Zongrui Zhang

A Biomimetic Silk Fibroin/Sodium Alginate Composite Scaffold for Soft Tissue Engineering.

A cytocompatible porous scaffold mimicking the properties of extracellular matrices (ECMs) has great potential in promoting cellular attachment and proliferation for tissue regeneration. A biomimetic scaffold was prepared using silk fibroin (SF)/sodium alginate (SA) in which regular and uniform pore morphology can be formed through a facile freeze-dried method. The scanning electron microscopy (SEM) studies showed the presence of interconnected pores, mostly spread over the entire scaffold with pore diameter around 54~532 μm and porosity 66~94%. With significantly better water stability and high swelling ratios, the blend scaffolds crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) provided sufficient time for the formation of neo-tissue and ECMs during tissue regeneration. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) results confirmed random coil structure and silk I conformation were maintained in the blend scaffolds. What’s more, FI-TR spectra demonstrated crosslinking reactions occurred actually among EDC, SF and SA macromolecules, which kept integrity of the scaffolds under physiological environment. The suitable pore structure and improved equilibrium swelling capacity of this scaffold could imitate biochemical cues of natural skin ECMs for guiding spatial organization and proliferation of cells in vitro, indicating its potential candidate material for soft tissue engineering.

Synthesis of polycarbonate urethane elastomers and effects of the chemical structures on their thermal, mechanical and biocompatibility properties

In this study, to obtain biomedical polyurethane elastomers with good mechanical properties and biocompatibility, a series of polycarbonate urethanes were synthesized via a two-step solution of polymerization method using the poly(1,6-hexanediol)carbonate diols (PCDL) as the soft segment, 4,4′-methylenebis(cyclohexyl isocyanate) (H12MDI), 1,6-hexamethylene diisocyanate (HDI) and 1,4-butanediol (BDO) as the hard segment with dibutyltin dilaurate as the catalyst. In this article, we illustrated the physical behaviors were obviously influenced by synthetic routes. And their chemical and physical structures were investigated by gel permeation chromatograph (GPC), differential scanning calorimeter (DSC), fourier transform infrared spectrography (FT-IR) and mechanical properties tests. The surface wettability were studied by contact angle measurement (CA). As a kind of short-term implant biomaterial, the results of the hemolysis and platelet adhesive tests were recorded by spectrophotometer and scanning electron microscopy (SEM), indicating the materials have a great potential for developments and applications in biomedical field.

Flexible silk fibroin films modified by genipin and glycerol

Silk fibroin (SF) films, modified by genipin (GP) and glycerol (Gl), with favourable mechanical properties, were obtained by a casting/solvent evaporation method. Simultaneously, the chemical, mechanical and structural properties of the films were examined and analyzed. Compared to uncrosslinked SF films, fibroin solubility of the modified SF (MSF) and Gl/MSF films in the warm water decreased dramatically from 46% to 15%, exhibiting good stability under a physiological environment. The best, valuable modified films with tensile strength of 18.0 MPa, breaking elongation of 171.1% and Youngs modulus of 463.1 MPa were obtained when the GP and Gl content were both 20 wt% and relative to the amount of fibroin. The deformability of the MSF films augmented significantly by increasing the Gl concentration. Fourier transform infrared (FT-IR) results revealed that GP could react with SF macromolecules to form inter- and intra-molecular conjugated covalent bonds. Moreover, the FT-IR and X-ray diffraction (XRD) studies illustrated the GP induced conformational transition from random coil to β-sheet SF chains, yielding MSF and Gl/MSF films with enhanced stable thermal stability. The cytocompatibility of the MSF films were evaluated through MTT assay using L929 fibroblast. Compared to the SF films treated with 75% ethanol, the MSF films exhibited significant cytocompatibility, which was demonstrated by cell adhesion, proliferation and cell morphology. The intrinsic properties and biological results suggest that the MSF films may be potential candidate materials for wound dressing applications or tissue engineering strategies.

Evaluation on biocompatibility of biomedical polyurethanes with different hard segment contents

In this paper, polyurethane (PU) materials with different contents of hard segment (20%, 25%, 30%) were prepared based on hexamethylene diisocyanate and polycarbonate diols by solution polymerization. The obtained polycarbonate-urethane (PCU) elastomers were characterized by very good hydrophobic property and excellent resistance to hydrolysis. Hemolysis, recalification time and platelet-rich plasma adhesion were used to evaluate the blood compatibility of the materials. L929 cells cultured with leach liquor of these PU membranes were selected to perform the cytotoxicity experiments. The results indicate that the hemolysis rates of PU membranes are all less than 5%, which can meet the requirement of the national standards for biomaterials. However, compared with 20% and 30% groups, the recalification time of the sample containing 25% hard segment is longer, while the number of platelet adhesion is less. Additionally, cells cultured in the leach liquor of PU membranes with 25% hard segment proliferated relatively more thriving, meaning that this proportion of the material has the lowest cytotoxicity.

Paclitaxel-loaded PLGA microspheres with a novel morphology to facilitate drug delivery and antitumor efficiency

The aim of this study was to develop a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS) delivery system to enhance drug delivery and antitumor efficiency as well as reduce drug administration frequency. Therefore, different morphological types of PTX-PLGA-MS were prepared using a modified solvent evaporation technique. Morphology analysis confirmed the successful preparation of the smooth PTX-PLGA-MS with internal sporadic porosity, and the novel rough PTX-PLGA-MS with microporous surface and porous internal structures. The PTX drugs were distributed in the readily bioavailable state (amorphous) in PTX-loaded MS, which allowed fast drug release from MS following intratumoral administration. The drug entrapment and release behaviors indicated that the rough MS could provide enough hydrophobic space for PTX-loading and deep surface folds for fast matrices degradation, thus achieving a higher drug-loading efficiency (17.8%) and a rapid sustained drug release effect. Furthermore, the rough MS showed strengthened in vitro anti-hepatoma efficiency than that of free PTX and smooth MS. The in vivo studies indicated remarkable antitumor activity of rough MS (tumor inhibition rate = 58.33%) for at least 13 days after a single injection, which was because the rapid sustained-release drugs could induce the pro-apoptosis gene and protein expressions, cause extensive tumor cell apoptosis, and reduce the toxicity to normal tissues. In conclusion, the rough PTX-PLGA-MS drug delivery system with outstanding tumor growth inhibition effect could serve as a promising treatment for liver tumor.

Development of a novel morphological paclitaxel-loaded PLGA microspheres for effective cancer therapy: in vitro and in vivo evaluations.

Abstract Sustained release of therapeutic agents into tumor cells is a potential approach to improve therapeutic efficacy, decrease side effects, and the drug administration frequency. Herein, we used the modified double-emulsion solvent evaporation (DSE) method to prepare a novel morphological paclitaxel (PTX) loaded poly(lactide-co-glycolide) (PLGA) microspheres (MS). The prepared rough PTX-PLGA-MS possessed microporous surface and highly porous internal structures, which significantly influenced the drug entrapment and release behaviors. The rough MS with an average particle size of 53.47 ± 2.87 μm achieved high drug loading (15.63%) and encapsulation efficiency (92.82%), and provided a favorable sustained drug release. The in vitro antitumor tests of flow cytometry and fluoroimmunoassay revealed that the rough PTX-PLGA-MS displayed effective anti-gliomas activity and enhanced the cellular PTX uptake through adsorptive endocytosis. Both in vitro and in vivo antitumor results demonstrated that the sustained-release PTX could induce the microtubules assembly and the over-expression of Bax and Cyclin B1 proteins, resulting in the microtubule dynamics disruption, G2/M phase arrest, and cell apoptosis accordingly. Furthermore, as the rough PTX-PLGA-MS could disperse and adhere throughout the tumor sites and cause extensive tumor cell apoptosis with one therapeutic course (12 days), they could reduce the system toxicity and drug administration frequency, thus achieving significant tumor inhibitory effects with rapid sustained drug release. In conclusion, our results verified that the rough PTX-PLGA-MS drug release system could serve as a promising treatment to malignant glioma.

Development and biocompatibility evaluation of biodegradable bacterial cellulose as a novel peripheral nerve scaffold: DEVELOPMENT AND BIOCOMPATIBILITY EVALUATION OF BIODEGRADABLE BACTERIAL CELLULOSE

Peripheral nerve injury is a serious medical problem and severely affects normal life of patient. Bacterial cellulose (BC) is considered as a novel promising biomaterial for tissue engineering, but the poor biodegradability limits its application. In this study, biodegradable bacterial cellulose scaffolds were prepared with different oxidation degrees (O.Ds.) using sodium periodate, evaluating their potential application in peripheral nerve repair. The chemical structure and surface morphology of the oxidized bacterial cellulose (OBC) scaffolds were characterized using Fourier transform infrared spectroscopy, Wide angle X-ray diffraction, and Scanning electron microscope. The porosity, mechanical properties, and degradation behavior of the OBC series scaffolds were extensively examined. Cellular viability and blood compatibility of OBC scaffolds were studied by MTT assay and hemolytic test using Schwann cells (SCs) and red blood cells (RBCs), respectively. The results demonstrated that the biodegradability of OBC scaffolds was improved significantly. OBC scaffolds with lower O.Ds. displayed high porosity with interconnected pores, suitable mechanical property, and biodegradability for peripheral nerve repair. In vitro cytotoxicity and hemolysis test analysis indicated that OBC0.05/3 scaffold is cellular and blood compatible, demonstrating its potential application as a good candidate for peripheral nerve repair.

Synthesis and characterization of serial random and block-copolymers based on lactide and glycolide

The objective of this study is to investigate the properties of poly(lactide-co-glycolide) with different composition ratios and PLGA-PEG-PLGA copolymers synthesized by ring-opening polymerization method. Their compositions, crystallization properties, thermal and degradation behaviors, hydrophilicity and biocompatibility were studied. Our results demonstrate that poly(lactide-co-glycolide) with a 90% lactide and PLGA-PEG-PLGA show some crystallization properties. While as the decrease of lactide content in polymers, poly(lactide-co-glycolide) become amorphous, whereas, their hydrophilicity have been improved on the contrary. Compared to poly(lactide-co-glycolide), the PLGA-PEG-PLGA copolymer has a better hydrophilicity for the existence of polyethylene glycol block. Furthermore, both these polymers display easy controlled degradation properties and good cell compatibility.