Unveiling protein corona composition:predicting with resampling embedding and machine learning

Biomaterials with surface nanostructures effectively enhance protein secretion and stimulate tissue regeneration.When nanoparticles(NPs)enter the living system,they quickly interact with proteins in the body fluid,forming the protein corona(PC).The accurate prediction of the PC composition is critical for analyzing the osteoinductivity of biomaterials and guiding the reverse design of NPs.However,achieving accurate predictions remains a significant challenge.Although several machine learning(ML)models like Random Forest(RF)have been used for PC prediction,they often fail to consider the extreme values in the abundance region of PC absorption and struggle to improve accuracy due to the imbalanced data distribution.In this study,resampling embedding was introduced to resolve the issue of imbalanced distribution in PC data.Various ML models were evaluated,and RF model was finally used for prediction,and good correlation coefficient(R^(2))and root-mean-square deviation(RMSE)values were obtained.Our ablation experiments demonstrated that the proposed method achieved an R^(2) of 0.68,indicating an improvement of approximately 10%,and an RMSE of 0.90,representing a reduction of approximately 10%.Furthermore,through the verification of label-free quantification of four NPs:hydroxyapatite(HA),titanium dioxide(TiO_(2)),silicon dioxide(SiO_(2))and silver(Ag),and we achieved a prediction performance with an R^(2) value>0.70 using Random Oversampling.Additionally,the feature analysis revealed that the composition of the PC is most significantly influenced by the incubation plasma concentration,PDI and surface modification.

Fabrication of microwave-sensitized nanospheres of covalent organic framework with apatinib for tumor therapy

A new nanocomposite of hollow covalent organic framework(COF)conjugated with the apatinib(AP)and loading microwave-sensitizer(ionic liquid,IL)was prepared by layer by layer(LBL)method and hyaluronic acid(HA)coating,named as COF-AP-IL@HA.AP loading rate in COF hollow-spheres(~30 nm shell thickness)was~40.3%,due to the interactions of hydrogen andπ-πbonds between AP and COF shell,and acidic environment destroyed COF structure,promoting AP release.Microwave sensitization of loaded IL in COF hollow-spheres could enhance the microwave heat-effect,and combined AP therapeutic ability,leading to their higher inhibitation on tumor,due to targeting ability of HA and the local release of apatinib.88.9%of inhibition rate of COF-AP-IL@HA under microwave on the in vivo tumor was significantly higher than those without microwave(12.3%)and COF-IL@HA with microwave(37.5%),indicating a synergism of sensitized microwave hyperthermia and AP therapy on the reduced expression of VEGF via the downregulation pathway of hypoxia inducible factor.These results indicated that COF-AP-IL@HA was potential to the application in the combination therapy of tumor of the sensitized microwave hyperthermia and apatinib.

Preparation,properties and biomedical applications progress of 1D magnetic nanomaterials with iron

1D magnetic nanomaterials with iron,with the special physical properties and biological behaviour,have been found to possess the great promising applications in many fields.In this review,the components,structure,physicochemical properties,biocompatibility and in vitro and in vivo biomedical functions of magnetic nanowires(MNWs),nanorods(MNRs)with iron are summarised,especially their anisotropy shape and magnetism result in their many applications in biodetections and medical treatment fields.The potential future functions of these 1D magnetic nanomaterials compared to magnetic nanoparticles also is discussed by highlighting the possibility of integration with other metal-compositions or bio-compositions and with existing biotechnology as well as by point-ing out their specific properties.Current limitations in the property improvement and issues related with the outcome of the MNRs in the body are also summarised in order to address the remaining challenge for the extended biomedical functions of MNRs in the clinical application field.

A novel akermanite/poly (lactic-co-glycolic acid) porous composite scaffold fabricated via a solvent casting-particulate leaching method improved by solvent self-proliferating process

Desirable scaffolds for tissue engineering should be biodegradable carriers to supply suitablemicroenvironments mimicked the extracellular matrices for desired cellular interactions and to providesupports for the formation of new tissues. In this work, a kind of slightly soluble bioactiveceramic akermanite (AKT) powders were aboratively selected and introduced in the PLGA matrix,a novel L-lactide modified AKT/poly (lactic-co-glycolic acid) (m-AKT/PLGA) composite scaffold wasfabricated via a solvent casting-particulate leaching method improved by solvent self-proliferatingprocess. The effects of m-AKT contents on properties of composite scaffolds and on MC3T3-E1 cellularbehaviors in vitro have been primarily investigated. The fabricated scaffolds exhibited threedimensionalporous networks, in which homogenously distributed cavities in size of 300–400 lmwere interconnected by some smaller holes in a size of 100–200 lm. Meanwhile, the mechanicalstructure of scaffolds was reinforced by the introduction of m-AKT. Moreover, alkaline ionic productsreleased by m-AKT could neutralize the acidic degradation products of PLGA, and the apatitemineralizationability of scaffolds could be largely improved. More valuably, significant promotionson adhesion, proliferation, and differentiation of MC3T3-E1 have been observed, which implied thecalcium, magnesium and especially silidous ions released sustainably from composite scaffoldscould regulate the behaviors of osteogenesis-related cells.

Fabrication of extracellular matrix-coated conductive polypyrrolepoly(L-lactide)fiber-films and their synergistic effect with(nerve growth factor)/(epidermal growth factor) on neurites growth

Non-nerve cell-derived extracellular matrix(ECM)wa s coated on the aligned porous polypyrrole-poly(Llactide)(PPy-PLLA)fiber-films with the conductivity of^12 mS/m via L929 cells culture and lysing,resulting in^10%increase of PC12 cells attachment and^26μm increase of neurites length.The neurite length of^149μm in EGF/NGF group(optimal concentration radio of 12.5/50(ng/mL))on aligned and ECM-conjugated fiber-films was significantly larger than^94μm in only NGF group(50 ng/mL),confirming the synergy of EGF,NGF and aligned ECM-conjuaged PPy-PLLA fibers.When differentiated PC12 cells were exerted electrical stimulation(ES)of 100 mV/cm for 4 h/day in 2 day through ECM-PPyPLLA fiber-films,their neurite length reached to^251μm,significantly larger than^149μm of group without ES,due to the higer expression of related neural proteins in ES group.A simple mechanism was proposed to analyze synergistical effect of ECM,EGF,NGF on axons adhesion and elongation along the aligned ECM-coated fibers under ES condition.

MBG/PGA-PCL composite scaffolds provide highly tunable degradation and osteogenic features

It remains a challenge to achieve satisfactory balance between biodegradability and osteogenic capacity in biosynthetic bone grafts.In this study,we aimed to address this challenge by incorporating mesoporous bioactive glass(MBG)into poly(caprolactone-co-glycolide)(PGA-PCL)at gradient ratios.MBG/PGA-PCL(PGC/M)scaffolds with MBG incorporation ratio at 0,10%,25%and 40%(PGC/M0-40)were synthesized using a modified solvent casting-particulate leaching method,and their physiochemical and biological properties were comprehensively evaluated.PGC/M scaffolds exhibited highly perforated porous structure with a large-pore size of 300-450μm,with ordered MBGs of around 6.0 nm mesopores size uniformly dispersed.The increase in MBG incorporation ratio significantly improved the scaffold surface hydrophilicity,apatite-formation ability and pH stability,increased the weight loss rate while insignificantly influenced the molecular chains degradation of PGA-PCL component,and facilitated the attachment,spreading,viability and proliferation of rat bone marrow stromal cells(rBMSCs)on scaffolds.Moreover,rBMSCs cultured on PGC/M10-40 scaffolds demonstrated enhanced ALP activity and osteogenesis-related gene expression in a MBG dose-dependent manner as compared with those cultured on PGC/M0 scaffolds.When implanted to the rat cranial bone defect,PGC/M25 and PGC/M40 scaffolds induced significantly better bone repair as compared to PGC/M0 and PGC/M10 scaffolds.Besides,the biodegradability of PGC/M scaffolds correlated with the MBG incorporation ratio.These data suggested this novel PGC/M scaffolds as promising bone repair biomaterial with highly tunable hydrophilicity,bioactivity,cytocompatibility,osteogenic activity as well as biodegradability.

Fabrication of carboxylic graphene oxide-composited polypyrrole film for neurite growth under electrical stimulation

An aligned composite film was fabricated via the deposition of carboxylic graphe ne oxide(C-GO)and polypyrrole(PPy)nano particles on alig ned poly(L-lactic acid)(PLLA)fiber-films(named as C-GO/PPy/PLLA),which has the core(PLLA)-sheath(C-GO/PPy)structure,and the composition of C-GO(~4.8 wt.%of PPy sheath)significantly enhanced the tensile strength and the conductivity of the PPy/PLLA film?Especially,after 4 weeks of immersion in the PBS solution,the conductivity and the tensile strength of CGO/PPy/PLLA films still remained-6.10 S/cm and 28.9 MPa,respectively,which could meet the need of the sustained electrical stimulation(ES)therapy for nerve repair.Moreover,the neurite length and the neurite alignment were significantly in creased through exerting ES on C-GO/PPy/PLLA films due to their sustained conductivity in the fluid of cell culture.These results indicated that C-GO/PPy/PLLA with sustained conductivity and mechanical property possessed great potential of nerve repair by exerting lasting-ES.

Fabrication of doxorubicin and chlorotoxin-linked Eu-Gd2O3 nanorods with dual-model imaging and targeted therapy of brain tumor

It is urgent to find a technology accurately to better diagnose and treat to brain tumor.Eu-doped Gd2 O3 nanorods(Eu-Gd2 O3 NRs)with paramagnetic and fluorescent properties were conjugated with doxorubicin(Dox)and chlorotoxin(CTX)via PEGylation,hydrazone bond and sulfur bond(named as CTXNRs-Dox),and these NRs could release more Dox in lower pH environment.The results of cell experiments indicated that CTX-NRs-Dox had obvious targeting and toxic effects on U251 cells,as well as good fluorescence imaging behavior.The orthotopic glioma-transplanted mice models were constructed via the intracranial injection of glioma cells(U87 MG).The result of experiments after the tail-vein injection of the prepared NRs suggested that CTX-NRs-Dox could target to brain tumors via the long-time blood circulation,leading to their obvious contrast enhancement of MR imaging of the intracranial tumor and their significant inhibitory effect on the growth and metastasis of brain tumors.A mechanism of synergistic effect of CTX-NRs-Dox on targeting and inhabiting the brain tumor was proposed.Our research suggested that CTX-NRs-Dox had potential application prospect in the detection and treatment of glioma.

Biocompatibility of Surface-Modified Biphasic Calcium Phosphate/Poly-L-Lactide Biocomposite in vitro and in vivo

The biocompatibility of surface-modified biphasic calcium phosphate （mBCP）/poly-L-Lactide （PLLA） biocomposite was investigated through a series of experiments in vitro and in vivo. Acute toxicity and short term systemic toxicity experiments revealed no toxicity of the materials. Hemolysis assay indicated the good blood compatibility of the composite. In cytotoxicity assay, L929 mouse fibroblasts could well differentiate and proliferate. Animal experiments in vivo were.performed by implanting the materials into rabbits muscle for 8 weeks. The decreasing of inflammatory cells, the building of fibrous tissue layer as well as the growing of blood cells into materials indicated the nontoxicity of the composite. Based on the experiment results, surfacemodified BCP/PLLA biocomposite is proven to have superior biocompatibility, which would be a promising bone repairing material.