Yuzhang Du

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.

Development of Biodegradable Poly(citrate)-Polyhedral Oligomeric Silsesquioxanes Hybrid Elastomers with High Mechanical Properties and Osteogenic Differentiation Activity

Biodegradable elastomeric biomaterials have attracted much attention in tissue engineering due to their biomimetic viscoelastic behavior and biocompatibility. However, the low mechanical stability at hydrated state, fast biodegradation in vivo, and poor osteogenic activity greatly limited bioelastomers applications in bone tissue regeneration. Herein, we develop a series of poly(octanediol citrate)-polyhedral oligomeric silsesquioxanes (POC-POSS) hybrids with highly tunable elastomeric behavior (hydrated state) and biodegradation and osteoblasts biocompatibility through a facile one-pot thermal polymerization strategy. POC-POSS hybrids show significantly improved stiffness and ductility in either dry or hydrated conditions, as well as good antibiodegradation ability (20-50% weight loss in 3 months). POC-POSS hybrids exhibit significantly enhanced osteogenic differentiation through upregulating alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenic markers (ALPL, BGLAP, and Runx2). The high mechanical stability at hydrated state and enhanced osteogenic activity make POC-POSS hybrid elastomers promising as scaffolds and nanoscale vehicles for bone tissue regeneration and drug delivery. This study may also provide a new strategy (controlling the stiffness under hydrated condition) to design advanced hybrid biomaterials with high mechanical properties under physiological condition for tissue regeneration applications.

Development of silica grafted poly(1,8-octanediol-co-citrates) hybrid elastomers with highly tunable mechanical properties and biocompatibility

Biodegradable elastomers are attractive in soft tissue regeneration due to their biomimetic viscoelastic properties and biocompatibility. However, conventional elastomers are inherently weak and lack the bioactivity required for highly efficient tissue regeneration. Silica-based biomaterials have shown high mechanical stiffness and special bioactivities including stimulating osteogenesis and angiogenesis by enhancing corresponding gene expressions. Here, by a facile polymerization, we synthesized a series of silica grafted poly (1,8-octanediol-co-citrate) (SPOC) hybrid elastomers with highly tunable physicochemical properties and bioactivities. The silica phase was successfully grafted to the side chain of POC. The silica phase incorporation significantly endowed POC elastomers with highly controlled thermal stability, mechanical properties, hydrophilicity, biodegradation and biocompatibility. The tensile strength, initial modulus and elongation of SPOC hybrid elastomers were highly tunable and range from 2-15 MPa, 4-25 MPa and 50-140% respectively, which is almost a four-fold enhancement compared with pure POC elastomers. In addition, SPOC elastomers significantly enhanced the proliferation and metabolic activities of multiple cell lines including the adipose-derived stem cells, fibroblasts, myoblasts and osteoblasts, indicating their high biocompatibility. These optimized structures and properties of the silica-grafted hybrid elastomers make them promising for soft and hard tissue regeneration applications.

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.

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.

Development of strong, biodegradable and highly elastomeric polycitrate-gelatin hybrid polymer with enhanced cellular biocompatibility

Native human tissues possess incomparable biological performance due to their strong and viscoelastic mechanical properties, and biocompatible compositions. Herein, by a thermal polymerization and solvent hybridization method, we develop biomimetic polycitrate-gelatin hybrid polymers (PC-GT) with strong mechanical properties and tailored elastomeric behavior for tissue regeneration applications. The incorporation of gelatin significantly enhanced the mechanical properties and cellular biocompatibility of PC. PC-GT hybrids demonstrated the 135 times (from 7.5 to 1015MPa) and 11 times (from 4 to 46MPa) improvement for the elastomeric modulus and tensile strength respectively as compared with PC elastomers, while showing controlled stretchable and elastomeric behavior. In addition, PC-GT hybrids significantly improved the fibroblasts (L929) attachment and proliferation, suggesting their high biocompatibility. This study may provide a novel strategy to design biocompatible hybrid polymers with strong and elastomeric behavior for tissue regeneration and stretchable electronic devices applications.

Long-term real-time tracking live stem cells/cancer cells in vitro/in vivo through highly biocompatible photoluminescent poly(citrate-siloxane) nanoparticles

Long-term live cell tracking is desirable and necessary to understand the dynamics and complexity of biological interactions in stem cells and cancer cells. Conventional live cells fluorescence trackers are generally non-degradable and are showing increased toxicity concerns during the long-term application. Previously we developed biodegradable fluorescent poly(citrate)-based hybrid elastomers for bone regeneration applications. Here, we fabricated the photoluminescent poly(citrate-siloxane) nanoparticles (PCSNPs) through an oil/water emulsion method and demonstrated their long-term live stem cells/cancer cells imaging applications. PCSNPs showed a uniform size distribution (mean diameter 120 nm) and highly stable dispersability (above 30 days) in various physiological medium, as well as excellent fluorescent properties and photostability. PCSNPs possess excellent cellular biocompatibility, which could be efficiently internalized by cells and selectively image the cell lysosome with a high photostability. Compared with commercial Cell Tracker™ Green and Cell Tracker™ Red, the adipose-derived mesenchymal stem cells or human hepatoma cells were stably labeled by PCSNPs for over 14 days as they grew and developed (7 passages). Additionally, PCSNPs efficiently tracked cells up to 7 days in vivo through a non-invasively way compared with 1 day of commercial tracker. This study demonstrates an important strategy to design biodegradable multifunctional delivery platforms for biomedical applications such as long-term bioimaging.