Fabrication And Properties Of Gelatin Based Bioelastomer And Biomedical Membranes

Elastomer is an important strategy material. Synthetic elastomers are fabricated mainly based on petrochemical products which are non-renewable. It’s important to develop bio-based elastomeric material. Gelatin, as a natural protein extracted from animal, has good biocompatibility and biodegradability. Based on the aim of biomedical application, gelatin based bioelastomer and nancomposites were fabricated by placticized with glycerol. The mechanism of plasticization was studied. The structure and properties of gelatin based nanocomposites were investigated. Furthermore, aiming at developing biomedical membranes especially guided tissue membrane and anti-adhesion membrane, drug loaded nanofiber membranes were fabricated by electro spinning method. The in vitro and in vivo properties of the membranes were characterized to find out the optimal membrane with good treatment efficiency. The development of gelatin based material can not only solve the waste problem of gelatin but also open up new materials application pathway while the material is biodegradable and renewable, realizing the vision and purpose of "Green Chemistry"-"From nature, green fabrication, go back to nature".In the first part, gelatin based bio-elastomer was fabricated by adding high content of glycerol as plasticizer. The mechanism of plasticization was studied by analyzing the microstructure of gelatin and glycerol in the elastomer. Glycerol molecules formed hydrogen bonds with gelatin macromolecules and decreased the interaction among gelatin macromolecules. The physical-chemical, mechanical and processability of the elastomer was influenced by the glycerol content. The elastomer with 100 phr and 150 phr glycerol showed better performance than elastomer with other content of glycerol. During the staying process, aging phenomena of the gelatin elastomer occurred because of the aggregation and self-assemble of gelatin macromolecular chains, resulting in the change of mechanical properties of the elastomer. By crosslinking with genipin, the mechanical property and water resistance of the elastomer were improved with no cytotoxicity. The gelatin elastomer with 100 phr and 150 phr glycerol possessed better property than elastomer with other content of glycerol.To improve the mechanical properties of the gelatin based elastomer and develop functionality of the elastomer, different kind of additives including nano silica, nano hydroxyapatite, halloysite tubes, bioactive glass were added in the gelatin elastomer separately to fabricate gelatin based nanocomposites. The structure and properties of gelatin based nanocomposites were investigated. Gelatin matrix and the nanoparticles with different morphology had good interaction. Nanoparticles dispersed well in the gelatin matrix.Anti-infection drug-loaded GTR membranes with different polymer matrix were fabricated by electrospinning. Metronidazole (MNA), an antibiotic, was successfully incorporated into electrospun nanofibers at different concentrations (0,1,5,10,20,30, and 40 wt% polymer). To obtain the optimum anti-infection membrane, we systematically investigated the properties of the nanofiber membranes including PCL-MNA nanofiber membrane, PG-MNA micro-nanofiber membrane and homogeneous PGH-MNA nanofiber membrane. The interaction between PCL and MNA was identified by molecular dynamics simulation. The dispersion of drug in the fibers, the physical-chemical and mechanical properties of the nanofiber membranes with different drug contents, the barrier function, drug release profiles, antibacterial function, biodegradability and biocompatibility of the membranes were investigated. By comparing the comprehensive properties of the electrospun membranes, drug loaded membranes were effective in preventing the colonization of bacteria and infection. The biodegradation rate of the membranes could be tailored by changing the ratio of PCL and gelatin in the matrix to match the regeneration rate of different patients and different type of tissues.Electrospun PCL/gelatin hybrid membranes were fabricated to be planted at decompressive craniectomy for preventing adhesion formation and facilitating subsequent cranioplasty. We prepared poly (ε-caprolactone)-gelatin (PG) nanofiber membranes with different PCL/gelatin ratios. The architectural features, mechanical properties, cell barrier functions, in vivo degradability, biocompatibility and anti-adhesion function were investigated. All membranes were found to have high tensile strength, and the strength of the membranes improved with the PCL content increased. All the PG membranes presented good biocompatibility and cell isolation performances while increase of gelatin content resulted to enhanced cells adhesion and proliferation.6 months subcutaneous implantation demonstrated that all the membranes showed good histocompatibility and adjustable biodegradation speed. In rabbit cranial defects model, no adhesions were observed, either between the PG membranes and the dura, or between the membranes and the temporal muscle after 1 month implantation. PG membranes’anti-adhesive properties and biodegradable characteristics make it useful as a dural onlay for craniotomy in which a second surgery is planned.Guided tissue regeneration/guided bone regeneration membranes with sustained drug delivery were developed by electrospinning drug-loaded halloysite clay nanotubes doped into poly(caprolactone)/gelatin microfibers. The 20 wt.% of nanotube content in fiber membranes allowed for 25 wt.% metronidazole drug loading in the membrane. Nanotubes with a diameter of 50 nm and a length of 600 nm were aligned within the 400-nm diameter electrospun fibers, resulting in membranes with doubling of tensile strength along the collector rotating direction. The halloysite-doped membranes acted as barrier against cells ingrows and have good biocompatibility. The metronidazole loaded halloysite nanotubes incorporated in the microfibers allowed for extended release of the drugs over twenty days, compared to four days when directly admixed into the microfibers. The sustained release of metronidazole from the membranes prevented the colonization of anaerobic Fusobacteria while Eukaryotic cells could still adhere to and proliferate on the drug-loaded composite membranes. This indicates the potential of halloysite clay nanotubes as drug containers that can be incorporated into electrospun membranes for clinical applications.Biomimetic surface modification of electrospun PCL nanofiber membrane was demonstrated. Drug was covalently grafted on the surface of the nanofiber membrane to fabricate enzyme sensitive drug release. We used dopamine self-polymerization to form thin poly(dopamine) film on the surface of PCL nanofibers in a dopamine solution. Hydroxyl groups were introduced on the surface of the nanofibers. Silane (KH550) grafting as the carried out on the surface of the poly(dopamine)-coated PCL nanofibers to introduce amine groups. A ester has been synthesized from acryloyl chloride and metronidazole. Then drug was grafted on the surface of the nanofiber from C=C on the eater and the amine groups on the nanofibers by means of Michael addition reaction. The modification process of the nanofibers was characterized by SEM, IR, EDS and XPS. Drug released from the surface of the nanofibers by the action of enzyme. The membranes showed enzyme sensitive drug release kinetics with no cytotoxicity.