Cloning and screening of scarless healing-related gene(s) in rabbit skin

Background: Over the past years, scientists have been working on the mechanisms of the scarless healing. The remarkable phenotypic differences between fetal and adult healing may lead us to find out their characteristics in genetics, which represent potentially important mechanisms to explain the differences in the quality of wound repair observed in fetus versus adult tissues. Methods: Middle laparotomy and hysterotomy were performed on pregnant rabbits on 20-day gestation to expose the fetal back, and longitudinal incision which penetrated full skin was made on the back of fetus. The trauma fetus skin was harvested at 12 h post-operation (FT), the fetus control (FC) and trauma adult skin (AT) were taken at the same time. dscDNA was synthesized from total RNA of skin samples with SMART technology. An improved suppression subtractive hybridization (SSH) method was applied to analyze the samples. Having taken one of the three samples as Tester respectively, the other two together as Drivers, one forward and two reverse hybridization products were gotten. Having amplified by selective PCR, the products were inserted into vector, and then transferred into E.coli HB101. The colonies were screened by electrophoresis, reverse Northern afterwards, and the positive clones were sequenced. BLAST in NCBI was performed to compare and analyze the positive clones (expressed sequence Tag, ESTs). Results: Totally 298 clones were gotten and 61 positive clones were obtained after screening. The 61 selected positive clones were sequenced and 54 sequences were goten. Conclusion: Instead of traditional SSH, an improved SSH with 2 Drivers was applied in the experiment. The improved program is reasonable and correct in both theory and practice.

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

Emerging biomedical technologies for scarless wound healing

Complete wound healing without scar formation has attracted increasing attention,prompting the development of various strategies to address this challenge.In clinical settings,there is a growing preference for emerging biomedical technologies that effectively manage fibrosis following skin injury,as they provide high efficacy,cost-effectiveness,and minimal side effects compared to invasive and costly surgical techniques.This review gives an overview of the latest developments in advanced biomedical technologies for scarless wound management.We first introduce the wound healing process and key mechanisms involved in scar formation.Subsequently,we explore common strategies for wound treatment,including their fabrication methods,superior performance and the latest research developments in this field.We then shift our focus to emerging biomedical technologies for scarless wound healing,detailing the mechanism of action,unique properties,and advanced practical applications of various biomedical technology-based therapies,such as cell therapy,drug therapy,biomaterial therapy,and synergistic therapy.Finally,we critically assess the shortcomings and potential applications of these biomedical technologies and therapeutic methods in the realm of scar treatment.

Anti-oxidant anti-inflammatory and antibacterial tannin-crosslinked citrate-based mussel-inspired bioadhesives facilitate scarless wound healing

The revolutionary role of tissue adhesives in wound closure,tissue sealing,and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing.In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators(exemplified by sodium periodate and silver nitrate),herein,the natural polyphenolic compound tannic acid(TA)was used to achieve near instantaneous(<25s),hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant,anti-inflammatory,and antimicrobial activities(3A-TCMBAs).The resulting materials were self-healing and possessed low swelling ratios(<60%)as well as considerable mechanical strength(up to~1.0 MPa),elasticity(elongation~2700%),and adhesion(up to 40 kPa).The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability,favorable cytocompatibility and cell migration,as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli(>90%bacterial death upon near-infrared(NIR)irradiation).In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs+NIR treatment could promote wound closure and collagen deposition and improve the collagen Ⅰ/Ⅲ ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines.Further,phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation&remodeling of the extracellular matrix(ECM)in the late stage(supported by phased CD31(platelet endothelial cell adhesion molecule-1)PDGF(platelet-derived growth factor)and VEGF(vascular endothelial growth factor)expression as well as elevated matrix metalloprotein-9(MMP-9)expression on day 21),resulting in scarless wound healing.The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant,new class of bioadhesive.

Nano oxygen chamber by cascade reaction for hypoxia mitigation and reactive oxygen species scavenging in wound healing

Hypoxia,excessive reactive oxygen species(ROS),and impaired angiogenesis are prominent obstacles to wound healing following trauma and surgical procedures,often leading to the development of keloids and hypertrophic scars.To address these challenges,a novel approach has been proposed,involving the development of a cascade enzymatic reaction-based nanocarriers-laden wound dressing.This advanced technology incorporates superoxide dismutase modified oxygen nanobubbles and catalase modified oxygen nanobubbles within an alginate hydrogel matrix.The oxygen nano chamber functions through a cascade reaction between superoxide dismutase and catalase,wherein excessive superoxide in the wound environment is enzymatically decomposed into hydrogen peroxide,and this hydrogen peroxide is subsequently converted into oxygen by catalase.This enzymatic cascade effectively controls wound inflammation and hypoxia,mitigating the risk of keloid formation.Concurrently,the oxygen nanobubbles release oxygen continuously,thus providing a sustained supply of oxygen to the wound site.The oxygen release from this dynamic system stimulates fibroblast proliferation,fosters the formation of new blood vessels,and contributes to the overall wound healing process.In the rat full-thickness wound model,the cascade reaction-based nano oxygen chamber displayed a notable capacity to expedite wound healing without scarring.Furthermore,in the pilot study of porcine full-thickness wound healing,a notable acceleration of tissue repair was observed in the conceived cascade reaction-based gel treated group within the 3 days post-surgery,which represents the proliferation stage of healing process.These achievements hold significant importance in ensuring the complete functional recovery of tissues,thereby highlighting its potential as a promising approach for enhancing wound healing outcomes.

The expression characteristics and biological significance of bFGF,EGF,TGF-β isoforms and their receptors in skins from fetus and adult

Objective:To observe the localization and expression characteristics of alpha-smooth muscle actin (AS-MA),basic fibroblast growth factor (bFGF),epidermal growth factor (EGF),transforming growth factor-β(TGF-β) isoforms,and their receptors in fetal and adult skins in order to explore their potential biological significance.Methods;The expression and the distribution of ASMA,bFGF,EGF,TGF-βisoforms,and their receptors were de-tected with immunohistochemistry and histopathology methods in 36 skin specimens....

Analysis of differentially expressed genes in fetal skin of scarless and scar-forming periods of gestational rats

Objective ：To study the differences of gene expression between earlier gestational skin and later gestational skin of rats with the aids of single primer amplification （SPA） and high-density oligonucleotide DNA array to understand the molecular mechanism of scarless healing. Methods： Total RNAs were isolated from fetal rat skin of the scarless（E15） and scar-forming （ E18 ） periods of gestation （term = 21.5 days）. The RNAs from earlier gestational skin （ EGS ） and later gestational skin （ LGS ） were both reversely transcribed to cDNAs, then labeled with the incorporation of fluorescent dCTP for preparing the hybridization probes by SPA method. The mixed probes were then hybridized to the oligonucleotide DNA arrays which contained 5 705 probes representing 5 705 rat genes. After highly stringent washing, these DNA arrays were scanned for fluorescent signals to display the differentially expressed genes between the 2 groups of skin. Results. Among 5 705 rat genes, there were 53 genes （0.93%） with differentially expressed levels between EGS and LGS groups, 27 genes, including fibroblast growth factor 2 （ FGF2 ） and follistatin were up-regulated （0.47%） and 26 genes were down-regulated （0.46%） in fetal skin during scarless period versus scar-forming period. Higher expressions of FGF2 and follistatin in EGS than those in LGS were also revealed by RT-PCR method. Conclusions： High-density oligonucleotide DNA array provided a powerful tool for investigating differential gene expression in earlier and later gestational fetal skins. This technology validates that the mechanism of fetal scarless healing is very complicate and the change of many gene expressions is associated with fetal scarless healing.

An NIR photothermal-responsive hybrid hydrogel for enhanced wound healing

Moderately regulating vascularization and immune microenvironment of wound site is necessary to achieve scarless wound healing of the skin.Herein,we have prepared an angiogenesis-promoting and scar-preventing band-aid with a core-shell structure,that consists of MXene-loaded nanofibers(MNFs)as the core and dopamine-hyaluronic acid hydrogel(H)as the shell(MNFs@V-H@DA)to encapsulate a growth factor(vascular endothelial growth factor,VEGF,abbreviated as V)and H2S donor(diallyl trisulfide,DATS,abbreviated as DA).The continuous release of DA from this system produced H2S,which would successfully induce macrophages to polarize into M2-lile phenotype,regulating the immune microenvironment and inhibiting an excessive inflammatory response at the wound sites.It is conducive to the proliferation of skin cells,facilitating the wound healing.In addition,an appropriate amount of VEGF can be released from the MXene nanofibrous skeleton by adjusting the time of near-infrared(NIR)light exposure,preventing excessive neovascularization and extracellular matrix deposition at the wound sites.Collectively,this NIR photothermal-responsive band-aid achieved scarless wound healing through gradient-controlled vascularization and a related immune sequential reaction of damaged skin tissue.