Chuangang You

The progress of silver nanoparticles in the antibacterial mechanism, clinical application and cytotoxicity.

Nanotechnology is a highly promising field, with nanoparticles produced and utilized in a wide range of commercial products. Silver nanoparticles (AgNPs) has been widely used in clothing, electronics, bio-sensing, the food industry, paints, sunscreens, cosmetics and medical devices, all of which increase human exposure and thus the potential risk related to their short- and long-term toxicity. Many studies indicate that AgNPs are toxic to human health. Interestingly, the majority of these studies focus on the interaction of the nano-silver particle with single cells, indicating that AgNPs have the potential to induce the genes associated with cell cycle progression, DNA damage and mitochondrial associated apoptosis. AgNPs administered through any method were subsequently detected in blood and were found to cause deposition in several organs. There are very few studies in rats and mice involving the in vivo bio-distribution and toxicity, organ accumulation and degradation, and the possible adverse effects and toxicity in vivo are only slowly being recognized. In the present review, we summarize the current data associated with the increased medical usage of nano-silver and its related nano-materials, compare the mechanism of antibiosis and discuss the proper application of nano-silver particles.

The roles of knitted mesh-reinforced collagen-chitosan hybrid scaffold in the one-step repair of full-thickness skin defects in rats.

Full-thickness skin defects represent a significant and urgent clinical problem. Dermal substitutes serving as a regenerative template to induce dermal reconstruction provide a promising method to treat serious skin defects. Although collagen-chitosan dermal scaffolds display good biocompatibility and a suitable porous structure for angiogenesis and tissue regeneration, their poor mechanical properties compromise their application. To develop a well-supported dermal substitute, a poly(l-lactide-co-glycolide) (PLGA) knitted mesh was fabricated and integrated with collagen-chitosan scaffold (CCS) to obtain a PLGA knitted mesh-reinforced CCS (PLGAm/CCS). The morphology of this PLGAm/CCS was investigated in vitro. To characterize the tissue response, specifically angiogenesis and tissue regeneration, the PLGAm/CCS was transplanted in combination with thin split-thickness autografts to repair full-thickness skin wounds using a one-step surgical procedure in Sprague-Dawley rats. These results were then compared with CCSs. At weeks 2, 4 and 8 after the operation, the healing wounds were imaged to analyse wound changes, and tissue specimens were harvested for histology, immunohistochemistry, real-time quantitative polymerase chain reaction and Western blot analysis. The results demonstrated that collagen-chitosan sponge in the PLGAm/CCS remained porous, interconnected and occupied the openings of PLGA mesh, and the incorporation of the PLGA knitted mesh into CCS improved the mechanical strength with little influence on its mean pore size and porosity. Following transplantation, PLGAm/CCS inhibited wound contraction, and effectively promoted neotissue formation and blood vessel ingrowth. In conclusion, the mechanical strength of the scaffolds plays an important role in the process of tissue regeneration and vascularization. The ability of PLGAm/CCS to promote angiogenesis and induce in situ tissue regeneration demonstrates its potential in skin tissue engineering.

Fabrication and characterization of poly(L-lactide-co-glycolide) knitted mesh-reinforced collagen-chitosan hybrid scaffolds for dermal tissue engineering.

Mechanical properties are essential considerations for the design of porous scaffolds in the field of tissue engineering. To develop a well-supported hybrid dermal substitute, poly(L-lactide-co-glycolide) (PLGA) yarns were knitted into a mesh with relative fixed loops, followed by incorporation into collagen-chitosan scaffolds (CCS) to obtain PLGA knitted mesh-reinforced CCS (PLGAm/CCS). The morphology and tensile strength in both the dry and wet state of PLGAm/CCS were investigated in vitro. To characterize the tissue response, specifically angiogenesis and tissue regeneration, PLGAm/CCS was embedded subcutaneously in Sprague-Dawley rats and compared with two control implants, i.e., PLGA mesh (PLGAm) and CCS. At weeks 1, 2, and 4 post surgery, tissue specimens were harvested for histology, immunohistochemistry, real-time quantitative PCR and Western blot analysis. These results demonstrated that the incorporation of PLGA knitted mesh into CCS can improve the mechanical strength with little influence on its mean pore size and porosity. After implantation, PLGAm/CCS can resist contraction and promote cell infiltration, neotissue formation, and blood vessel ingrowth, effectively. In conclusion, the mechanical strength of scaffolds can play a synergetic role in tissue regeneration and vascularization by maintaining its 3D microstructure. The ability of PLGAm/CCS to promote angiogenesis and induce in situ tissue formation demonstrates its strong potential in the field of skin tissue engineering.

Applications of knitted mesh fabrication techniques to scaffolds for tissue engineering and regenerative medicine.

Knitting is an ancient and yet, a fresh technique. It has a history of no less than 1,000 years. The development of tissue engineering and regenerative medicine provides a new role for knitting. Several meshes knitted from synthetic or biological materials have been designed and applied, either alone, to strengthen materials for the patching of soft tissues, or in combination with other kinds of biomaterials, such as collagen and fibroin, to repair or replace damaged tissues/organs. In the latter case, studies have demonstrated that knitted mesh scaffolds (KMSs) possess excellent mechanical properties and can promote more effective tissue repair, ligament/tendon/cartilage regeneration, pipe-like-organ reconstruction, etc. In the process of tissue regeneration induced by scaffolds, an important synergic relationship emerges between the three-dimensional microstructure and the mechanical properties of scaffolds. This paper presents a comprehensive overview of the status and future prospects of knitted meshes and its KMSs for tissue engineering and regenerative medicine.

Astaxanthin Attenuates Early Acute Kidney Injury Following Severe Burns in Rats by Ameliorating Oxidative Stress and Mitochondrial-Related Apoptosis

Early acute kidney injury (AKI) is a devastating complication in critical burn patients, and it is associated with severe morbidity and mortality. The mechanism of AKI is multifactorial. Astaxanthin (ATX) is a natural compound that is widely distributed in marine organisms; it is a strong antioxidant and exhibits other biological effects that have been well studied in various traumatic injuries and diseases. Hence, we attempted to explore the potential protection of ATX against early post burn AKI and its possible mechanisms of action. The classic severe burn rat model was utilized for the histological and biochemical assessments of the therapeutic value and mechanisms of action of ATX. Upon ATX treatment, renal tubular injury and the levels of serum creatinine and neutrophil gelatinase-associated lipocalin were improved. Furthermore, relief of oxidative stress and tubular apoptosis in rat kidneys post burn was also observed. Additionally, ATX administration increased Akt and Bad phosphorylation and further down-regulated the expression of other downstream pro-apoptotic proteins (cytochrome c and caspase-3/9); these effects were reversed by the PI3K inhibitor LY294002. Moreover, the protective effect of ATX presents a dose-dependent enhancement. The data above suggested that ATX protects against early AKI following severe burns in rats, which was attributed to its ability to ameliorate oxidative stress and inhibit apoptosis by modulating the mitochondrial-apoptotic pathway, regarded as the Akt/Bad/Caspases signalling cascade.

A review of treatment strategies for hydrofluoric acid burns: Current status and future prospects

Hydrofluoric acid (HF), a dangerous inorganic acid, can cause severe corrosive effects and systemic toxicity. HF enters the human body via where it contacts, such as skin and mucosa, alimentary and respiratory tracts, and ocular surfaces. In the recent years, the incidence of HF burn has tended to increase over time. The injury mechanism of HF is associated primarily with the massive absorption of HF and the release of hydrogen ions. Correct diagnosis and timely treatment are especially important for HF burns. The critical procedure to treat HF burn is to prevent on-going HF absorption, and block the progressive destruction caused by fluoride ions. Due to the distinct characteristics of HF burns, the topical treatment, as well as systemic support, has been emphasised. Whereas, management of patients with HF burns remains a great challenge in some situations. To date, there has been no widely accepted protocol for the rescue of HF burns, partly due to the diversity of HF burns. This paper overviews the current status and problems of treatment strategies for HF burns, for the purpose of promoting the future researches and improvement.

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.

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.

In vitro evaluation of Panax notoginseng Rg1 released from collagen/chitosan-gelatin microsphere scaffolds for angiogenesis

BackgroundThe emergence of skin substitutes provides a new approach for the treatment of wound repair and healing. The consistent and steady release of angiogenic factors is an important factor in the promotion of angiogenesis in skin substitutes, which usually lack, yet need, a vascular network.MethodsIn this study, ginsenoside Rg1, a natural compound isolated from Panax notoginseng (PNS), was incorporated into a collagen/chitosan-gelatin microsphere (CC-GMS) scaffold. The cumulative release kinetics were evaluated, and the effects of the released Rg1 on human umbilical vein endothelial cells (HUVECs) behavior, including proliferation, migration, tube formation, cell-cycle progression, cell apoptosis, and vascular endothelial growth factor (VEGF) secretion, were investigated. Additionally, HUVECs were cultured on the CC-GMS scaffold to test its biocompatibility. Standard Rg1 and VEGF were used as positive controls.ResultsThe results indicated that the CC-GMS scaffold had good release kinetics. The Rg1 released from the CC-GMS scaffold did not lose its activity and had a significant effect on HUVEC proliferation. Both Rg1 and VEGF promoted HUVEC migration and tube formation. Rg1 did not induce HUVEC apoptosis but instead promoted HUVEC progression into the S and G2/M phases of the cell cycle. Rg1 significantly increased VEGF secretion compared with that in the control group. HUVEC culture on the CC-GMS scaffold indicated that this scaffold has good biocompatibility and that CC-GMS scaffolds containing different concentrations of Rg1 promote HUVEC attachment in a dose- and time-dependent manner.ConclusionsRg1 may represent a new class of angiogenic agent that can be encapsulated in CC-GMS scaffolds to exert angiogenic effects in engineered tissue.

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.