| Skin wound caused by direct defect and ulcer,the result of Severe trauma,surgical injury and chronic diseases(vascular diseases,diabetes,etc.),has become one of the important diseases in today’s society,and brings about millions of patients in our country who need skin grafting treatment.Meanwhile,with the aging of the population,the incidence of disease-related chronic wound increases year by year,which not only seriously affects the living quality of patients,but also brings heavy medical burden to the society.Autologous skin grafting is still the criterion standard for the treatment of skin defect.Limited by the shortage of donor area and the great pain of surgery,it cannot meet the needs of clinical treatment.At present,there are three main methods to treat skin wound and defects: wound dressings,artificial skin substitutes and wound intervention agents.Although wound dressings and artificial skin substitutes can close and protect wound in time,compared with traditional gauze dressings,they cannot aim to pathogenesis of skin wound,leaving unsatisfactory therapeutic effect.In addition,the actual difficulties of wound dressing change in clinical practice make the healing process actually in a state of “black box”.In most cases,only the personal experience of physician can be relied on to judge the progress of wound subjectively and blindly give intervention measures.Therefore,it is urgent to develop a new wound treatment system that can not only accelerate wound healing,but also monitor wound state in real time to reduce patients’ pain of dressing change,and give wound intervention treatment as needed.In this study,we mainly completed three aspects of the work.By integrating the emerging bioelectronics and software,we built a flexible smart temperature sensoring wound system.The device system was designed as Band-Aid shape with double-layer structure,the upper is the flexible temperature sensing layer consisted of temperature sensor,power manager circuit and data processing circuit,and the lower is pro-regeneration collagen-chitosan dermal equivalent.A customized software application,installed into a smartphone to exchange data with sensoring system by BLE4.0,could display and analyze real-time wound status.The system was applied to pig skin wound model to pioneeringly reveal the temperature fluctuation during the whole wound regeneration process.Having considerable relatedness with inflammatory cell infiltration,angiogenesis and wound healing,three main phases of wound temperature fluctuation were found.Furthermore,verified by wound infection model of different healing phase,early warning,at least 20 hours ahead serious infection,would be offered with the help of alarm of customized app.Applying the gene-activated strategy to enhance sustained expression of vascular endothelial growth factor(VEGF),The gene-activated bilayer dermal equivalents(GaBDEs),were fabricated by loading the nano-sized complexes of Lipofectamine2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent.The DNA complexes could release in a sustained manner and showed the effective transfection capacities.A reformative rat model of full-thickness diabetes chronic wound was adopted.Under the treatment of Ga-BDEs,speeding wound healing was observed,which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases,respectively.These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously.Subsequently,the better regeneration outcomes,including deposition of oriented collagen and fast reepithelialization,were achieved.Based on the flexible smart temperature sensoring wound system and the geneactivated bilayer dermal equivalents,the software and hardware are integrated into the smart wound system by adding the uv-responsive hydrogel and the uv-generating device.The sensitivity and stability of temperature monitoring,biological reliability and compatibility,and the ability of releasing FTY720 to regulate macrophage phenotype in response to uv light were verified in vitro.It was also applied to the rat diabetic wound model to monitor the real-time wound temperature fluctuation.The APP installed in the smartphone could provide early warning and controlled release of FTY720 in the hydrogel during the peak of inflammation,so as to regulate the phenotypic transformation of macrophages and effectively accelerate wound healing.In vitro,the correlation of FTY720 may be related to the activation of macrophage STAT3 pathway. |
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