Manufacture of PLGA Multiple-Channel Conduits with Precise Hierarchical Pore Architectures and In Vitro/Vivo Evaluation for Spinal Cord Injury

Abstract

By the method of injection molding combined with thermally induced phase separation (TIPS), a novel nerve conduit with a plurality of channels and macro-/microporous architecture was fabricated using poly (lactide-co-glycolide) (PLGA, 75:25; Mn=1.22x10(5)). The diameter of the conduits and the number of channels could be regulated by changing the parameters of the mold, and the porosity of the conduit was as high as 95.4%. Meanwhile, the hierarchical pore architecture of the walls could be controlled through varying the solution concentration and the contents of porogen. The degradation study in vitro showed that 7-channel conduit could hold its apparent geometry for about 12 weeks in phosphate buffer solution (PBS) at 37degreesC, and the pH values of the degradation solution were detected in the range 4.1-4.5. The influences of the conduit architecture on the cell attachment, spreading, and proliferation were evaluated by culturing rat mesenchymal stem cells alone or together with Schwann cells in vitro. The implantation of the PLGA conduit in the spinal cord showed that it had good biocompatibility, and no obvious inflammatory response was detected. Therefore, the results implied that these PLGA multiple-channel nerve conduits have the potential use for spinal cord injury.

Fabrication and Evaluation of PLLA Multichannel Conduits with Nanofibrous Microstructure for the Differentiation of NSCs In Vitro

“…In our previous work, 22 we devised a protocol for the fabrication of poly(lactide-co-glycolide) (PLGA) multichannel conduits with hierarchical pore architectures, including 16 longitudinally aligned channels with 500-1000 mm diameters, 100-200 mm macropores, and 20-50 mm micropores. The method integrated low temperature injection, S-L phase separation, and salt-leaching technologies.…”

“…Considering that the porosity was complementary to the ratio of the porous conduit weight to the theoretical solid conduit weight, the determination of the porosity for the three NCs was completed using the method described previously. 22 The porosity of the NCs includes two parts: the pores in the walls separating the open channels and the channels within the conduit. For the purpose of clarity, V s is defined as the volume of the whole conduit, V c as the volume of the channels, and V w as the volume of walls; D and d are the diameters of the conduit and channels, respectively; l is the length of the conduit; and the number 33 is the number of channels; m is the mass of NC; q is the density of PLLA, which was 1.25 mg/mm 3 .…”

“…The goal of this article was to develop a systematized device to fabricate poly(L-lactide) (PLLA) NCs with both 33 channel-orientation function and ECM biomimetic microstructure on the millimeter and nanometer scales by retrofitting our previous injection mold 22 and adding a heat transfer and nonsolvent exchange system. Two other typical micromorphologies of ladder-like microstructure and macroporous/ nano-wall microstructure in the 33-channel conduits can be constructed conveniently by altering the temperature condition and solvent components of TIPS, using the systematized device, as control.…”

The Application of Stem Cell Based Tissue Engineering in Spinal Cord Injury Repair.

“…Interestingly, the matrix control also had better performance than non-treated control (one subject, scored 6), which indicated the physical support function of scaffold may help to reconstruct local disturbed circuits to regain function [52]. Animal studies with using PLGA and stem cells showed PLGA is an effective cell delivery scaffold with benign cytocompatibility and histocompatibility since it triggers mild immune/inflammation responses but facilitates seeded cells to integrate into host tissue after spinal cord injury [53,54].…”

Biomaterial-based interventions for neuronal regeneration and functional recovery in rodent model of spinal cord injury: A systematic review

“…As shown in Fig. 1, 17 studies were excluded for reasons such as the reports concerned only cell survival/feasibility studies, [44][45][46][47][48][49][50] preliminary or pilot studies, 44-60 the study was not specifically designed to study axonal regeneration after implantation of biopolymer based multimodality intervention, 56,[58][59][60] or a non-biodegradable implant was used in conjunction with the biodegradable scaffold. 55,57 The results are summarized in Table 1.…”