Evaluation of short-term effects of drug-loaded microspheres and traditional transcatheter arterial chemoembolization in the treatment of advanced liver cancer

BACKGROUND Liver cancer is a malignant tumor with high morbidity and mortality.Transcatheter arterial chemoembolization(TACE)is the main method for surgically unresectable liver cancer.In recent years,drug-loaded microspheres have been gradually applied in TACE technology.There are some controversies about the therapeutic effects of drug-loaded microspheres TACE(D-TACE)and traditional TACE.AIM To explore the short-term efficacy of D-TACE and traditional TACE in the treatment of advanced liver cancer.METHODS The clinical data of 73 patients with advanced liver cancer admitted to the First and Sixth Medical Centers of Chinese PLA General Hospital from January 2017 to October 2019 were retrospectively analyzed.Among them,15 patients were treated with D-TACE,and 58 patients were treated with traditional TACE.Clinical baseline characteristics,perioperative laboratory indices,postoperative adverse reactions and postoperative complications were compared between the two groups.RESULTS There was no statistical difference between the two groups for the postoperative response:The highest postoperative body temperature of the drug-loaded microsphere group was 38.0±0.9℃and the postoperative highest body temperature of the traditional TACE group was 38.3±0.7℃(t=-1.414,P=0.162).For the 24 h postoperative nausea and vomiting after surgery in terms of scoring and postoperative pain scores,the traditional TACE group was higher than the drugloaded microsphere group(χ2=14.33,P=0.014;χ2=32.967,P=0.000)and the two groups had significant statistical differences.The disease control rate at 3 mo after treatment in the drugloaded microsphere group was 60%and the disease control rate at 3 mo after treatment in the traditional TACE group was 75.9%(χ2=4.091,P=0.252).There was no statistical difference between the two groups of data.During the follow-up period,the number of interventional treatments received was once in the drug-loaded microsphere group and the traditional TACE group received an average of 1.48 treatments(χ2=10.444 P=0.005).There was a statistical difference between the two groups.CONCLUSION Compared with traditional TACE,D-TACE may have some advantages in the treatment of advanced hepatocellular carcinoma with a large tumor load in the short term,but the long-term clinical efficacy needs additional follow-up studies.In addition,compared with the traditional group,the patients in the drug-loaded microsphere group had better subjective tolerance and could reduce the number of interventional treatments.Therefore,D-TACE is worthy of clinical promotion.

Preparation and Properties of Gelatin-Chitosan/Montmorillonite Drug-loaded Microspheres

A kind of slow release drug-loaded microspheres were prepared with gelatin, chitosan and montmorillonite（MMT） by an emulsification/chemical cross-linking method using glutaraldehyde as cross-linking agent and acyclovir as model drug. The microspheres were characterized by X-ray diffraction （XRD）, Fourier transform infrared （FT-IR） and scanning electron microscopy （SEM）, respectively. The morphology, drug content, encapsulation efficiency and drug-release behavior were investigated with different MMT contents. The experimental results indicated that intercalated microspheres could be prepared, the morphology of microspheres was markedly affected by MMT. The glomeration performance of uncross-linked microspheres was improved because of the physical cross-linking of MMT. Drug content and encapsulation efficiency were decreased when increased the content of MMT, but burst release and the drug release were significantly decreased with the addition of MMT. Effective physical cross-linking could be formed when added MMT, and MMT could reduce the content of toxic chemical cross-linking agents.

Superhydrophobic Surface-Assisted Preparation of Microspheres and Supraparticles and Their Applications

Superhydrophobic surface(SHS) has been well developed, as SHS renders the property of minimizing the water/solid contact interface. Water droplets deposited onto SHS with contact angles exceeding 150°, allow them to retain spherical shapes, and the low adhesion of SHS facilitates easy droplet collection when tilting the substrate. These characteristics make SHS suitable for a wide range of applications. One particularly promising application is the fabrication of microsphere and supraparticle materials. SHS offers a distinct advantage as a universal platform capable of providing customized services for a variety of microspheres and supraparticles. In this review, an overview of the strategies for fabricating microspheres and supraparticles with the aid of SHS, including cross-linking process, polymer melting,and droplet template evaporation methods, is first presented. Then, the applications of microspheres and supraparticles formed onto SHS are discussed in detail, for example, fabricating photonic devices with controllable structures and tunable structural colors, acting as catalysts with emerging or synergetic properties, being integrated into the biomedical field to construct the devices with different medicinal purposes, being utilized for inducing protein crystallization and detecting trace amounts of analytes. Finally,the perspective on future developments involved with this research field is given, along with some obstacles and opportunities.

Optical Microsphere Nano-Imaging:Progress and Challenges

The optical diffraction effect imposes a radical obstacle preventing conventional optical microscopes from achieving an imaging resolution beyond the Abbe diffraction limit and thereby restricting their usage in a multitude of nanoscale applications.Over the past decade,the optical microsphere nanoimaging technique has been demonstrated to be a cost-effective solution for overcoming the diffraction limit and has achieved an imaging resolution of up to about k6k8 in a real-time and label-free manner,making it highly competitive among numerous super-resolution imaging technologies.In this review,we summarize the underlying nano-imaging mechanisms of the microsphere nanoscope and key advancements aimed at imaging performance enhancement:first,to change the working environment or modify the peripheral hardware of a single microsphere nanoscope at the system level;second,to compose the microsphere compound lens;and third,to engineer the geometry or ingredients of microspheres.We also analyze challenges yet to be overcome in optical microsphere nano-imaging,followed by an outlook of this technique.

One-pot Synthesis of Hierarchical Flower-like WS_(2) Microspheres as Anode Materials for Lithium-ion Batteries

3D hierarchical flowerlike WS_(2) microspheres were synthesized through a facile one-pot hydrothermal route.The as-synthesized samples were characterized by powder X-ray powder diffraction (XRD),energy-dispersive spectroscopy (EDS),scanning electron microscopy (SEM) and Raman.SEM images of the samples reveal that the hierarchical flowerlike WS_(2) microspheres with diameters of about 3-5μm are composed of a number of curled nanosheets.Electrochemical tests such as charge/discharge,cyclic voltammetry,cycle life and rate performance were carried out on the WS_(2) sample.As an anode material for lithium-ion batteries,hierarchical flowerlike WS_(2) microspheres show excellent electrochemical performance.At a current density of100 mA·g^(-1),a high specific capacity of 647.8 mA·h·g^(-1) was achieved after 120 discharge/charge cycles.The excellent electrochemical performance of WS_(2) as an anode material for lithium-ion batteries can be attributed to its special 3D hierarchical structure.

Eco-friendly calcium alginate microspheres enable enhanced profile control and oil displacement

Polymer microspheres(PMs),such as polyacrylamide,have been widely applied for enhanced oil recovery(EOR),yet with environmental concerns.Here,we report a microfluid displacement technology containing a bio-based eco-friendly material,i.e.,calcium alginate(CaAlg)microspheres for EOR.Two dominant mechanisms responsible for EOR over Ca Alg fluid have been verified,including the microscopic oil displacement efficacy augmented by regulating capillary force(determined by the joint action of interfacial tension and wettability between different phases)and macroscopic sweep volume increment through profile control and mobility ratio reduction.This comprehensive effectiveness can be further impacted when the CaAlg microsphere is embellished ulteriorly by using appropriate amount of sodium dodecyl sulfonate(SDS).The core flooding and nuclear magnetic resonance(NMR)tests demonstrate that CaAlg-SDS microsphere can balance the interphase property regulation(wettability alteration and IFT reduction)and rheology properties,enabling simultaneous profile control and oil displacement.Excessive introduction of SDS will have a negative impact on rheological properties,which is not favored for EOR.Our results show that the involvement of 4-m M SDS will provide the best behavior,with an EOR rate of 34.38%.This cost-effective and environmentally-friendly bio-microspherebased microfluidic displacement technology is expected to achieve“green”oil recovery in future oilfield exploitation.

MOFs‑Derived Strategy and Ternary Alloys Regulation in Flower‑Like Magnetic‑Carbon Microspheres with Broadband Electromagnetic Wave Absorption

Broadband electromagnetic(EM)wave absorption materials play an important role in military stealth and health protection.Herein,metal–organic frameworks(MOFs)-derived magnetic-carbon CoNiM@C(M=Cu,Zn,Fe,Mn)microspheres are fabricated,which exhibit flower-like nano–microstructure with tunable EM response capacity.Based on the MOFs-derived CoNi@C microsphere,the adjacent third element is introduced into magnetic CoNi alloy to enhance EM wave absorption performance.In term of broadband absorption,the order of efficient absorption bandwidth(EAB)value is Mn>Fe=Zn>Cu in the CoNiM@C microspheres.Therefore,MOFs-derived flower-like CoNiMn@C microspheres hold outstanding broadband absorption and the EAB can reach up to 5.8 GHz(covering 12.2–18 GHz at 2.0 mm thickness).Besides,off-axis electron holography and computational simulations are applied to elucidate the inherent dielectric dissipation and magnetic loss.Rich heterointerfaces in CoNiMn@C promote the aggregation of the negative/positive charges at the contacting region,forming interfacial polarization.The graphitized carbon layer catalyzed by the magnetic CoNiMn core offered the electron mobility path,boosting the conductive loss.Equally importantly,magnetic coupling is observed in the CoNiMn@C to strengthen the magnetic responding behaviors.This study provides a new guide to build broadband EM absorption by regulating the ternary magnetic alloy.

Construct a 3D microsphere of HMX/B/Al/PTFE to obtain the high energy and combustion reactivity

Metal(aluminum and boron)based energetic materials have been wildly applied in various fields including aerospace,explosives and micro-devices due to their high energy density.Unfortunately,the low combustion efficiency and reactivity of metal fuels,especially boron(B),severely limit their practical applications.Herein,multi-component 3D microspheres of HMX/B/Al/PTFE(HBA)have been designed and successfully prepared by emulsion and solvent evaporation method to achieve superior energy and combustion reactivity.The reactivity and energy output of HBA are systematically measured by ignitionburning test,constant-volume explosion vessel system and bomb calorimetry.Due to the increased interfacial contact and reaction area,HBA shows higher flame propagation rate,faster pressurization rate and larger combustion heat of 29.95 cm/s,1077 kPa/s,and 6164.43 J/g,which is 1.5 times,3.5 times,and 1.03 times of the physical mixed counterpart(HBA-P).Meanwhile,HBA also shows enhanced energy output and reactivity than 3D microspheres of HMX/B/PTFE(HB)resulting from the high reactivity of Al.The reaction mechanism of 3D microspheres is comprehensively investigated through combustion emission spectral and thermal analysis(TG-DSC-MS).The superior reactivity and energy of HBA originate from the surface etching of fluorine to the inert shell(Al_(2)O_(3) and B_(2)O_(3))and the initiation effect of Al to B.This work offers a promising approach to design and prepare high-performance energetic materials for the practical applications.

Optimization of Preparation of Oregano Oil Microspheres by Box-Behnken Response Surface Methodology

[Objectives]To optimize the formulation and preparation of oregano oil microspheres by Box-Behnken response surface methodology.[Methods]Chitosan was used as the carrier material to prepare oregano oil microspheres by emulsion crosslinking method.The encapsulation efficiency,drug loading and ID 50 were used as the evaluation indicators,and the comprehensive score(OD)obtained by"coefficient of variation-AHP comprehensive weighting method"was used as the final evaluation indicator.The formulation design and preparation process were optimized by single factor experiment and Box-Behnken response surface methodology,and the optimal process parameters were determined.[Results]The optimal formulation and preparation process parameters of oregano oil microspheres were as follows:the ratio of oregano oil to chitosan was 2∶1,the emulsifying speed of double emulsion was 200 r/min,the amount of emulsifier in the colostrum was 4%,and the volume of curing agent was 1.0 mL.The average encapsulation efficiency was 45.33%±1.32%,the average drug loading was 30.59%±2.45%,and the median diameter(ID 50)was 52.596μm±0.023%.[Conclusions]The encapsulation efficiency,drug loading and ID 50 of oregano oil chitosan microspheres prepared by emulsion crosslinking method met the requirements.The drug-loaded microsphere not only can be used as a preparation finished product for direct application,but also be used as a product intermediate to lay a foundation for the research and development of subsequent dosage forms.

Tissue Regeneration in Infected Wounds of Albino Rats Using Ciprofloxacin-Loaded Gelatin Microspheres Incorporated Collagen Scaffold: A Histological Approach with H&E Staining

A wound care system consisting of ciprofloxacin-loaded gelatin microspheres impregnated in a macroporous collagen scaffold was created to effectively control wound infection and regenerate soft tissue at the wound site.Histological and biochemical alterations were observed in infected wounds treated with these scaffolds in Albino Wistar rats.Furthermore,the study examined the immediate and prolonged release of ciprofloxacin from the scaffolds,as well as their function in eliminating bacterial infections and expediting the process of skin healing and regeneration.The developed technique was followed in the streamlined process of creating these collagen scaffolds.Compared to untreated wounds,the group receiving scaffold treatment experienced a faster rate of wound closure.It was noted that the rate of infections was considerably reduced and that full soft tissue regeneration occurred within 12 days.The development of well-deposited collagen bundles in the treated groups was demonstrated by H&E staining,which verified the flawless regeneration of the dermis and epidermis.The antimicrobial agent-loaded gelatin microspheres impregnated into the porous collagen scaffold demonstrated remarkable soft tissue regeneration and efficient infection control at the wound site.

Research Progress on the Preparation of Inorganic/Natural Materials Composite Microspheres

Microspheres are a new type of drug carrier with great potential for development and application.Natural polymers have good biocompatibility,biodegradability,and are easily dispersed in living organisms,making them suitable for preparing microspheres.Inorganic materials(mainly inorganic minerals)have excellent mechanical properties and are inexpensive and easy to obtain.Through the coupling and hybridization of natural polymers and inorganic materials,they can complement each other's advantages and synergistically enhance efficiency,resulting in many excellent physical and chemical properties.Inorganic materials/natural polymer composite microspheres can be prepared by modifying natural polymers with inorganic materials through various methods such as emulsification crosslinking,solution mixing,in-situ synthesis,extrusion,etc.The application of inorganic materials/natural polymer composite microspheres in drug delivery systems has significant sustained-release effects,is safe and non-toxic,and the cost of carrier materials is relatively low,which has certain significance for the development of new drug carriers.This article reviews the recent research on the preparation,drug loading and release properties of inorganic material/natural polymer composite microspheres,analyzes the advantages and disadvantages of commonly used preparation methods,and looks forward to the development direction of composite microspheres.

Preparation and in vitro Release Properties of Mercaptopurine Drug-loaded Magnetic Microspheres

Magnetic Fe304 nanoparticles were synthesized by co-precipitation method and the mercaptopurine （MER） drug-loaded magnetic microspheres were obtained through emulsion cross-linking methods. The efficiency of this approach was evaluated in terms of drug loading content （DLC）, encapsulation efficiency （EE） and delivery properties in vitro, determined by high performance liquid chromatograph （HPLC）. The microspheres showed good DLC values of 11.8%, as well as good EE values of 79.4%. The in vitro drug release study was carried out in phosphate buffer solution （PBS） simulated body fluid, at 37 ~C with pH=7.4. The release profiles showed an initial fast release rate, which decreased as time progressed and about 84 % had been released after 48 h. The experimental results indicated that the prepared magnetic microspheres may be useful for potential applications of MER for magnetically targeted chemotherapy.

Boosting Interfacial Polarization Through Heterointerface Engineering in MXene/Graphene Intercalated-Based Microspheres for Electromagnetic Wave Absorption

Multi-layer 2D material assemblies provide a great number of interfaces beneficial for electromagnetic wave absorption.However,avoiding agglomeration and achieving layer-by-layer ordered intercalation remain chal-lenging.Here,3D reduced graphene oxide(rGO)/MXene/TiO_(2)/Fe_(2)C lightweight porous microspheres with periodical intercalated structures and pronounced inter-facial effects were constructed by spray-freeze-drying and microwave irradiation based on the Maxwell–Wagner effect.Such approach reinforced interfacial effects via defects introduction,porous skeleton,multi-layer assembly and multi-compo-nent system,leading to synergistic loss mechanisms.The abundant 2D/2D/0D/0D intercalated heterojunctions in the microspheres provide a high density of polari-zation charges while generating abundant polarization sites,resulting in boosted interfacial polarization,which is verified by CST Microwave Studio simulations.By precisely tuning the 2D nanosheets intercalation in the heterostructures,both the polarization loss and impedance matching improve significantly.At a low filler loading of 5 wt%,the polarization loss rate exceeds 70%,and a minimum reflection loss(RLmin)of-67.4 dB can be achieved.Moreover,radar cross-section simulations further confirm the attenuation ability of the optimized porous microspheres.These results not only provide novel insights into understanding and enhancing interfacial effects,but also constitute an attractive platform for implementing heterointerface engineering based on customized 2D hierarchical architectures.

Microsphere femtosecond laser sub-50 nm structuring in far field via non-linear absorption

Creation of arbitrary features with high resolution is critically important in the fabrication of nano-optoelectronic devices.Here,sub-50 nm surface structuring is achieved directly on Sb2S3 thin films via microsphere femtosecond laser irradi-ation in far field.By varying laser fluence and scanning speed,nano-feature sizes can be flexibly tuned.Such small patterns are attributed to the co-effect of microsphere focusing,two-photons absorption,top threshold effect,and high-repetition-rate femtosecond laser-induced incubation effect.The minimum feature size can be reduced down to~30 nm(λ/26)by manipulating film thickness.The fitting analysis between the ablation width and depth predicts that the feature size can be down to~15 nm at the film thickness of~10 nm.A nano-grating is fabricated,which demonstrates desirable beam diffraction performance.This nano-scale resolution would be highly attractive for next-generation laser nano-lithography in far field and in ambient air.

Exploration of the Exceptional Capacitive Deionization Performance of CoMn_(2)O_(4) Microspheres Electrode

The“battery type”inorganic electrode has been demonstrated the highly efficient sodium ion intercalation capacity for capacitive deionization.In this work,the CoMn_(2)O_(4)(CMO)microspheres with porous core-shell structure are prepared via co-precipitation and followed by annealing.The effects of annealing temperatures on the morphology,pore structure,valence state,and electrochemical behavior of CMO are explored.As electrode for capacitive deionization,the salt removal capacity and current efficiency of optimized AC||CMO device reaches up to 60.7 mg g^(−1) and 97.6%,respectively,and the capacity retention rate is 74.1%after 50 cycles.Remarkably,both the in-situ X-ray diffraction and ex-situ X-ray diffraction analysis features that the intercalation/de-intercalation of sodium ions are governed by(103)and(221)crystal planes of CMO.Accordingly,the density functional theory calculations realize that the adsorption energies of Na+onto(103)and(221)crystal planes are higher than that of any other crystal planes,manifesting the priorities in adsorption of sodium atoms.Furthermore,the X-ray photoelectron spectra of pristine and post-CMO electrode highlights that the reversible conversion of Mn^(3+)/Mn^(4+)couple is resulted from the intercalation/de-intercalation of Na^(+),while this is irreversible for Co^(3+)/Co^(2+)couple.Beyond that,the CMO electrode has been proven the selectivity removal of Na^(+) over K^(+)and Mg^(2+)in a multi-cation stream.

Waste to wealth: Oxygen-nitrogen-sulfur codoped lignin-derived carbon microspheres from hazardous black liquors for high-performance DSSCs

Carbon materials are effective substitutes for Pt counter electrodes(CEs) in dye-sensitized solar cells(DSSCs). However, many of these materials, such as carbon nanotubes and graphene, are expensive and require complex preparation process. Herein, waste lignin, recycled from hazardous black liquors,is used to create oxygen-nitrogen-sulfur codoped carbon microspheres for use in DSSC CEs through the facile process of low-temperature preoxidation and high-temperature self-activation. The large number of ester bonds formed by preoxidation increase the degree of cross-linking of the lignin chains, leading to the formation of highly disordered carbon with ample defect sites during pyrolysis. The presence of organic O/N/S components in the waste lignin results in high O/N/S doping of the pyrolysed carbon,which increases the electrolyte ion adsorption and accelerates the electron transfer at the CE/electrolyte interface, as confirmed by density functional theory(DFT) calculations. The presence of inorganic impurities enables the construction of a hierarchical micropore-rich carbon structure through the etching effect during self-activation, which can provide abundant catalytically active sites for the reversible adsorption/desorption of electrolyte ions. Under these synergistic effects, the DSSCs that use this novel carbon CE achieve a quite high power-conversion efficiency of 9.22%. To the best of our knowledge, the value is a new record reported so far for biomass-carbon-based DSSCs.

Poly(lactic acid)-aspirin microspheres prepared via the traditional and improved solvent evaporation methods and its application performances

Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.

Thermal and ignition properties of hexanitrostilbene(HNS) microspheres prepared by droplet microfluidics

HNS-IV(Hexanitrostilbene-IV) is the main charge of the exploding foil initiators(EFI), and the microstructure of the HNS will directly affect its density, flowability, sensitivity, and stability. HNS microspheres were prepared using droplet microfluidics, and the particle size, morphology, specific surface area, thermal performance, and ignition threshold of the HNS microspheres were characterized and tested. The results shown that the prepared HNS microspheres have high sphericity, with an average particle size of 20.52 μm(coefficient of variation less than 0.2), and a specific surface area of 21.62 m^(2)/g(6.87 m^(2)/g higher than the raw material). Without changing the crystal structure and thermal stability of HNS-IV, this method significantly enhances the sensitivity of HNS-IV to short pulses and reduces the ignition threshold of the slapper detonator to below 1000 V. This will contribute to the miniaturization and low cost of EFI.

High drug loading hydrophobic cross-linked dextran microspheres as novel drug delivery systems for the treatment of osteoarthritis

Drug delivery via intra-articular(IA)injection has proved to be effective in osteoarthritis(OA)therapy,limited by the drug efficiency and short retention time of the drug delivery systems(DDSs).Herein,a series of modified cross-linked dextran(Sephadex,S0)was fabricated by respectively grafting with linear alkyl chains,branched alkyl chains or aromatic chain,and acted as DDSs after ibuprofen(Ibu)loading for OA therapy.This DDSs expressed sustained drug release,excellent anti-inflammatory and chondroprotective effects both in IL-1βinduced chondrocytes and OA joints.Specifically,the introduction of a longer hydrophobic chain,particularly an aromatic chain,distinctly improved the hydrophobicity of S0,increased Ibu loading efficiency,and further led to significantly improving OA therapeutic effects.Therefore,hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.

Nerve growth factor-basic fibroblast growth factor poly-lactide co-glycolid sustained-release microspheres and the small gap sleeve bridging technique to repair peripheral nerve injury

We previously prepared nerve growth factor poly-lactide co-glycolid sustained-release microspheres to treat rat sciatic nerve injury using the small gap sleeve technique.Multiple growth factors play a synergistic role in promoting the repair of peripheral nerve injury;as a result,in this study,we added basic fibroblast growth factors to the microspheres to further promote nerve regeneration.First,in an in vitro biomimetic microenvironment,we developed and used a drug screening biomimetic microfluidic chip to screen the optimal combination of nerve growth factor/basic fibroblast growth factor to promote the regeneration of Schwann cells.We found that 22.56 ng/mL nerve growth factor combined with 4.29 ng/mL basic fibroblast growth factor exhibited optimal effects on the proliferation of primary rat Schwann cells.The successfully prepared nerve growth factor-basic fibroblast growth factor-poly-lactide-co-glycolid sustained-release microspheres were used to treat rat sciatic nerve transection injury using the small gap sleeve bridge technique.Compared with epithelium sutures and small gap sleeve bridging alone,the small gap sleeve bridging technique combined with drug-free sustained-release microspheres has a stronger effect on rat sciatic nerve transfection injury repair at the structural and functional level.