Delayed or non-healing of diabetic wounds is a significant complication,often attributed to high glucose-induced M1 macrophage accumulation,impaired angiogenesis,and reactive oxygen species(ROS)buildup.Addressing this...Delayed or non-healing of diabetic wounds is a significant complication,often attributed to high glucose-induced M1 macrophage accumulation,impaired angiogenesis,and reactive oxygen species(ROS)buildup.Addressing this,we introduced a strontium polyphenol network microneedle patch(SrC-MPNs@MN-PP)for percutaneous drug delivery.This patch,formulated with polymer poly(γ-glutamic acid)(γ-PGA)and epsilon-poly-l-lysine(ε-PLL),incorporates strontium polyphenol networks(SrC-MPNs).The release of chlorogenic acid(CGA)from SrC-MPNs not only neutralizes ROS,but strontium ions also foster angiogen-esis.Consequently,SrC-MPNs@MN-PP can ameliorate the diabetic wound microenvironment and expedite healing.展开更多
Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potenti...Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous(SC)and intravenous(IV)administration,but there is a risk of haemorrhage via SC and IV.Thus,microneedle(MN)provides painless and sanitary alternatives to syringes and oral administration.However,the current technological process for the micro mould is complicated and expensive.The micro mould obtained via three-dimensional(3D)printing is expected to save time and cost,as well as provide a diverse range of MNs.Therefore,we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch.The results show that r-hirudin-loaded and hyaluronic acid(HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models.These results indicate that based on 3D printing technology,MNs combined with r-hirudin are expected to achieve diverse customizableMNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.展开更多
Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of tran...Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.展开更多
Microneedles(MNs)with unique three-dimensional stereochemical structures are suitable candidates for tissue fixation and drug delivery.However,existing hydrogel MNs exhibit poor mechanical properties after swelling an...Microneedles(MNs)with unique three-dimensional stereochemical structures are suitable candidates for tissue fixation and drug delivery.However,existing hydrogel MNs exhibit poor mechanical properties after swelling and require complex preparation procedures,impeding their practical application.Hence,we engineered chitosan fiber-reinforced silk fibroin MN patches containing epigallocatechin gallate(SCEMN).A formic acid-calcium chloride system was introduced to fabricate hydrogel MNs with excellent inherent adhesion,and the incorporation of chitosan fiber as a reinforcing material enhanced mechanical strength and viscosity,thereby increasing the physical interlocking with tissue and the ability to maintain shape.The SCEMN with a lower insertion force firmly adhered to porcine skin,with a maximum detachment force of 11.98 N/cm^(2).Additionally,SCEMN has excellent antioxidant and antibacterial properties,facilitates macrophage polarization from M1 to M2,and demonstrates superior performance in vivo for diabetic wound repair compared with the commercial product Tegaderm^(TM).This study represents the first trial of fiber-reinforced hydrogel MNs for robust tissue adhesion.Our findings underscore the significance of this innovative approach for advancing MN technology to enhance tissue adhesion and accel-erate wound healing.展开更多
Diabetes mellitus,an epidemic with a rapidly increasing number of patients,always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization,decreased angiogenesis and increased reactiv...Diabetes mellitus,an epidemic with a rapidly increasing number of patients,always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization,decreased angiogenesis and increased reactive oxygen species(ROS)in the microenvironment.Herein,a poly(lactic-co-glycolic acid)(PLGA)-based microneedle patch loaded with magnesium hydride(MgH_(2))(MN-MgH_(2))is manufactured for defeating diabetic wounds.The application of microneedle patch contributes to the transdermal delivery and the prolonged release of MgH_(2) that can generate hydrogen(H_(2))and magnesium ions(Mg^(2+))after reaction with body fluids.The released H_(2) reduces the production of ROS,transforming the pathological microenvironment induced by diabetes mellitus.Meanwhile,the released Mg^(2+)promotes the polarization of pro-healing M2 macrophages.Consequently,cell proliferation and migration are improved,and angiogenesis and tissue regeneration are enhanced.Such intelligent microneedle patch provides a novel way for accelerating wound healing through steadily preserving and releasing of H_(2) and Mg^(2+)locally and sustainably.展开更多
In cutaneous cosmetology surgery,local injection or coated anesthetics are generally used to provide analgesia at the treatment site to achieve painless operation.Due to the barrier of corneum,topical cream may cause ...In cutaneous cosmetology surgery,local injection or coated anesthetics are generally used to provide analgesia at the treatment site to achieve painless operation.Due to the barrier of corneum,topical cream may cause uncertain dosage and delayed analgesia.Local injection has problems such as pain,infection,and misoperation.Therefore,it is necessary to develop a painless and rapid administration method for local anesthesia.Here,a lidocaine/hyaluronic acid bubble microneedle patch(Lido/HA bMNP)was prepared for rapid drug delivery and efficient analgesia.The bubble structure between microneedles(MNs)and the backing layer allowed the MNs to efficiently penetrate into the skin and remove from the backing layer under shear force to rapidly complete the administration.Drugs were quickly released with the dissolution of HA within 15 s,which immediately played an analgesic effect and lasted for 1 h.Lido/HA bMNP could deliver precise doses to the skin in an extremely short time,which had the advantages of convenient operation,high biosafety,rapid onset of analgesia,and reasonable pain relief time.This patch provided an alternative way for local anesthesia and it was a promising transdermal drug delivery method for the realization of high quality and efficiency“painless medical beauty”.展开更多
Hypertrophic scar(HS)is a plaque fibrous and indurated dermal lesion that may cause physical,psychological,and cosmetic challenges for patients.Intralesional injection of triamcinolone acetonide(TA)is commonly used in...Hypertrophic scar(HS)is a plaque fibrous and indurated dermal lesion that may cause physical,psychological,and cosmetic challenges for patients.Intralesional injection of triamcinolone acetonide(TA)is commonly used in clinical practice,which cause unbearable pain and uneven drug delivery within HS tissue.Herein,we developed a paper battery powered iontophoresis-driven microneedles patch(PBIMNP)for self-management of HS.The high integration of PBIMNP was achieved by incorporating a paper battery as the power source for iontophoresis.The transdermal drug delivery strategy of PBIMNP combined microneedles and iontophoresis techniques,involving“pressing and poking,phase transformation,and diffusion and iontophoresis”,which can actively deliver 90.19%drug into the HS tissue with excellent in vitro drug permeation performance.PBIMNP administration effectively reduced the mRNA and protein levels,leading to a decrease in the expression of TGF-β1 and Col I associated with HS formation,demonstrating its efficacy in HS treatment.The microneedles and wearable design endow the PBIMNP as a highly promising platform for self-administration on HS treatment.展开更多
Cisplatin resistance in tumors is closely linked to the upregulation of the nucleotide excision repair(NER)pathway,particularly the excision repair cross-complementing-1–xeroderma pigmentosum complementation group F(...Cisplatin resistance in tumors is closely linked to the upregulation of the nucleotide excision repair(NER)pathway,particularly the excision repair cross-complementing-1–xeroderma pigmentosum complementation group F(ERCC1–XPF)complex.Here,we present a tumor-responsive microneedle(MN)patch platform for localized co-delivery of a NER-targeting proteolysis-targeting chimera(PROTAC)degrader(NERiP)and a Pt(Ⅳ)prodrug to overcome this resistance.This platform integrates pH-responsive PEG-PAE micelles,which co-encapsulate NERiP and Pt(Ⅳ),into dissolvable methacrylated hyaluronic acid microneedles for transdermal administration.Upon insertion into tumor-bearing skin,the MNs enable sustained and localized release of the micelles.In the mildly acidic tumor microenvironment,the micelles undergo surface charge reversal and rapid disassembly,resulting in synchronized release of both agents.This spatiotemporally coordinated delivery effectively downregulates ERCC1–XPF proteins and promotes platinum-induced DNA crosslinking,thereby enhancing apoptosis in cisplatin-resistant A375/CDDP melanoma cells.In vivo studies demonstrate that MN-mediated delivery significantly improves intratumoral drug accumulation and deep tissue penetration,achieving a tumor growth inhibition rate of 79.9%with minimal systemic toxicity.By combining tumor microenvironment-responsive release with minimally invasive localized delivery,this strategy enables synergistic NER pathway suppression and platinum-mediated genotoxicity.Furthermore,the MN platform ensures deep intratumoral distribution and prolonged retention,offering a promising therapeutic approach to address platinum resistance in solid tumors.展开更多
Delayed wound healing in diabetes is a global challenge,and the development of related drugs is a clinical problem to be solved.In this study,purpurolide C(PC),a small-molecule secondary metabolite of the endophytic f...Delayed wound healing in diabetes is a global challenge,and the development of related drugs is a clinical problem to be solved.In this study,purpurolide C(PC),a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum,was found to promote diabetic wound healing.To investigate the key regulation targets of PC,in vitro RNA-seq,molecular docking calcula-tions,TLR4-MD2 dimerization SDS-PAGE detection,and surface plasmon resonance(SPR)were per-formed,indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation.Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing.Furthermore,a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC(PC@MLIP MN)was developed,which overcame the poor water solubility and weak skin permeability of PC,so that successfully punctured the skin and delivered PC to local tissues,and accurately regulated macrophage polarization in diabetic wound management.Overall,PC is an anti-inflammatory small molecule compound with a well-defined structure and dualtarget regulation,and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.展开更多
基金supported by the National Natural Science Foundation of China(No.31971271)The Natural Science Foundation of Fujian Province of China(No.2022J01794)The Science and Technology Plan Project of Quanzhou(No.2021N033S).
文摘Delayed or non-healing of diabetic wounds is a significant complication,often attributed to high glucose-induced M1 macrophage accumulation,impaired angiogenesis,and reactive oxygen species(ROS)buildup.Addressing this,we introduced a strontium polyphenol network microneedle patch(SrC-MPNs@MN-PP)for percutaneous drug delivery.This patch,formulated with polymer poly(γ-glutamic acid)(γ-PGA)and epsilon-poly-l-lysine(ε-PLL),incorporates strontium polyphenol networks(SrC-MPNs).The release of chlorogenic acid(CGA)from SrC-MPNs not only neutralizes ROS,but strontium ions also foster angiogen-esis.Consequently,SrC-MPNs@MN-PP can ameliorate the diabetic wound microenvironment and expedite healing.
基金supported by the National Natural Science Foundation of China (NSFC 81902995)the project funded by China Postdoctoral Science Foundation (2018M641936)
文摘Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous(SC)and intravenous(IV)administration,but there is a risk of haemorrhage via SC and IV.Thus,microneedle(MN)provides painless and sanitary alternatives to syringes and oral administration.However,the current technological process for the micro mould is complicated and expensive.The micro mould obtained via three-dimensional(3D)printing is expected to save time and cost,as well as provide a diverse range of MNs.Therefore,we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch.The results show that r-hirudin-loaded and hyaluronic acid(HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models.These results indicate that based on 3D printing technology,MNs combined with r-hirudin are expected to achieve diverse customizableMNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.
基金supported by the Joint Funds of National Natural Science Foundation of China(No.U22A20162)the Natural Science Foundation of Hebei Province of China(No.C2021202002)+1 种基金the National Natural Science Foundation of China(No.52271245),the Natural Science Foundation of Tianjin(No.21JCQNJC01280)the financial support from the Danish Council for Independent Research(9040-00219B),European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement ENSIGN(Project ID:101086226),L4DNANO(Project ID:101086227).
文摘Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.
基金supported by the National Natural Science Foundation of China(No.51803171)the Fundamental Research Funds for Central Universities(No.SWU-XDPY22010).
文摘Microneedles(MNs)with unique three-dimensional stereochemical structures are suitable candidates for tissue fixation and drug delivery.However,existing hydrogel MNs exhibit poor mechanical properties after swelling and require complex preparation procedures,impeding their practical application.Hence,we engineered chitosan fiber-reinforced silk fibroin MN patches containing epigallocatechin gallate(SCEMN).A formic acid-calcium chloride system was introduced to fabricate hydrogel MNs with excellent inherent adhesion,and the incorporation of chitosan fiber as a reinforcing material enhanced mechanical strength and viscosity,thereby increasing the physical interlocking with tissue and the ability to maintain shape.The SCEMN with a lower insertion force firmly adhered to porcine skin,with a maximum detachment force of 11.98 N/cm^(2).Additionally,SCEMN has excellent antioxidant and antibacterial properties,facilitates macrophage polarization from M1 to M2,and demonstrates superior performance in vivo for diabetic wound repair compared with the commercial product Tegaderm^(TM).This study represents the first trial of fiber-reinforced hydrogel MNs for robust tissue adhesion.Our findings underscore the significance of this innovative approach for advancing MN technology to enhance tissue adhesion and accel-erate wound healing.
文摘Diabetes mellitus,an epidemic with a rapidly increasing number of patients,always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization,decreased angiogenesis and increased reactive oxygen species(ROS)in the microenvironment.Herein,a poly(lactic-co-glycolic acid)(PLGA)-based microneedle patch loaded with magnesium hydride(MgH_(2))(MN-MgH_(2))is manufactured for defeating diabetic wounds.The application of microneedle patch contributes to the transdermal delivery and the prolonged release of MgH_(2) that can generate hydrogen(H_(2))and magnesium ions(Mg^(2+))after reaction with body fluids.The released H_(2) reduces the production of ROS,transforming the pathological microenvironment induced by diabetes mellitus.Meanwhile,the released Mg^(2+)promotes the polarization of pro-healing M2 macrophages.Consequently,cell proliferation and migration are improved,and angiogenesis and tissue regeneration are enhanced.Such intelligent microneedle patch provides a novel way for accelerating wound healing through steadily preserving and releasing of H_(2) and Mg^(2+)locally and sustainably.
基金the National Natural Science Foundation of China(Nos.61875015 and T2125003)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16021101)Beijing Natural Science Foundation(Nos.JQ20038,L212010,and L212046).
文摘In cutaneous cosmetology surgery,local injection or coated anesthetics are generally used to provide analgesia at the treatment site to achieve painless operation.Due to the barrier of corneum,topical cream may cause uncertain dosage and delayed analgesia.Local injection has problems such as pain,infection,and misoperation.Therefore,it is necessary to develop a painless and rapid administration method for local anesthesia.Here,a lidocaine/hyaluronic acid bubble microneedle patch(Lido/HA bMNP)was prepared for rapid drug delivery and efficient analgesia.The bubble structure between microneedles(MNs)and the backing layer allowed the MNs to efficiently penetrate into the skin and remove from the backing layer under shear force to rapidly complete the administration.Drugs were quickly released with the dissolution of HA within 15 s,which immediately played an analgesic effect and lasted for 1 h.Lido/HA bMNP could deliver precise doses to the skin in an extremely short time,which had the advantages of convenient operation,high biosafety,rapid onset of analgesia,and reasonable pain relief time.This patch provided an alternative way for local anesthesia and it was a promising transdermal drug delivery method for the realization of high quality and efficiency“painless medical beauty”.
基金financially supported by the Shenzhen Science and Technology Program(Project No.JCYJ20220818102201003)the National Natural Science Foundation of China(Project No.51975597,52175446,and T2225010)+2 种基金the Natural Science Foundation of Guangdong Province(Project No.2022B1515020011)the Shenzhen Medical Research Fund(Project No.A2302034)the Foundation of Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument(Project No.2020B1212060077).
文摘Hypertrophic scar(HS)is a plaque fibrous and indurated dermal lesion that may cause physical,psychological,and cosmetic challenges for patients.Intralesional injection of triamcinolone acetonide(TA)is commonly used in clinical practice,which cause unbearable pain and uneven drug delivery within HS tissue.Herein,we developed a paper battery powered iontophoresis-driven microneedles patch(PBIMNP)for self-management of HS.The high integration of PBIMNP was achieved by incorporating a paper battery as the power source for iontophoresis.The transdermal drug delivery strategy of PBIMNP combined microneedles and iontophoresis techniques,involving“pressing and poking,phase transformation,and diffusion and iontophoresis”,which can actively deliver 90.19%drug into the HS tissue with excellent in vitro drug permeation performance.PBIMNP administration effectively reduced the mRNA and protein levels,leading to a decrease in the expression of TGF-β1 and Col I associated with HS formation,demonstrating its efficacy in HS treatment.The microneedles and wearable design endow the PBIMNP as a highly promising platform for self-administration on HS treatment.
基金financially supported by the National Natural Science Foundation of China(No.32000996)the Key Program of Nanozyme Laboratory in Zhongyuan(No.NLZ-KP2024NIC02)the Grant for International Joint Research Project of the Institute of Medical Science,the University of Tokyo(No.Extension-2019-K3005).
文摘Cisplatin resistance in tumors is closely linked to the upregulation of the nucleotide excision repair(NER)pathway,particularly the excision repair cross-complementing-1–xeroderma pigmentosum complementation group F(ERCC1–XPF)complex.Here,we present a tumor-responsive microneedle(MN)patch platform for localized co-delivery of a NER-targeting proteolysis-targeting chimera(PROTAC)degrader(NERiP)and a Pt(Ⅳ)prodrug to overcome this resistance.This platform integrates pH-responsive PEG-PAE micelles,which co-encapsulate NERiP and Pt(Ⅳ),into dissolvable methacrylated hyaluronic acid microneedles for transdermal administration.Upon insertion into tumor-bearing skin,the MNs enable sustained and localized release of the micelles.In the mildly acidic tumor microenvironment,the micelles undergo surface charge reversal and rapid disassembly,resulting in synchronized release of both agents.This spatiotemporally coordinated delivery effectively downregulates ERCC1–XPF proteins and promotes platinum-induced DNA crosslinking,thereby enhancing apoptosis in cisplatin-resistant A375/CDDP melanoma cells.In vivo studies demonstrate that MN-mediated delivery significantly improves intratumoral drug accumulation and deep tissue penetration,achieving a tumor growth inhibition rate of 79.9%with minimal systemic toxicity.By combining tumor microenvironment-responsive release with minimally invasive localized delivery,this strategy enables synergistic NER pathway suppression and platinum-mediated genotoxicity.Furthermore,the MN platform ensures deep intratumoral distribution and prolonged retention,offering a promising therapeutic approach to address platinum resistance in solid tumors.
基金supported by grants from National Key R&D Program of China(Grant NO.2022YFC2504200 to Yi Liu)the National Nature Science Foundation of China(81991504 and 81974149 to Yi Liu,82073978 to Sheng Lin,82201053 to Yitong Liu,81803397 to Guiyang Xia,82122015 to Junji Xu)+6 种基金the Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202202 to Yi Liu,China)the Innovation Foundation of Beijing Stomatological Hospital,Capital Medical University(21-09-18 to Lijia Guo,China)the Beijing Stomatological Hospital,Capital Medical University Young Scientist Program(YSP202105 to Yitong Liu,China)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX202121 to Yi Liu,China)Beijing Municipal Administration of Hospitals'Ascent Plan(DFL20181501 to Yi Liu,China)Beijing Municipal Administration of Hospitals'Youth Programme(QML20181501 to Lijia Guo,QML20231506 to Yitong Liu,China)Beijing Municipal Administration of Hospitals Incubating Program(PX2023054 to Lijia Guo,China).
文摘Delayed wound healing in diabetes is a global challenge,and the development of related drugs is a clinical problem to be solved.In this study,purpurolide C(PC),a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum,was found to promote diabetic wound healing.To investigate the key regulation targets of PC,in vitro RNA-seq,molecular docking calcula-tions,TLR4-MD2 dimerization SDS-PAGE detection,and surface plasmon resonance(SPR)were per-formed,indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation.Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing.Furthermore,a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC(PC@MLIP MN)was developed,which overcame the poor water solubility and weak skin permeability of PC,so that successfully punctured the skin and delivered PC to local tissues,and accurately regulated macrophage polarization in diabetic wound management.Overall,PC is an anti-inflammatory small molecule compound with a well-defined structure and dualtarget regulation,and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.
