane to obtain a PU membrane/knitted mesh-reinforced collagen-chitosan bilayer dermal substitute (PU-PLGAm/CCS). The morphology of PU-PLGAm/CCS was investigated and, to characterize the effects of PU-PLGAm/CCS on tissue regeneration, dermal substitutes were transplanted to repair full-thickness skin wounds in Sprague-Dawley rats using a two-step surgical procedure. These results were then compared with those obtained using the PELNAC™ Artificial Dermis. In the weeks after the first operation, wound changes were analysed based on macroscopic observations, and tissue specimens were harvested for histology, immunohistochemistry, immunofluorescence real-time quantitative PCR, and Western blotting analysis. Following the second operation (i.e., transplantation of split-thickness skin grafts), the repair outcomes were investigated based on the mechanical strength and ECM expression. PU-PLGAm/CCS significantly inhibited wound contracture, promoted angiogenesis, and facilitated the ordered arrangement of neotissue, such that the repair outcomes were improved in the PU-PLGAm/CCS group compared with the PELNAC™ group. In conclusion, the favourable microstructure and structural stability of dermal substitutes facilitated tissue regeneration. PU-PLGAm/CCS achieved a balance between porous structure, biocompatibility and mechanical properties for dermal regeneration by integrating the advantages of biological and synthetic biomaterials, which demonstrates its potential for skin tissue engineering.

Opuntia Extract Reduces Scar Formation in Rabbit Ear Model: A Randomized Controlled Study.

The purpose of this article is to investigate the effect of Opuntia stricta H (Cactaceae) extract on suppression of hypertrophic scar on ventral surface wounds of rabbit ears. Full thickness skin defection was established in a rabbit ear to simulate hypertrophic scar. Opuntia extract was sprayed on the wounds in the experimental group, and normal saline was used in the control group. After the wounds healed with scar formation, the hypertrophic scar tissue was harvested on days 22, 39, and 54 for histological analysis. The expression of type I and type III collagen and matrix metalloproteinase-1 (MMP-1) were evaluated by immunohistochemistry and real-time quantitative polymerase chain reaction. The results indicated that the scar of the control group is more prominent compared with the opuntia extract group. The expression of type I collagen in the opuntia extract group was lower than the control group, while type III collagen in opuntia extract group gradually increased and exceeded control group. The expression of MMP-1 decreased in the opuntia extract group, while the control group increased over time, but the amount of MMP-1 was much higher than that in the control group on day 22. In conclusion, opuntia extract reduces hypertrophic scar formation by means of type I collagen inhibition, and increasing type III collagen and MMP-1.T he novel application of opuntia extract may lead to innovative and effective antiscarring therapies.