An innovative technique combining phase transition and microprinting in one step was applied to fabricate the nerve conduits used in peripheral nerve regeneration. The asymmetric microporosity served to generate asymmetric permeability, and the surface microgrooves were introduced to achieve cell alignment in vitro. The symmetric/asymmetric porous poly(D,L-lactide) (PLA) substrates with microgrooves on the surface were tested for their ability to repair 10 mm sciatic nerve transection defects in rats. The in vivo results showed that porous PLA conduits maintained a stable supporting structure during the entire regeneration process. The myelin sheaths of the regenerated nerve in asymmetric conduits were thicker than in symmetric groups at 4 weeks. Moreover, the regenerated nerves in the asymmetric conduits with surface microgrooves had the highest degree of myelination at 4 weeks and the most number of vessels at 6 weeks. The walking track analysis also implied that the asymmetric conduits with surface microgrooves had the highest degree of functional recovery. Based on the study, the combination of microgrooves and asymmetric microporous structure could be employed in the design of nerve conduits for peripheral nerve regeneration in the future.

Cell alignment plays an important role in the repair of damaged peripheral nerves. The aligned Schwann cells could direct the axonal outgrowth during nerve reconstruction. One way of aligning Schwann cells is to use surface grooves in micrometric dimensions. In this study, microgrooves on chitosan or poly(D,L-lactide) (PLA) were fabricated and the behaviors of Schwann cells and glial cell line C6 on these surfaces were examined. It was found that Schwann cells and C6 cells could be successfully aligned by the microgrooves, and express the genes related to the production of neurotrophic factors. The polymer conduits with microgrooves on the inner surface were implanted in rats to repair the damaged sciatic nerve. The microgrooved conduits were demonstrated to enhance peripheral nerve regeneration as compared to the smooth conduits.

Nerve conduits are often used in combination with bioactive molecules and stem cells to enhance peripheral nerve regeneration. In this study, the acidic fibroblast growth factor 1 (FGF1) was immobilized onto the microporous/micropatterned poly (D, L-lactic acid) (PLA) nerve conduits after open air plasma treatment. PLA substrates grafted with chitosan in the presence of a small amount of gold nanoparticles (nano Au) showed a protective effect on the activity of the immobilized FGF1 in vitro. Different conduits were tested for their ability to bridge a 15 mm critical gap defect in a rat sciatic nerve injury model. Axon regeneration and functional recovery were evaluated by histology, walking track analysis and electrophysiology. Among different conduits, PLA conduits grafted with chitosan-nano Au and the FGF1 after plasma activation had the greatest regeneration capacity and functional recovery in the experimental animals. When the above conduit was seeded with aligned neural stem cells, the efficacy was further enhanced and it approached that of the autograft group. This work suggested that microporous/micropatterned nerve conduits containing bioactive growth factors may be successfully fabricated by micropatterning techniques, open plasma activation, and immobilization, which, combined with aligned stem cells, may synergistically contribute to the regeneration of the severely damaged peripheral nerve.

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Background Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of 188 Re-labeled nanoliposomes ( 188 Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated. Methods Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188 Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188 Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM ® computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188 Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared. Results In biodistribution, the highest uptake of 188 Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of 188 Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of 188 Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the 188 Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with 188 Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU). Conclusion The use of 188 Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that 188 Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.