Intelligent Vascularized 3D/4D/5D/6D‑Printed Tissue Scaffolds

Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D printing.It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds.Herein,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue.Additionally,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds.Finally,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.

3D-Printed Scaffolds Promote Angiogenesis by Recruiting Antigen-Specific T Cells

The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary functions.Inspired by the angiogenesis promotion effect of humoral immune response,we covalently combined mesoporous silica micro rod(MSR)/polyethyleneimine(PEI)/ovalbumin(OVA)self-assembled vaccines with 3D-printed calcium phosphate cement(CPC)scaffolds for local antigen-specific immune response activation.With the response activated,antigen-specific CD4+T helper2(Th2)cells can be recruited to promote early angiogenesis.The silicon(Si)ions from MSRs can accelerate osteogenesis,with an adequate blood supply being provided.At room temperature,scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste,which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid(OHA)inside.Sustained release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine carrier.The vaccine-loaded scaffolds effectively recruited and activated dendritic cells(DCs)for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.When embedded subcutaneously in vivo,the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigenspecific T cells to promote angiogenesis in and around the scaffold.Furthermore,the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized bone.This method may provide a novel concept for patient-specific implant design for angiogenesis promotion.

Biomaterial Scaffolds for Improving Vascularization During Skin Flap Regeneration

Over the past few decades,biomaterials have made rapid advances in tissue engineering.In particular,there have been several studies on vascularization during skin flap regeneration for plastic surgery.From the perspective of function,the biomaterials used to improve the vascularization of skin flaps are primarily classified into two types:(1)electrospun nanofibrous membranes as porous scaffolds,and(2)hydrogels as cell or cytokine carriers.Based on their source,various natural,synthetic,and semi-synthetic biomaterials have been developed with respective characteristics.For the ischemic environment of the flap tissue,the therapeutic effect of the combination of biomaterials was better than that of drugs,cytokines,and cells alone.Biomaterials could improve cell migration,prolong the efficacy of cytokines,and provide an advantageous survival environment to transplanted cells.

Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron regeneration and the glial scar formation.Herein,we apply extracellular vesicles(EVs)secreted by M2 microglia to improve the differentiation of neural stem cells(NSCs)at the injured site,and simultaneously modify them with the injured vascular targeting peptide(DA7R)and the stem cell recruiting factor(SDF-1)on their surface via copper-free click chemistry to recruit NSCs,inducing their neuronal differentiation,and serving as the nanocarriers at the injured site(Dual-EV).Results prove that the Dual-EV could target human umbilical vascular endothelial cells(HUVECs),recruit NSCs,and promote the neuronal differentiation of NSCs in vitro.Furthermore,10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis,and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs,miR30b-3p,miR-222-3p,miR-129-5p,and miR-155-5p may exert effect of inducing NSC to differentiate into neurons.In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice,potentiate NSCs recruitment,and increase neurogenesis.This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells,and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Regulated macrophage immune microenvironment in 3D printed scaffolds for bone tumor postoperative treatment

The 3D printing technique is suitable for patient-specific implant preparation for bone repair after bone tumor resection.However,improving the survival rate due to tumor recurrence remains a challenge for implants.The macrophage polarization induction to M2-type tumor-associated macrophages(TAMs)by the tumor microenvironment is a key factor of immunosuppression and tumor recurrence.In this study,a regenerative scaffold regulating the macrophage immune microenvironment and promoting bone regeneration in a dual-stage process for the postoperative treatment of bone tumors was constructed by binding a colony-stimulating factor 1 receptor(CSF-1R)inhibitor GW2580 onto in situ cosslinked hydroxybutylchitosan(HBC)/oxidized chondroitin sulfate(OCS)hydrogel layer covering a 3D printed calcium phosphate scaffold based on electrostatic interaction.The hydrogel layer on scaffold surface not only supplied abundant sulfonic acid groups for stable loading of the inhibitor,but also acted as the cover mask protecting the bone repair part from exposure to unhealthy growth factors in the microenvironment at the early treatment stage.With local prolonged release of inhibitor being realized via the functional material design,CSF-1R,the main pathway that induces polarization of TAMs,can be efficiently blocked,thus regulating the immunosuppressive microenvironment and inhibiting tumor development at a low therapeutic dose.At the later stage of treatment,calcium phosphate component of the scaffold can facilitate the repair of bone defects caused by tumor excision.In conclusion,the difunctional 3D printed bone repair scaffold regulating immune microenvironment in stages proposed a novel approach for bone tumor postoperative treatment.

“Genetic scissors”CRISPR/Cas9 genome editing cutting-edge biocarrier technology for bone and cartilage repair

CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability,low cost and convenient operation,becoming an efficient and indispensable tool in biological research.As a disruptive technique,CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as well.This review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair,illustrates its mechanism for promoting osteogenesis and chondrogenesis,and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.

Targeted regulation of neuroinflammation via nanobiosignaler for repairing the central nerve system injuries

Neuroinflammation,commonly associated with various central nervous system(CNS)diseases such as postoperative cognitive dysfunction(POCD),is primarily mediated by the disruption of biological signals in microglia.However,the effective treatment of CNS diseases remains an ongoing challenge as biological signals show limited microglia-targeting effect.In this study,taking advantage of the highly expressed lipoprotein receptor-related protein-1(LRP1)on the microglia,a nanobiosignal delivery system modified by LRP1 high-affinity peptide ligand RAP12(RAP:receptor-associated protein)was constructed to specifically regulate neuroinflammation via targeting microglia.The uptake of the RAP12 modified-nanobiosignaler by microglia increased significantly,indicating its microglia-targeting ability.Both in vitro/vivo studies proved that the“nanobiosignaler”significantly reduced the secretion of pro-inflammatory cytokines,induced specific M2(anti-inflammatory type)microglia differentiation,and remarkably alleviated cognitive function impairment in the mice model when compared with unmodified groups.It was indicated that the“nanobiosignaler”could target microglia to deliver the biological signal and inhibit the excessive activation of microglia.Overall,the cell-targeted biological signal transmission system inspired by“nanobiosignaler”has broad application prospects in the future.

Advances in extracellular vesicle functionalization strategies for tissue regeneration

Extracellular vesicles(EVs)are nano-scale vesicles derived by cell secretion with unique advantages such as promoting cell proliferation,anti-inflammation,promoting blood vessels and regulating cell differentiation,which benefit their wide applications in regenerative medicine.However,the in vivo therapeutic effect of EVs still greatly restricted by several obstacles,including the off-targetability,rapid blood clearance,and undesired release.To address these issues,biomedical engineering techniques are vastly explored.This review summarizes different strategies to enhance EV functions from the perspective of drug loading,modification,and combination of biomaterials,and emphatically introduces the latest developments of functionalized EV-loaded biomaterials in different diseases,including cardio-vascular system diseases,osteochondral disorders,wound healing,nerve injuries.Challenges and future directions of EVs are also discussed.

Regulated extravascular microenvironment via reversible thermosensitive hydrogel for inhibiting calcium influx and vasospasm

Arterial vasospasm after microsurgery can cause severe obstruction of blood flow manifested as low tissue temperature,leading to tissue necrosis.The timely discovery and synchronized treatment become pivotal.In this study,a reversible,intelligent,responsive thermosensitive hydrogel system is constructed employing both the gel–sol transition and the sol–gel transition.The“reversible thermosensitive(RTS)”hydrogel loaded with verapamil hydrochloride is designed to dynamically and continuously regulate the extravascular microenvi-ronment by inhibiting extracellular calcium influx.After accurate implantation and following in situ gelation,the RTS hydrogel reverses to the sol state causing massive drug release to inhibit vasospasm when the tissue tem-perature drops to the predetermined transition temperature.Subsequent restoration of the blood supply allevi-ates further tissue injury.Before the temperature drops,the RTS hydrogel maintains the gel state as a sustained-release reservoir to prevent vasospasm.The inhibition of calcium influx and vasospasm in vitro and in vivo is demonstrated using vascular smooth muscle cells,mice mesenteric arterial rings,and vascular ultrasonic Doppler detection.Subsequent animal experiments demonstrate that RTS hydrogel can promote tissue survival and alleviate tissue injury responding to temperature change.Therefore,this RTS hydrogel holds therapeutic po-tential for diseases requiring timely detection of temperature change.

Living Electrospun Short Fibrous Sponge via Engineered Nanofat for Wound Healing

Living cells and active factors are the two core elements of tissue repair,directly affecting the healing efficiency of damaged tissue.Nanofat(NF)can release living cells,such as adipose-derived stem cells(ADSCs),as well as active growth factors to promote angiogenesis,thus realizing cell-based wound healing.Herein,a novel living electrospun short fibrous sponge is constructed by modifying three-dimensional(3D)bionic short fibers with engineered NF.The uniform distribution of the polydopamine(PDA)modification endows the living sponges with stable mechanical properties,reversible water absorption and excellent adhesion even after repeated compression by an external force and long-term aqueous immersion.Meanwhile,the living electrospun short fibrous sponges with uniform NF modification contain living cells such as ADSCs and active growth factors such as vascular endothelial growth factor(VEGF),which can effectively promote the tube formation of human umbilical vein endothelial cells(HUVECs).In vivo,the living sponges can effectively and continuously act on wounds and act as a bionic living skin to prevent the loss of internal nutrients,creating a comfortable and favorable microenvironment for tissue regeneration and promoting the healing of diabetic wounds.Therefore,living electrospun short fibrous sponges via engineered NF are expected to achieve continuous wound healing with in situ living cells and active factors in injured tissues.

Double‑Layer Nanofibrous Sponge Tube via Electrospun Fiber and Yarn for Promoting Urethral Regeneration

Insufficient bionic performance is a structural obstacle and makes urethral repair unobtainable.To overcome this challenge,we mimicked the urethral matrix and applied two electrospinning techniques to build a double-layer sponge tube of nanofib-ers and nanoyarns.Intriguingly,silk fibroin(SF)and vitamin B5(VitB5)could be introduced to increase the elasticity of the outer layer and reduce the hydrophobicity to further improve mesenchymal cell proliferation.Systematic experiments validated the bionic structure,biocompatibility,and exosome delivery capacity in this scaffold.We achieved scarless urethral repair by delivering the bioactive growth factors from adipose-derived stem cell exosomes by physical absorption.Biological regeneration of the urethra can be accomplished with continuous epithelium in animals.Furthermore,bioinformatics studies revealed that the expression of cell proliferation and fibrotic genes(e.g.,Wnt7a,cfa-miR-574)was responsible for the bio-logical regeneration of the adipose-derived stem cells exosomes(ADSC-exos)by delivering poly l-lactide-co-caprolactone/SF/VitB5 bilayer sponge(PSVBS)via reduced fibrosis gene expression,as well as improved epithelial formation and blood vessel formation.Therefore,the PSVBS design appeared to be an instructive approach for urethral and other tubular organ regeneration.

In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy

In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects,which is heavily dependent on the local conversion or activation of bioinert components.In this work,we applied a phospholipid-mimic artemisinin prodrug(ARP)for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis(RA)lesion.ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug,which can formulate“drug-in-drug”co-delivery liposomes with cargo of partner drugs(e.g.,methotrexate).To further stabilize ARP/methotrexate“drug-in-drug”liposomes(MTX/ARPL)for a long-term intra-articular retention,a liposome-embedded hydrogel nano/microsphere(MTX/ARPL@MS)was prepared.After the local injection,the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously.ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation.Taken together,phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs,which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases.

Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma

Understanding the details of metabolic reprogramming in hepatocellular carcinoma(HCC)is critical to improve stratification for therapy.Both multiomics analysis and cross-cohort validation were performed to investigate the metabolic dysregulation of 562 HCC patients from 4 cohorts.On the basis of the identified dynamic network biomarkers,227 substantial metabolic genes were identified and a total of 343 HCC patients were classified into 4 heterogeneous metabolic clusters with distinct metabolic characteristics:cluster 1,the pyruvate subtype,associated with upregulated pyruvate metabolism;cluster 2,the amino acid subtype,with dysregulated amino acid metabolism as the reference;cluster 3,the mixed subtype,in which lipid metabolism,amino acid metabolism,and glycan metabolism are dysregulated;and cluster 4,the glycolytic subtype,associated with the dysregulated carbohydrate metabolism.These 4 clusters showed distinct prognoses,clinical characteristics and immune cell infiltrations,which was further validated by genomic alterations,transcriptomics,metabolomics,and immune cell profiles in the other 3 independent cohorts.Besides,the sensitivity of different clusters to metabolic inhibitors varied depending on their metabolic features.Importantly,cluster 2 is rich in immune cells in tumor tissues,especially programmed cell death protein 1(PD-1)-expressing cells,which may be due to the tryptophan metabolism disorders,and potentially benefiting more from PD-1 treatment.In conclusion,our results suggest the metabolic heterogeneity of HCC and make it possible to treat HCC patients precisely and effectively on specific metabolic characteristics.

Engineered extracellular vesicles for ischemic stroke treatment

Dear Editor,Nanotechnology-based therapeutic strategies have been proven effective in diseases including cancer,infection,inflammation,etc.1 However,the application of nanotechnology is greatly restricted in the treatment of central nervous system(CNS)disorders due to physiological CNS barriers.For example,the blood-brain barrier(BBB)can be the“Maginot line”for pharmacologically active molecules,blocking them out of the CNS.

Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis

The occurrence of osteoarthritis(OA)is highly associated with the reduced lubrication property of the joint,where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism.In this study,bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel,we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment.Particularly,the lubricating microspheres(GelMA@DMA-MPC)were fabricated by dip coating a self-adhesive polymer(DMA-MPC,synthesized by free radical copolymerization)on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres(GelMA,prepared via microfluidic technology),and encapsulated with an anti-inflammatory drug of diclofenac sodium(DS)to achieve the dual-functional performance.The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres.In addition,the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model,and the biological tests including qRT-PCR,immunofluorescence staining assay,X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA.In summary,the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release,therefore representing a facile and promising technique for the treatment of OA.

Functional Electrospun Fibers for Local Therapy of Cancer

Despite great efforts and advancement in the treatment of cancer,tumor recurrence and metastasis remain significant challenges and demand novel therapy strategies.Recently,advances in biomaterials and drug delivery systems have facilitated the development of the local therapy of cancer,among which electrospun nanofibrous scaffolds show great promise owing to their porous structure,relatively large surface area,high drug loading capacity,similarity with the native extracellular matrix,and possibility of the combination of various therapies.Here,we review this rapidly developing field of electrospun nanofibrous scaffolds as a drug delivery system for cancer local therapy,in particular addressing stimuli-responsive drug release,as well as its combination with stem cell and immune therapy.Challenges and future perspectives are also discussed.

Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy

Surgery is the final choice for most patients with intervertebral disc degeneration(IDD).Operation-caused trauma will cause inflammation in the intervertebral disc.Serious inflammation will cause tissue defects and induce tissue degeneration,IDD recurrence and the occurrence of other diseases.Therefore,we proposed a scheme to treat recurrence after discectomy by inhibiting inflammation with an aspirin(ASP)-loaded hydrogel to restore the mechanical stability of the spine and relieve local inflammation.ASP-liposomes(ASP-Lips)were incorporated into a photocrosslinkable gelatin-methacryloyl(GelMA)via mixing.This material can effectively alleviate inflammation by inhibiting the release of high mobility group box 1(HMGB1)from the nucleus to the cytoplasm.We further assessed the expression of inflammatory cytokines,such as interleukin 6(IL-6)and tumor necrosis factor-α(TNF-α),and degeneration-related factors,such as type II collagen(COL-2),Aggrecan,matrix metallopeptidases-3(MMP-3),MMP-13,a disintegrin and metalloproteinase with thrombospondin motifs-4(ADAMTS-4)and ADAMTS-5 in rat nucleus pulpous cells.The level of IDD was analyzed through H&E,safranin-O staining and immunohistochemistry in rabbit samples.In vitro,we found that ASP-Lip@GelMA treatment significantly decreased inflammatory cytokines,MMP-3 and-13,and ADAMTS-4 and-5 and up-regulated COL-2 and Aggrecan via the inhibited release of HMGB-1 from the nucleus.In vivo,ASP-Lip@GelMA can effectively inhibit inflammation of local tissue after disc surgery and fill local tissue defects.This composite hydrogel system is a promising way to treat the recurrence of IDD after surgery without persistent complications.

Lotus seedpod-inspired internal vascularized 3D printed scaffold for bone tissue repair

In the field of bone defect repair,3D printed scaffolds have the characteristics of personalized customization and accurate internal structure.However,how to construct a well-structured vascular network quickly and effectively inside the scaffold is essential for bone repair after transplantation.Herein,inspired by the unique biological structure of“lotus seedpod”,hydrogel microspheres encapsulating deferoxamine(DFO)liposomes were prepared through microfluidic technology as“lotus seeds”,and skillfully combined with a three-dimensional(3D)printed bioceramic scaffold with biomimetic“lotus”biological structure which can internally grow blood vessels.In this composite scaffold system,DFO was effectively released by 36%in the first 6 h,which was conducive to promote the growth of blood vessels inside the scaffold quickly.In the following 7 days,the release rate of DFO reached 69%,which was fundamental in the formation of blood vessels inside the scaffold as well as osteogenic differentiation of bone mesenchymal stem cells(BMSCs).It was confirmed that the composite scaffold could significantly promote the human umbilical vein endothelial cells(HUVECs)to form the vascular morphology within 6 h in vitro.In vivo,the composite scaffold increased the expression of vascularization and osteogenic related proteins Hif1-α,CD31,OPN,and OCN in the rat femoral defect model,significantly cutting down the time of bone repair.To sum up,this“lotus seedpod”inspired porous bioceramic 3D printed scaffold with internal vascularization functionality has broad application prospects in the future.

Shear-responsive boundary-lubricated hydrogels attenuate osteoarthritis

Lipid-based boundary layers formed on liposome-containing hydrogels can facilitate lubrication.However,these boundary layers can be damaged by shear,resulting in decreased lubrication.Here,a shear-responsive boundary-lubricated drug-loaded hydrogel is created by incorporating celecoxib(CLX)-loaded liposomes within dynamic covalent bond-based hyaluronic acid(HA)hydrogels(CLX@Lipo@HA-gel).The dynamic cross-linked network enables the hydrogel to get restructured in response to shear,and the HA matrix allows the accumulation of internal liposome microreservoirs on the sliding surfaces,which results in the formation of boundary layers to provide stable lubrication.Moreover,hydration shells formed surrounding the hydrogel can retard the degradation process,thus helping in sustaining lubrication.Furthermore,in vitro and in vivo experiments found that CLX@Lipo@HA-gels can maintain anabolic-catabolic balance,alleviate cartilage wear,and attenuate osteoarthritis progression by delivering CLX and shear-responsive boundary lubrication.Overall,CLX@Lipo@HA-gels can serve as shear-responsive boundary lubricants and drug-delivery vehicles to alleviate friction-related diseases like osteoarthritis.

Hydration-Enhanced Lubricating Electrospun Nanofibrous Membranes Prevent Tissue Adhesion

Lubrication is the key to efficient function of human tissues and has significant impact on the comfort level.However,the construction of a lubricating nanofibrous membrane has not been reported as yet,especially using a one-step surface modification method.Here,bioinspired by the superlubrication mechanism of articular cartilage,we successfully construct hydration-enhanced lubricating nanofibers via one-step in situ grafting of a copolymer synthesized by dopamine methacrylamide(DMA)and 2-methacryloyloxyethyl phosphorylcholine(MPC)onto electrospun polycaprolactone(PCL)nanofibers.The zwitterionic MPC structure provides the nanofiber surface with hydration lubrication behavior.The coefficient of friction(COF)of the lubricating nanofibrous membrane decreases significantly and is approximately 65%less than that of pure PCL nanofibers,which are easily worn out under friction regardless of hydration.The lubricating nanofibers,however,show favorable wear-resistance performance.Besides,they possess a strong antiadhesion ability of fibroblasts compared with pure PCL nanofibers.The cell density decreases approximately 9-fold,and the cell area decreases approximately 12 times on day 7.Furthermore,the in vivo antitendon adhesion data reveals that the lubricating nanofiber group has a significantly lower adhesion score and a better antitissue adhesion.Altogether,our developed hydration-enhanced lubricating nanofibers show promising applications in the biomedical field such as antiadhesive membranes.