Yumeng Xue

A highly bioactive and biodegradable poly(glycerol sebacate)–silica glass hybrid elastomer with tailored mechanical properties for bone tissue regeneration

Biodegradable poly(glycerol sebacate) (PGS) elastomers have received much attention as promising materials for potential applications in soft tissue repair and regeneration, due to their biomimetic viscoelastic properties. However, the low strength and the absence of bioactivity have limited their potential applications in hard (bone, tooth, tendon and ligament) tissue regeneration. Here, we introduced the molecular-level silica bioactive glass into the matrix of polymer elastomers to prepare bioactive hybrid elastomers (PGSSC) for bone tissue regeneration applications. We have shown here that our PGSSC provide some advantages over conventional bioactive materials and elastomers due to their controlled biomineralization (apatite-forming bioactivity), tunable elastic properties and biodegradation, and enhanced osteoblast proliferation. The tensile strength and the initial modulus of PGSSC hybrid elastomers ranged from 1 to 5 MPa and 2 to 32 MPa respectively by controlling silica phase contents, which are several times higher than pure PGS elastomers. PGSSC elastomers also showed enhanced hydrophilicity with contact angle ranging from 75 to 25 degree. The biological apatite was formed on the surfaces of PGSSC when soaked in simulated body fluid (SBF) for 1 day. The osteoblast (MC3T3) demonstrated significantly enhanced proliferation on PGSSC compared with PGS. The development of bioactive PGSSC hybrid elastomers may offer a new choice for bone tissue repair and regeneration.

Monodisperse photoluminescent and highly biocompatible bioactive glass nanoparticles for controlled drug delivery and cell imaging

Bioactive glass nanoparticles (BGNs) have attracted widespread interest recently and been explored as the promising drug or gene delivery carriers due to their high biocompatibility and tissue repair ability. However, the synthesis of monodispersed photoluminescent BGNs and their corresponding biomedical applications are still not explored. Here, for the first time, we report monodispersed Eu-doped photoluminescent bioactive glass nanoparticles (BGN-Eu) and demonstrate their biomedical applications for drug delivery and cell imaging. By a long chain amine assisted sol-gel method, we synthesized the monodispersed BGN-Eu with combined dual functions of bioactivity and luminescence properties, and further investigated their physicochemical structure, biomineralization activity and biomedical applications. As-prepared BGN-Eu possessed the spherical morphology, relatively homogeneous particle size (200 ∼ 400 nm) and representative red fluorescence emission characteristic of Eu3+ at 616 nm. In simulated body fluids (SBFs), the BGN-Eu demonstrated excellent bioactivity by inducing biological apatite mineralization. BGN-Eu also presented controlled drug (theophylline) loading ability and release behavior. The osteoblast (MC3T3) growth was significantly enhanced when incubated with different dosages of BGN-Eu, suggesting the high biocompatibility. In addition, BGN-Eu was successfully used to label the MC3T3 cell by a strong red fluorescence with low background noise. Our results suggest the great potential of BGN-Eu as multifunctional bioactive nanomaterials for cell imaging and bone tissue regeneration applications.

High quality β-FeOOH nanostructures constructed by a biomolecule-assisted hydrothermal approach and their pH-responsive drug delivery behaviors

β-FeOOH nanostructures with diverse well-defined morphologies such as urchin-like, bowknot-like and bamboo leaf-like structures have been obtained by controlled synthesis by a facile gelatin-assisted hydrothermal approach. The as-obtained β-FeOOH nanostructures presented promising pH-controlled anti-cancer drug delivery behaviors and low cytotoxicity and high cellular biocompatibility features.

Intrinsic Ultrahigh Drug/miRNA Loading Capacity of Biodegradable Bioactive Glass Nanoparticles toward Highly Efficient Pharmaceutical Delivery.

The lack of safe and efficient drug and gene delivery vectors has become a major obstacle for the clinical applications of drug and nonviral gene therapy. To date, for nonviral gene vectors, most studies are focused on cationic polymers, liposomes, and modified inorganic nanoparticles which have shown high cellular toxicity, low transfection efficiency, or nondegradation. Additionally, few biodegradable biomaterials demonstrate intrinsic high binding abilities to both drug and gene. Bioactive glasses (BGs) have achieved successful applications in bone regeneration due to their high biocompatibility and biodegradation. Here, for the first time, we demonstrate the intrinsic ultrahigh drug and miRNA binding ability of bioactive glass nanoparticles (BGNs) without any cationic polymer modification. BGNs demonstrate an over 45-fold improvement in hydrophilic drug loading (diclofenac sodium) and 7-fold enhancement in miRNA binding over their corresponding silica nanoparticles. The hydrophilic drug loading ability of BGNs (>45 wt % loading) is also higher than that of most other reported inorganic nanoparticles, including mesoporous silica nanoparticles. BGNs show significantly lower cytotoxicity and higher cellular uptake and miRNA transfection efficiency compared to those of commercial transfection reagents polyethylenimine and lipofectamine 3000. Our results demonstrate that BGNs may become a new competitive vehicle for drug and gene delivery applications. This study may also provide a new strategy to develop novel biomaterials with intrinsic drug and gene binding ability for disease therapy.

Biodegradable, Elastomeric, and Intrinsically Photoluminescent Poly(Silicon-Citrates) with high Photostability and Biocompatibility for Tissue Regeneration and Bioimaging

Biodegradable polymer biomaterials with intrinsical photoluminescent properties have attracted much interest, due to their potential advantages for tissue regeneration and noninvasive bioimaging. However, few of current biodegradable polymers possess tunable intrinsically fluorescent properties, such as high photostability, fluorescent lifetime, and quantum field, and strong mechanical properties for meeting the requirements of biomedical applications. Here, by a facile one-step thermal polymerization, elastomeric poly(silicone-citrate) (PSC) hybrid polymers are developed with controlled biodegradability and mechanical properties, tunable inherent fluorescent emission (up to 600 nm), high photostability (beyond 180 min for UV and six months for natural light), fluorescent lifetime (near 10 ns) and quantum yield (16%-35%), high cellular biocompatibility, and minimal inflammatory response in vivo, which provide advantages over conventional fluorescent dyes, quantum dots, and current fluorescent polymers. The promising applications of PSC hybrids for cell and implants imaging in vitro and in vivo are successfully demonstrated. The development of elastomeric PSC polymer may provide a new strategy in synthesizing new inorganic-organic hybrid photo-luminescent materials for tissue regeneration and bioimaging applications.

Controlled Synthesis of Ultrathin Lanthanide Oxide Nanosheets and Their Promising pH‐Controlled Anticancer Drug Delivery

Various lanthanide oxides (Sm2 O3 and Gd2 O3 ) nanostructures were synthesized by a facile hydrothermal method. The loss of surfactants on the nanocrystals surface, followed by the resultant assembly is responsible for the formation of ultrathin nanosheets. Owing to strong surface effects, the different morphologies of the Sm2 O3 :5 % Eu and Gd2 O3 :5 % Eu nanocrystals present unique photoluminescence properties. As a proof-of-concept application, the as-obtained Sm2 O3 and Gd2 O3 ultrathin nanosheets exhibit promising pH-controlled anticancer drug-delivery behavior.

Photo-crosslinked fabrication of novel biocompatible and elastomeric star-shaped inositol-based polymer with highly tunable mechanical behavior and degradation.

Biodegradable and star-shaped polymers with highly tunable structure and properties have attracted much attention in recent years for potential biomedical applications, due to their special structure. Here, inositol-based star-shaped poly-L-lactide-poly(ethylene glycol) (INO-PLLA-PEG) biomedical polymer implants were for the first time synthesized by a facile photo-crosslinking method. This biomaterials show controlled elastomeric mechanical properties (~18 MPa in tensile strength, ~200 MPa in modulus, ~200% in elongation), biodegradability and osteoblasts biocompatibility. These results make INO-PLLA-PEG implants highly promising for bone tissue regeneration and drug delivery applications.

Monodispersed Bioactive Glass Nanoclusters with Ultralarge Pores and Intrinsic Exceptionally High miRNA Loading for Efficiently Enhancing Bone Regeneration

Bioactive glass nanoparticles (BGNs) have attracted much attention in drug delivery and bone tissue regeneration, due to the advantages including biodegradation, high bone-bonding bioactivity, and facile large-scale fabrication. However, the wide biomedical applications of BGNs such as efficient gene delivery are limited due to their poor pore structure and easy aggregation. Herein, for the first time, this study reports novel monodispersed bioactive glass nanoclusters (BGNCs) with ultralarge mesopores (10-30 nm) and excellent miRNA delivery for accelerating critical-sized bone regeneration. BGNCs with different size (100-500 nm) are fabricated by using a branched polyethylenimine as the structure director and catalyst. BGNCs show an excellent apatite-forming ability and high biocompatibility. Importantly, BGNCs demonstrate an almost 19 times higher miRNA loading than those of conventional BGNs. Additionally, BGNCs-miRNA nanocomplexes exhibit a significantly high antienzymolysis, enhance cellular uptake and miRNA transfection efficiency, overpassing BGNs and commercial Lipofectamine 3000. BGNCs-mediated miRNA delivery significantly improves the osteogenic differentiation of bone marrow stromal stem cells in vitro and efficiently enhances bone formation in vivo. BGNCs can be a highly efficient nonviral vector for various gene therapy applications. The study may provide a novel strategy to develop highly gene-activated bioactive nanomaterials for simultaneous tissue regeneration and disease therapy.

Biodegradable Multifunctional Bioactive Glass-Based Nanocomposite Elastomers with Controlled Biomineralization Activity, Real-Time Bioimaging Tracking, and Decreased Inflammatory Response

Controlled biomineralization activity of biomaterials is rather important in bone regeneration and osseointegration avoiding the formation of fibrous capsule. However, most of conventional biodegradable elastomeric biomaterials for bone regeneration do not possess biomineralization ability and inherent multifunctional properties. Herein, we report a multifunctional bioactive glass (BG)-based hybrid poly(citrate-siloxane) (PCS) elastomer with intrinsical biomineralization activity and photoluminescent properties for potential bone tissue regeneration. Monodispersed BG nanoparticles (BGNs) were used to control the elastomeric behavior, biomineralization activity, photoluminescent ability, and osteogenic cellular response of PCS elastomers. BGNs significantly enhanced the elastomeric modulus of PCS from 20 to 200 MPa (10 times improvement) and the hydrophilicity (from 82° to 28° in water contact angle). The photoluminescent properties of PCS elastomers were also tailored through the incorporation of BGNs. The in vivo degradation of PCS-BGN nanocomposites could be efficiently tracked through noninvasively monitoring their fluorescent change. PCS-BGN nanocomposites enhanced the proliferation and osteoblastic differentiation of osteoblasts (MC3T3-E1) and decreased the in vivo inflammatory response. This study provided a novel tactics for designing the bioactive elastomeric biomaterials with multifunctional properties for bone regeneration medicine.