Ontogeny of expression of transforming growth factor-βand its receptors and their possible relationship with scarless or scar-forming healing in human fetal and postnatal skins

Fetal eutaneous wounds that oeeur in earlygestation heal without sear formation.Althoughmueh work has been done to eharaeterize the roleof transforming growth

Piezoelectric film promotes skin wound healing with enhanced collagen deposition and vessels regeneration via upregulation of PI3K/AKT

Skin wounds are common in accidental injuries,and the intricacies of wound repair are closely linked to endogenous electric fields.Electrical stimulation plays a pivotal role in the restorative processes of skin injuries,encompassing collagen deposition,angiogenesis,inflammation,and re-epithelialization.Employing electrical stimulation therapy replicates and enhances the effects of endogenous wound electric fields by applying an external electric field to the wound site,thereby promoting skin wound healing.In this study,we developed a self-powered repetitive mechanical impacts-electrical stimulation(RMI-ES)system utilizing a BaTiO3/polydimethylsiloxane(PDMS)piezoelectric composite film.Compared to conventional electrical stimulation devices,the fabricated piezoelectric composite film efficiently harvests energy from the pressure applied by the stimulation device and the tensile force occurring during natural rat activities.The results demonstrated that piezoelectric stimulation generated by the composite membrane expedited the cell cycle,promoting fibroblast proliferation.Additionally,piezoelectric stimulation induced favorable changes in fibroblast gene expression,including increased expression of transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF),collagen 1,collagen 3,vascular endothelial growth factor(VEGF),and alpha-smooth muscle actin(α-SMA),while reducing interleukin-6(IL-6)expression.Transcriptome analysis revealed that piezoelectric stimulation may induce fibroblast migration,proliferation,and collagen expression by influencing PI3K/AKT serine/threonine kinase(AKT)pathways.Further confirmation through the addition of the PI3K inhibitor LY294002 validated that piezoelectric stimulation can regulate the repair process after skin injury through the pathway.Importantly,in vivo results demonstrated that the electric field at the wound site effectively promoted wound healing,reduced inflammation,and stimulated collagen deposition and neovascularization.This study emphasizes the role of the piezoelectric membrane as an effective,safe,and battery-free electrical stimulator crucial for skin wound healing.

Recombinant human epidermal growth factor combined with vacuum sealing drainage for wound healing in Bama pigs

Background:Vacuum sealing drainage(VSD)and epidermal growth factor(EGF)both play an important role in the treatment of wounds.This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF.Methods:We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations(0,1,5,10,and 100ng/ml)and different EGF action times(2,10,and 30min).A full-thickness skin defect model was established using male,30-week-old Bama pigs.The experiment included groups as follows:routine dressing change after covering with sterile auxiliary material(Control),continuous negative pressure drainage of the wound(VSD),continuous negative pressure drainage of the wound and injection of EGF 10min followed by removal by continuous lavage(V+E 10min),and continuous negative pressure drainage of the wound and injection of EGF 30min followed by removal by continuous lavage(V+E 30min).The wound healing rate,histological repair effect and collagen deposition were compared among the four groups.Results:An EGF concentration of 10ng/ml and an action time of 10min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells.The drug dispersion effect was better than drug infusion after bolus injection effect,and the contact surface was wider.Compared with other groups,the V+E 10min group promoted wound healing to the greatest extent and obtained the best histological score.Conclusions:A recombinant human epidermal growth factor(rhEGF)concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro.VSD combined with rhEGF kept in place for 10min and then washed,can promote wound healing better than the other treatments in vitro.

Fabrication and Evaluation of Porous Keratin/chitosan(KCS) Scaffolds for Effectively Accelerating Wound Healing

Objective To develop a dressing with desired antibacterial activity, good water maintaining ability and mechanical properties for wound healing and skin regeneration. Methods The chitosan with different concentrations were added in keratin solution to form porous keratin/chitosan（KCS） scaffolds. The morphological characteristics, chemical composition, wettability, porosity, swelling ratio and degradation of the scaffolds were evaluated. The antibacterial activity was tested by using S. aureus and E. coli suspension for 2 h. And L929 fibroblast cells culture was used to evaluate the cytotoxicity of the KCS scaffolds. Results The adding of chitosan could increase the hydrophobicity, decrease porosity, swelling ratio and degradation rate of the KCS porous scaffolds. Mechanical properties of KCS scaffolds could be enhanced and well adjusted by chitosan. KCS scaffolds could obviously decrease bacteria number. The proliferation of fibroblast cells in porous KCS patch increased firstly and then decreased with the increase of chitosan concentration. It was appropriate to add 400 μg/m L chitosan to form porous KCS scaffold for achieving best cell attachment and proliferation compared with other samples. Conclusion The porous KCS scaffold may be used as implanted scaffold materials for promoting wound healing and skin regeneration.

用于实时皮肤创面愈合的超强工程化蛋白凝聚体黏合剂

Adhesives have attracted a great deal of attention as an advanced modality in biomedical engineering because of their unique wound management behavior.However,it is a grand challenge for current adhesive systems to achieve robust adhesion due to their tenuous interfacial bonding strength.Moreover,the absence of dynamic adaptability in conventional chemical adhesives restricts neoblasts around the wound from migrating to the site,resulting in an inferior tissue-regeneration effect.Herein,an extracellular matrix-derived biocomposite adhesive with robust adhesion and a real-time skin healing effect is well-engineered.Liquid–liquid phase separation is well-harnessed to drive the assembly of the biocomposite adhesive,with the active involvement of supramolecular interactions between chimeric protein and natural DNA,leading to a robustly reinforced adhesion performance.The bioadhesive exhibits outstanding adhesion and sealing behaviors,with a sheared adhesion strength of approximately 18 MPa,outperforming its reported counterparts.Moreover,the engineered bioderived components endow this adhesive material with biocompatibility and exceptional biological functions including the promotion of cell proliferation and migration,such that the use of this material eventually yields real-time in situ skin regeneration.This work opens up novel avenues for functionalized bioadhesive engineering and biomedical translations.

Chitosan@Puerarin hydrogel for accelerated wound healing in diabetic subjects by miR-29ab1 mediated inflammatory axis suppression

Wound healing is one of the major global health concerns in patients with diabetes.Overactivation of pro-inflammatory M1 macrophages is associated with delayed wound healing in diabetes.miR-29ab1 plays a critical role in diabetes-related macrophage inflammation.Hence,inhibition of inflammation and regulation of miR-29 expression have been implicated as new points for skin wound healing.In this study,the traditional Chinese medicine,puerarin,was introduced to construct an injectable and self-healing chitosan@puerarin(C@P)hydrogel.The C@P hydrogel promoted diabetic wound healing and accelerated angiogenesis,which were related to the inhibition of the miR-29 mediated inflammation response.Compared to healthy subjects,miR-29a and miR-29b1 were ectopically increased in the skin wound of the diabetic model,accompanied by upregulated M1-polarization,and elevated levels of IL-1βand TNF-α.Further evaluations by miR-29ab1 knockout mice exhibited superior wound healing and attenuated inflammation.The present results suggested that miR-29ab1 is essential for diabetic wound healing by regulating the inflammatory response.Suppression of miR-29ab1 by the C@P hydrogel has the potential for improving medical approaches for wound repair.

Reversibly immortalized keratinocytes(iKera)facilitate re-epithelization and skin wound healing:Potential applications in cell-based skin tissue engineering

Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.

The Influence of Different Surgical Schemes on the Healing and Cosmetic Effects of Skin Lesions

Objective To analyze the effects of different surgical procedures on the healing and cosmetic effects of skin lesions.Methods 102 patients with skin defects after skin tumor resection in our hospital from January 2018 to December 2019 were selected and randomly divided into observation group and control group.The control group was treated with a traditional skin flap transplantation,while the observation group was treated with a skin stretch closure device.The effective rate,bleeding volume,wound healing time,total scar length,short-term and long-term complications and patient satisfaction were compared between the two groups.Results The effective rates of the observation group and the control group were 90.2%and88.24%,there was no significant difference in the treatment efficiency between the two groups(P>0.05),but there were significant differences in the amount of bleeding,the time of wound healing and the total length of postoperative scars between the two groups(all P<0.05);the short-term complication rates of the observation group and the control group were 5.88%and 19.61%,and long-term complications rate was 1.96%and 13.73%.The difference in the incidence of short-term and long-term complications between the two groups was statistically significant(all P<0.05);the satisfaction rate of patients in the observation group and the control group was 90.2%and 72.55%,the difference was statistically significant(P<0.05).Conclusion The former can effectively shorten wound healing time and scar length,reduce the incidence of short-term and long-term complications,and improve patients’satisfaction with the treatment,which is worthy of promotion.

Sustained release of magnesium and zinc ions synergistically accelerates wound healing

Skin wounds are a major medical challenge that threaten human health.Functional hydrogel dressings demonstrate great potential to promote wound healing.In this study,magnesium(Mg)and zinc(Zn)are introduced into methacrylate gelatin(GelMA)hydrogel via low-temperature magnetic stirring and photocuring,and their effects on skin wounds and the underlying mechanisms are investigated.Degradation testing confirmed that the GelMA/Mg/Zn hydrogel released magnesium ions(Mg^(2+))and zinc ions(Zn^(2+))in a sustained manner.The Mg^(2+) and Zn^(2+)not only enhanced the migration of human skin fibroblasts(HSFs)and human immortalized keratinocytes(HaCats),but also promoted the transformation of HSFs into myofibroblasts and accelerated the production and remodeling of extracellular matrix.Moreover,the GelMA/Mg/Zn hydrogel enhanced the healing of full-thickness skin defects in rats via accelerated collagen deposition,angiogenesis and skin wound re-epithelialization.We also identified the mechanisms through which GelMA/Mg/Zn hydrogel promoted wound healing:the Mg^(2+) promoted Zn^(2+)entry into HSFs and increased the concentration of Zn^(2+)in HSFs,which effectively induced HSFs to differentiate into myofibroblasts by activating the STAT3 signaling pathway.The synergistic effect of Mg^(2+) and Zn^(2+)promoted wound healing.In conclusion,our study provides a promising strategy for skin wounds regeneration.

One-step approach for full-thickness skin defect reconstruction in rats using minced split-thickness skin grafts with Pelnac overlay

Background:Split-thickness skin grafting is the current gold standard for the treatment of traumatic skin loss.However,for patients with extensive burns,split-thickness skin grafting is limited by donor skin availability.Grafting split-thickness skin minced into micrografts increases the expansion ratio but may reduce wound repair quality.Dermal substitutes such as Pelnac can enhance the healing of full-thickness skin wounds,but their application currently requires two surgeries.The present study investigated whether it is possible to repair full-thickness skin defects and improve wound healing quality in a single surgery using Pelnac as an overlay of minced split-thickness skin grafts in a rat model.Methods:A full-thickness skin defect model was established using male Sprague-Dawley rats of 10 weeks old.The animals were randomly divided into control and experimental groups in which Vaseline gauze and Pelnac,respectively,were overlaid on minced split-thickness skin grafts to repair the defects.Wound healing rate and quality were compared between the two groups.For better illustration of the quality of wound healing,some results were compared with those obtained for normal skin of rats.Results:We found that using Pelnac as an overlay for minced split-thickness skin grafts accelerated wound closure and stimulated cell proliferation and tissue angiogenesis.In addition,this approach enhanced collagen synthesis and increased the formation of basement membrane and dermis as well as the expression of growth factors related to wound healing while reducing scar formation.Conclusions:Using minced split-thickness skin grafts overlaid with Pelnac enables the reconstruction of fullthickness skin defects in a single step and can increase the healing rate while improving the quality of wound healing.

Zinc-based metal organic framework with antibacterial and anti-inflammatory properties for promoting wound healing

The synergistic effect of antibacterial and anti-inflammatory is needed to overcome the problem of wound healing difficulties.Based on the favorable antibacterial and anti-inflammatory effect of zinc ions(Zn^(2+))and the physicochemical properties of metal organic frameworks(MOFs),we prepared nanosized zinc-based MOF:Zn-BTC with the ability to slowly release Zn^(2+).In cellular levels,Zn-BTC possessed lower toxicity to fibroblasts and enhanced capacity of cell proliferation and migration.It also had good bactericidal effect on multiple drug-resistant bacteria by reducing 41.4%MRSA and 47.2%Escherichia coli.In addition,Zn-BTC also displayed the ability of lowering the expression of antioxidant genes:superoxide dismutase 1,superoxide dismutase 2 and interleukin 6,and enhancing the expression of wound healing genes:transforming growth factors-b and type I collagen.Finally,it also demonstrated that Zn-BTC could effectively improve the skin wound healing of SD rats and had no toxicity on major organs.The favorable biocompatibility,antibacterial and anti-inflammatory properties of Zn-BTC gave a new insight of designing novel MOFs for promoting skin wound healing.

L-Arginine based polyester amide/hyaluronic acid hybrid hydrogel with dual anti-inflammation and antioxidant functions for accelerated wound healing

Nowadays, there are still many challenges to skin regeneration. As a new type of skin substitute, hydrogel has emerging gradually with its excellent properties. However, it is still a challenge to combine with biological active agents to facilitate skin regeneration. Under the circumstance, we synthesized argininebased poly(ester amide)(Arg-PEA) and hyaluronic acid(HA-MA), and combined them into new hybrid hydrogels via photo-crosslinking. We found that the internal structure and physicochemical properties of hybrid hydrogels were greatly improved with the increase of content of Arg-PEA. Therefore, we designed hybrid hydrogels with 5 wt% and 10 wt% of Arg-PEA content, respectively. Besides, we selected the corresponding anti-inflammatory(CRP, TNF-α) indicators to detect the anti-inflammatory properties of the hybrid hydrogels at the protein level, and the corresponding antioxidant indicators(SOD, GSH/GSSG, MDA)were selected to investigate the antioxidant properties of hybrid hydrogels at the cellular level in vitro.In addition, we also selected relevant genes to test the effect of hybrid hydrogels on fibrosis and vascularization in the process of skin wound healing in vitro and verified them in vivo with a mouse dorsum wound model. The results confirmed that Arg-PEA/HA-MA(AH) hybrid hydrogel was a prospective scaffold material for skin regeneration.

Applications of PLA in modern medicine

Polylactic acid(PLA)is a versatile biopolymer.PLA is synthesized with ease from abundant renewable resources and is biodegradable.PLA has shown promise as a biomaterial in a plethora of healthcare applications such as tissue engineering or regenerative medicine,cardiovascular implants,dental niches,drug carriers,orthopedic in-terventions,cancer therapy,skin and tendon healing,and lastly medical tools/equipment.PLA has demonstrated instrumental importance as a three-dimensionally(3D)printable biopolymer,which has further been bolstered by its role during the Coronavirus Disease of 2019(Covid-19)global pandemic.As an abundant filament,PLA has created desperately needed personal protective equipment(PPE)and ventilator modifications.As polymer chemistry continues to advance,so too will the applications and continued efficacy of PLA-based modalities.