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.
Nerve guide conduits (NGCs) with geometric design have shown significant advantages in guidance of nerve reinnervation across the defect of injured peripheral nerves. It is realized that intraluminal fillers with distinctive structure can effectively provide an inner guidance for sprouting of axons and improve the permeability of NGC. In this work, a poly(lactic‐co‐glycolic acid) (PLGA) NGC is prepared containing intraluminal sponge fillers (labeled as ISF‐NGC) and used for reconstruction of a rat sciatic nerve with a 10 mm gap. For comparison, the same procedure is applied to a single hollow PLGA NGC (labeled as H‐NGC) and an autologous nerve. As evidenced by significantly improved nerve morphology and function, the ISF‐NGC achieves a superior nerve repair effect over H‐NGC, which is comparable to autologous nerve grafting. It is likely that the H‐NGC only provides a protected tunnel for nerve fiber regrowth and axonal extension, while ISF‐NGC offers an extracellular matrix‐mimetic architecture as autograft to provide contact guidance for nerve reinnervation. This newly developed ISF‐NGC is a promising candidate to aid nerve reinnervation across longer gaps commonly encountered in clinical cases.
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 OBC scaffold is cellular and blood compatible, demonstrating its potential application as a good candidate for peripheral nerve repair. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1288-1298, 2018.
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.
A novel morphological PTX-PLGA-MS with microporous surface and porous internal structures to enhance drug loading, delivery and antitumor efficiency.
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