Polyhydroxy structure orchestrates the intrinsic antibacterial property of acrylamide hydrogel as a versatile wound-healing dressing.

Hydrogel is considered as a promising candidate for wound dressing due to its tissue-like flexibility, good mechanical properties and biocompatibility. However, traditional hydrogel dressings often fail to fulfill satisfied mechanical, antibacterial, and biocompatibility properties simultaneously, due to the insufficient intrinsic bactericidal efficacy and the addition of external antimicrobial agents. In this paper, hydroxyl-contained acrylamide monomers, N-Methylolacrylamide (NMA) and N-[Tris (hydroxymethyl)methyl] acrylamide (THMA), are employed to prepare a series of polyacrylamide hydrogel dressings xNMA-yTHMA, where x and y represent the mass fractions of NMA and THMA in the hydrogels. We have elucidated that the abundance of hydroxyl groups determines the antibacterial effect of the hydrogels. Particularly, hydrogel 35NMA-5THMA exhibits excellent mechanical properties, with high tensile strength of 259 kPa and large tensile strain of 1737%. Furthermore, the hydrogel dressing 35NMA-5THMA demonstrates remarkable inherent antibacterial without exogenous antimicrobial agents owing to the existence of abundant hydroxyl groups. Besides, hydrogel dressing 35NMA-5THMA possesses excellent biocompatibility, in view of marginal cytotoxicity, low hemolysis ratio, and negligible inflammatory response and organ toxicity to mice during treatment. Encouragingly, hydrogel 35NMA-5THMA drastically promote the healing of bacteria-infected wound in mice. This study has revealed the importance of polyhydroxyl in the antibacterial efficiency of hydrogels and provided a simplified strategy to design wound healing dressings with translational potential.

Hydrogel dressings for diabetic foot ulcer: A systematic review and meta-analysis.

AIM: To investigate the differences in utility between conventional dressings and hydrogel dressings for the treatment of diabetic foot ulcer (DFU). METHODS: The PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases were systematically searched up to 21 January 2023. Fixed/random-effect models were used to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) for the effect size analysis, with heterogeneity determined by I2 statistics. Subgroup analyses of different classes of hydrogel were also conducted. RESULTS: A total of 15 randomized controlled trials with 872 patients were eligible for the present analysis. Compared with conventional dressings, hydrogel dressings significantly improved the healing rate (OR 4.09, 95% CI 2.83 to 5.91), shortened the healing time (MD -11.38, 95% CI -13.11 to -9.66), enhanced granulation formation (MD -3.60, 95% CI -4.21 to -3.00) and epithelial formation (MD -2.82, 95% CI -3.19 to -2.46), and reduced the incidence of bacterial infection (OR 0.10, 95% CI 0.05 to 0.18). CONCLUSION: The meta-analysis showed that hydrogel dressings are more effective in treating DFU compared with conventional dressings.

ICT-based fluorescent probes for intracellular pH and biological species detection.

Fluorescent probes, typically based on the intramolecular charge transfer (ICT) mechanism, have received considerable research attention in cell detection due to their non-invasiveness, fast response, easy regulation, high sensitivity, and low damage tolerance for in vivo bio-samples. Generally, intracellular pH and biological species such as various gases, metal ions, and anions constitute the foundation of cells and participate in the basic physiological processes, whose abnormal level can lead to poisoning, cardiovascular disease, and cancer in living organisms. Therefore, monitoring of their quantity plays an essential role in understanding the status of organisms and preventing, diagnosing, and treating diseases. In the last decades, remarkable progress has been made in developing ICT probes for the detection of biological elements. In this review, we highlight the recent ICT probes focusing primarily on the detection of intracellular pH, various gases (H2S, CO, H2O2, and NO), metal ions (Cu2+, Hg2+, Pb2+, Zn2+, and Al3+), and anions (ClO-, CN-, SO3 2-, and F-). In addition, we discuss the issues and limitations of ICT-based fluorescent probes for in vivo detection and explore the clinical translational potential and challenges of these materials, providing valuable guidance and insights for the design of fluorescent materials.

Recent Research Progress in Fluorescent Probes for Detection of Amyloid-ß In Vivo.

Alzheimer's disease (AD) is a neurodegenerative disease. Due to its complex pathological mechanism, its etiology is not yet clear. As one of the main pathological markers of AD, amyloid-ß (Aß) plays an important role in the development of AD. The deposition of Aß is not only related to the degeneration of neurons, but also can activate a series of pathological events, including the activation of astrocytes and microglia, the breakdown of the blood-brain barrier, and the change in microcirculation, which is the main cause of brain lesions and death in AD patients. Therefore, the development of efficient and reliable Aß-specific probes is crucial for the early diagnosis and treatment of AD. This paper focuses on reviewing the application of small-molecule fluorescent probes in Aß imaging in vivo in recent years. These probes efficiently map the presence of Aß in vivo, providing a pathway for the early diagnosis of AD and providing enlightenment for the design of Aß-specific probes in the future.

Fluorescent Materials with Excellent Biocompatibility and Their Application in Bio-Sensing, Bio-Imaging.

Fluorescent materials have great potential for use in biomedical applications due to their ease of functionalization and tunable fluorescence color [...].

Three-dimensional bioprinted BMSCs-laden highly adhesive artificial periosteum containing gelatin-dopamine and graphene oxide nanosheets promoting bone defect repair.

The periosteum is a connective tissue membrane adhering to the surface of bone tissue that primarily provides nutrients and regulates osteogenesis during bone development and injury healing. However, building an artificial periosteum with good adhesion properties and satisfactory osteogenesis for bone defect repair remains a challenge, especially using three-dimensional (3D) bioprinting. In this study, dopamine was first grafted onto the molecular chain of gelatin usingN-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride andN-hydroxysuccinimide (NHS) to activate the carboxyl group and produce modified gelatin-dopamine (GelDA). Next, a methacrylated gelatin, methacrylated silk fibroin, GelDA, and graphene oxide nanosheet composite bioink loaded with bone marrow mesenchymal stem cells was prepared and used for bioprinting. The physicochemical properties, biocompatibility, and osteogenic roles of the bioink and 3D bioprinted artificial periosteum were then systematically evaluated. The results showed that the developed bioink showed good thermosensitivity and printability and could be used to build 3D bioprinted artificial periosteum with satisfactory cell viability and high adhesion. Finally, the 3D bioprinted artificial periosteum could effectively enhance osteogenesis bothin vitroandin vivo. Thus, the developed 3D bioprinted artificial periosteum can prompt new bone formation and provides a promising strategy for bone defect repair.

A reactive oxygen species-responsive hydrogel encapsulated with bone marrow derived stem cells promotes repair and regeneration of spinal cord injury.

Spinal cord injury (SCI) is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes, such as excessive reactive oxygen species (ROS) produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment, leading to the widespread apoptosis of the neuron cells, glial and oligodendroctyes. In this study, a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells (BMSCs), which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment. The hydrogel could effectively encapsulate BMSCs, and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS, attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), resulting in a reduced cell apoptosis in the spinal cord tissue. The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation, and improved the neurogenesis of the spinal cord tissue, and thus distinctly enhanced the motor functional recovery of SCI rats. Our work provides a combinational strategy against ROS-mediated oxidative stress, with potential applications not only in SCI, but also in other central nervous system diseases with similar pathological conditions.

A Polymeric Strategy Empowering Vascular Cell Selectivity and Potential Application Superior to Extracellular Matrix Peptides.

Endothelialization of vascular implants plays a vital role in maintaining the long-term vascular patency. In situ endothelialization and re-endothelialization is generally achieved by selectively promoting endothelial cell (EC) adhesion and, meanwhile, suppressing smooth muscle cell (SMC) adhesion. Currently, such EC versus SMC selectivity is achieved and extensively used in vascular-related biomaterials utilizing extracellular-matrix-derived EC-selective peptides, dominantly REDV and YIGSR. Nevertheless, the application of EC-selective peptides is limited due to their easy proteolysis, time-consuming synthesis, and expensiveness. To address these limitations, a polymeric strategy in designing and finding EC-selective biomaterials using amphiphilic ß-peptide polymers by tuning serum protein adsorption is reported. The optimal ß-peptide polymer displays EC versus SMC selectivity even superior to EC-selective REDV peptide regarding cell adhesion, proliferation, and migration of ECs versus SMCs. Study of the mechanism indicates that surface adsorption of bovine serum albumin, an abundant and anti-adhesive serum protein, plays a critical role in the ECs versus SMCs selectivity of ß-peptide polymer. In addition, surface modification of the optimal ß-peptide polymer effectively promotes the endothelialization of vascular implants and inhibits intimal hyperplasia. This study provides an alternative strategy in designing and finding EC-selective biomaterials, implying great potential in the vascular-related biomaterial study and application.

Fluorescence Enhancement of Dicyanomethylene-4H-Pyran Derivatives in Solid State for Visualization of Latent Fingerprints.

The efficient development of latent fingerprint (LFP) is attractively important for criminal investigation. The low-cost and high-contrast developer is still a challenge. In this study, we designed and synthesized dicyanomethylene-4H-pyran (DCM) derivatives PZ-DCM and Boc-PZ-DCM by introducing of large steric hindrance group Boc, the solid-state fluorescence of DCM derivatives was greatly enhanced. The low-cost fluorescent LFP developers were prepared by blending with different proportion of montmorillonite (MMT). As a result, clear and high contrast fingerprint patterns were obtained with dusting method by the developer with 3% content of Boc-PZ-DCM. Furthermore, we employed the developer with 3% content of Boc-PZ-DCM to develop the sweat latent fingerprints on different substrates by powder dusting, and collected clear fingerprint patterns, indicating that the developer is universal. In a word, the Boc-PZ-DCM/MMT powder is a promising candidate for LFP developer.

Multifunctional elastomer cardiac patches for preventing left ventricle remodeling after myocardial infarction in vivo.

Myocardial infarction (MI) is still a major cause of mortality and morbidity worldwide. Elastomer cardiac patches have shown great potential in preventing left ventricle (LV) remodeling post-MI by providing mechanical support to the infarcted myocardium. Improved therapeutic outcomes are expected by mediating pathological processes in the necrosis phase, inflammation phase, and fibrosis phase, through orchestrated biological and mechanical treatments. In this study, a mechanically robust multifunctional cardiac patch integrating reactive oxygen species (ROS)-scavenging, anti-inflammatory, and pro-angiogenic capabilities was developed to realize the integrative strategy. An elastomeric polyurethane (PFTU) containing ROS-sensitive poly (thioketal) (PTK) and unsaturated poly (propylene fumarate) (PPF) segments was synthesized, which was further clicked with pro-angiogenic Arg-Glu-Asp-Val (REDV) peptides to obtain PFTU-g-REDV (PR), and was formulated into a macroporous patch containing rosuvastatin (PRR). The mechanical support and multifunctional effects of the patch were confirmed in a rat MI model in vivo compared to the patches with only mechanical support, leading to reduced cell apoptosis, suppressed local inflammatory response, alleviated fibrosis, and induced angiogenesis. The cardiac functions and LV morphology were also well maintained. These results demonstrate the advantages of the integrated and orchestrated treatment strategy in MI therapy.

Micropatterns and peptide gradient on the inner surface of a guidance conduit synergistically promotes nerve regeneration in vivo.

Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo. However, they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far. In this study, a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly (D,L-lactide-co-caprolactone) (PLCL) guidance conduit and its advantages in regeneration of peripheral nerve in vivo. After linear ridges/grooves of 20/40 µm in width are created on the PLCL film, its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups, which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde. The Schwann cells are better aligned along with the stripes, and show a faster migration rate toward the region of higher peptide density. Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate, function recovery and microstructures, and reduction of fibrosis in muscle tissues. Moreover, this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization in vivo.

Macrophage membrane-functionalized nanofibrous mats and their immunomodulatory effects on macrophage polarization.

Immunomodulation is an important phenomenon in the normal mammalian host response toward an injury, and plays a critical role in tissue regeneration and regenerative medicine. Different phenotypes of macrophages show an array of activation states compassing pro-inflammatory to pro-alleviating cells, which are the critical players to modulate immune response and tissue regeneration. In this study, macrophage membranes of different phenotypes (macrophages (M0), classically activated macrophages (M1) and alternatively activated macrophages (M2)) were coated onto poly-ε-caprolactone (PCL) nanofibers to acquire exterior surface proteins and similar functions of the natural membranes. In vitro results unveiled that these nanofibers, especially the M2-PCL nanofibers, can suppress the activities of inflammatory markers such as TNF-α and IL-1ß, and stimulate anti-inflammatory markers such as Arg-1, IL-10 and TGF-ß. In a C57BL/6 mouse model, the macrophage membrane-coated nanofibers, especially the M2-PCL nanofibers, displayed minimal cellular infiltration and low collagen deposition, increased anti-inflammatory CD206 and decreased inflammatory CD86 levels. The M2-PCL nanofibers most effectively neutralized inflammatory chemokines, regulated the expression of inflammation-associated genes as well as anti-inflammatory genes, and showed strong immunomodulatory effects than the PCL, M0-PCL and M1-PCL nanofibers. STATEMENT OF SIGNIFICANCE: Different types of macrophage membrane-functionalized PCL nanofibers were successfully prepared and well characterized. They inherited the surface proteins imitating the source macrophages, and played an important role in limiting cellular infiltration and collagen deposition. These different macrophages and their membrane-coated nanofibers (M0-PCL, M1-PCL and M2-PCL) behaved like their respective source cells. The M2 mimicking M2-PCL nanofibers effectively polarized macrophages to M2 phenotype and decreased the expression of inflammation-associated chemokines and promoted the anti-inflammation in vitro and in vivo, which is critical for tissue regeneration. The mice implanted with the bio-mimicking M2-PCL nanofibers effectively inhibited toll like receptors signaling induced NF-kB and IRF-5 and their target genes such as Edn-1, IL-6, iNOS, TNF-α, etc. compared to the PCL, and M0-PCL and M1-PCL macrophage membrane-coated nanofibers.

Micropatterned Poly(D,L-Lactide-Co-Caprolactone) Conduits With KHI-Peptide and NGF Promote Peripheral Nerve Repair After Severe Traction Injury.

Severe traction injuries after stretch to peripheral nerves are common and challenging to repair. The nerve guidance conduits (NGCs) are promising in the regeneration and functional recovery after nerve injuries. To enhance the repair of severe nerve traction injuries, in this study KHIFSDDSSE (KHI) peptides were grafted on a porous and micropatterned poly(D,L-lactide-co-caprolactone) (PLCL) film (MPLCL), which was further loaded with a nerve growth factor (NGF). The adhesion number of Schwann cells (SCs), ratio of length/width (L/W), and percentage of elongated SCs were significantly higher in the MPLCL-peptide group and MPLCL-peptide-NGF group compared with those in the PLCL group in vitro. The electromyography (EMG) and morphological changes of the nerve after severe traction injury were improved significantly in the MPLCL-peptide group and MPLCL-peptide-NGF group compared with those in the PLCL group in vivo. Hence, the NGCs featured with both bioactive factors (KHI peptides and NGF) and physical topography (parallelly linear micropatterns) have synergistic effect on nerve reinnervation after severe traction injuries.

Large fuzzy biodegradable polyester microspheres with dopamine deposition enhance cell adhesion and bone regeneration in vivo.

The biodegradable polymer microparticles with different surface morphology and chemical compositions may influence significantly the behaviors of cells, and thereby further the performance of tissue regeneration in vivo. In this study, multi-stage hierarchical textures of poly(D,L-lactic-co-glycolide) (PLGA)/PLGA-b-PEG (poly(ethylene glycol)) microspheres with a diameter as large as 50-100 µm are fabricated based on interfacial instability of an emulsion. The obtained fuzzy structures on the microspheres are sensitive to annealing, which are changed gradually to a smooth one after treatment at 37 °C for 6 d or 80 °C for 1 h. The surface microstructures that are chemically dominated by PEG can be stabilized against annealing by dopamine deposition. By the combination use of annealing and dopamine deposition, a series of microspheres with robust surface topologies are facilely prepared. The fuzzy microstructures and dopamine deposition show a synergetic role to enhance cell-material interaction, leading to a larger number of adherent bone marrow-derived mesenchymal stem cells (BMSCs), A549 and MC 3T3 cells. The fuzzy microspheres with dopamine deposition can significantly promote bone regeneration 12 w post surgery in vivo, as revealed by micro-CT, histological, western blotting and RT-PCR analyses.

Dimethyl Itaconate-Loaded Nanofibers Rewrite Macrophage Polarization, Reduce Inflammation, and Enhance Repair of Myocardic Infarction.

Cellular metabolism plays a major role in the regulation of inflammation. The inflammatory macrophages undergo a wide-range of metabolic rewriting due to the production of significant amount of itaconate metabolite from cis-aconitate in the tricarboxylic acid cycle. This itaconate molecule has been recently described as a promising immunoregulator. However, its function and mode of action on macrophages and tissue repair and regeneration are yet unclear. Herein, the itaconate-derivative dimethyl itaconate (DMI) suppresses the IL-23/IL-17 inflammatory axis-associated genes and promotes antioxidant nuclear factor erythroid 2-related factor 2 target genes. The poly-ε-caprolactone (PCL)/DMI nanofibers implanted in mice initially maintain inflammation by suppressing anti-inflammatory activity and particular inflammation, while at later stage promotes anti-inflammatory activity for an appropriate tissue repair. Furthermore, the PCL/DMI nanofiber patches show an excellent myocardial protection by reducing infarct area and improving ventricular function via time-dependent regulation of myocardium-associated genes. This study unveils potential DMI macrophage modulatory functions in tissue microenvironment and macrophages rewriting for proper tissue repair.

Adsorption of serum proteins on titania nanotubes and its role on regulating adhesion and migration of mesenchymal stem cells.

Migration and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) is an important biological process in tissue regeneration. Nanostructured titanium materials are believed to play a fundamental role in dental and orthopedic applications. However, the protein adsorption on nanostructured titanium materials and its correlation with the subsequent cell behaviors have not been studied. In this work, the titania nanotube arrays with different tubular diameters ranging from 27.3 to 88.2 nm were fabricated by using an electrochemical etching method. The adsorbed amounts and types of cell adhesion-related proteins (such as fibronectin, vitronectin, and laminin) from serum were investigated, revealing that these proteins were preferred to bind onto the surface with nanotubes of a smaller diameter. Adhesion and migration of BMSCs were studied as a function of different nanotube diameters in the presence or absence of serum proteins. Compared with the nanotube surface with a larger tubular diameter (88.2 nm), the surface with a smaller one could better support BMSCs in terms of adhesion and spreading. The pre-adsorbed serum proteins significantly enhanced adhesion and migration abilities of BMSCs. However, the adequate interactions between cells and serum proteins on the nanotubes surface with smallest nanotubes in diameter weakened cell mobility. Arrangement of cytoskeleton and expressions of key genes and proteins were studied, revealing that the nanostructured surfaces and pre-adsorbed proteins jointly mediated the adhesion and migration of BMSCs.

Unsaturated polyurethane films grafted with enantiomeric polylysine promotes macrophage polarization to a M2 phenotype through PI3K/Akt1/mTOR axis.

The immune system responds immediately to tissue trauma and to biomaterial implants under the participation of M1/M2 macrophages polarization. The surface properties of biomaterials can significantly influence the tissue repair progress through modulating the macrophage functions. In this study, the surface of poly(propylene fumarate) polyurethane films (PPFU) is grafted with a same density of enantiomeric poly-l-lysine (PPFU-g-PLL) and poly-d-lysine (PPFU-g-PDL), leading to a similar level of enhanced surface wettability for the PPFU-g-PLL and PPFU-g-PDL. The polylysine-grafted PPFU can restrict the M1 polarization, whereas promote M2 polarization of macrophages in vitro, judging from the secretion of cytokines and expression of key M1 and M2 related genes. Comparatively, the PPFU-g-PDL has a stronger effect in inducing M2 polarization in vivo, resulting in a thinner fibrous capsule surrounding the implant biomaterials. The CD44 and integrins of macrophages participate in the polarization process probably by activating focal adhesion kinase (FAK) and Rho-associated protein kinase (ROCK), and downstream PI3K/Akt1/mTOR signal axis to up regulate M2 related gene expression. This study confirms for the first time that polylysine coating is an effective method to regulate the immune response of biomaterials, and the polylysine-modified thermoplastic PPFU with the advantage to promote M2 polarization may be applied widely in regenerative medicine.

Methylcobalamin-Loaded PLCL Conduits Facilitate the Peripheral Nerve Regeneration.

The feasible fabrication of nerve guidance conduits (NGCs) with good biological performance is important for translation in clinics. In this study, poly(d,l-lactide-co-caprolactone) (PLCL) films loaded with various amounts (wt; 5%, 15%, 25%) of methylcobalamin (MeCbl) are prepared, and are further rolled and sutured to obtain MeCbl-loaded NGCs. The MeCbl can be released in a sustainable manner up to 21 days. The proliferation and elongation of Schwann cells, and the proliferation of Neuro2a cells are enhanced on these MeCbl-loaded films. The MeCbl-loaded NGCs are implanted into rats to induce the regeneration of 10 mm amputated sciatic nerve defects, showing the ability to facilitate the recovery of motor and sensory function, and to promote myelination in peripheral nerve regeneration. In particular, the 15% MeCbl-loaded PLCL conduit exhibits the most satisfactory recovery of sciatic nerves in rats with the largest diameter and thickest myelinated fibers.

Surface-Anchored Graphene Oxide Nanosheets on Cell-Scale Micropatterned Poly(d,l-lactide-co-caprolactone) Conduits Promote Peripheral Nerve Regeneration.

Regeneration and functional recovery of peripheral nerves remain formidable due to the inefficient physical and chemical cues in the available nerve guidance conduits (NGCs). Introducing micropatterns and bioactive substances into the inner wall of NGCs can effectively regulate the behavior of Schwann cells, the elongation of axons, and the phenotype of macrophages, thereby aiding the regeneration of injured nerve. In this study, linear micropatterns with ridges and grooves of 3/3, 5/5, 10/10, and 30/30 µm were created on poly(d,l-lactide-co-caprolactone) (PLCL) films following with surface aminolysis and electrostatic adsorption of graphene oxide (GO) nanosheets. The GO-modified micropatterns could significantly accelerate the collective migration of Schwann cells (SCs) and migration of SCs from their spheroids in vitro. Moreover, the SCs migrated directionally along the stripes with a fastest rate on the 3/3-GO film that had the largest cell adhesion force. The neurites of N2a cells were oriented along the micropatterns, and the macrophages tended to differentiate into the M2 type on the 3/3-GO film judged by the higher expression of Arg 1 and IL-10. The systematic histological and functional assessments of the regenerated nerves at 4 and 8 weeks post-surgery in vivo confirmed that the 3/3-GO NGCs had better performance to promote the nerve regeneration, and the CMAP, NCV, wet weight of gastrocnemius muscle, positive S100ß and NF200 area percentages, and average myelinated axon diameter were more close to those of the autograft group at 8 weeks. This type of NGCs thus has a great potential for nerve regeneration.

Temperature-Gating Titania Nanotubes Regulate Migration of Endothelial Cells.

External stimuli-responsive biomaterials represent a type of promising candidates for addressing the complexity of biological systems. In this study, a platform based on the combination of temperature-sensitive polymers and a nanotube array was developed for loading sphingosine 1-phosphate (S1P) and regulating the migration of endothelial cells (ECs) at desired conditions. The localized release dosage of effectors could be controlled by the change of environmental temperature. At a culture temperature above the lower critical solution temperature, the polymer "gatekeeper" with a collapsed conformation allowed the release of S1P, which in turn enhanced the migration of ECs. The migration rate of single cells was significantly enhanced up to 58.5%, and the collective migration distance was also promoted to 25.1% at 24 h and 33.2% at 48 h. The cell morphology, focal adhesion, organization of cytoskeleton, and expression of genes and proteins related to migration were studied to unveil the intrinsic mechanisms. The cell mobility was regulated by the released S1P, which would bind with the S1PR1 receptor on the cell membrane and trigger the Rho GTPase pathway.