Repair and regeneration of the critically injured peripheral nerves is one of the most challenging reconstructive surgeries. Currently available and FDA approved nerve guidance channels (NGCs) are suitable for small gap injuries, and their biological performance is inferior to that of autografts. Development of biomimetic NGCs with clinically relevant geometrical and biological characteristics such as topographical, biochemical and haptotactic cues could offer better regeneration of the long gap complex nerve injuries. Here, in this study, we present the development and preclinical analysis of a 3D printed aligned cryomatrix filled NGCs along with nerve growth factor (NGF) (aCG+NGF) for peripheral nerve regeneration. We demonstrated the application of these aCG+NGF NGCs in the enhanced and successful regeneration of a critically injured rat sciatic nerve in comparison to random cryogel filled NGCs, multichannel, and clinically preferred hollow conduits as well as gold standard autografts. Our results indicated viz-a-viz similar effect of aCG+NGF NGCs to that of autografts, and not only enhanced the overall regenerated nerve physiology, but could also mimic the cellular aspects of regeneration. This study emphasizes the paradigm that these biomimetic 3D printed NGCs will lead to a better functional regenerative outcome under clinical settings.
3-D printing shows great potential in laboratories for making customized labware and reaction vessels. In addition, affordable fused filament fabrication (FFF)-based 3-D printing has successfully produced high-quality and affordable scientific equipment, focusing on tools without strict chemical compatibility limitations. As the additives and colorants used in 3-D printing filaments are proprietary, their compatibility with common chemicals is unknown, which has prevented their widespread use in laboratory chemical processing. In this study, the compatibility of ten widely available FFF plastics with solvents, acids, bases and solutions used in the wet processing of semiconductor materials is explored. The results provide data on materials unavailable in the literature and the chemical properties of 3-D printable plastics that were, are in line with literature. Overall, many 3-D printable plastics are compatible with concentrated solutions. Polypropylene emerged as a promising 3-D printable material for semiconductor processing due to its tolerance of strongly oxidizing acids, such as nitric and sulfuric acids. In addition, 3-D printed custom tools were demonstrated for a range of wet processing applications. The results show that 3-D printed plastics are potential materials for bespoke chemically resistant labware at less than 10% of the cost of such purchased tools. However, further studies are required to ascertain if such materials are fully compatible with clean room processing.
Additive manufacturing (AM) techniques, such as stereolithography (SLA), enable the preparation of designed complex structures. AM has gained interest especially in the tissue engineering field due to the possibility to manufacture patient specific implants. However, AM could be useful also in controlled drug release applications, since the size and shape of the device, pore architecture and surface to volume ratio can be accurately designed. In this study, SLA was used to prepare polycaprolactone scaffold structures containing the model drug lidocaine. The release of lidocaine was studied and the influence of porosity and surface to volume ratio of structures to the drug release was analyzed. Porous samples released lidocaine faster compared to solid ones, whereas the degree of porosity and surface to volume ratio did not have a clear effect on the drug release profile.
Most synthetic bone grafts are either hard and brittle ceramics or paste-like materials that differ in applicability from the gold standard autologous bone graft, which restricts their widespread use. Therefore, the aim of the study was to develop an elastic, highly porous and biodegradable β-tricalciumphosphate/poly(Llactide-co-ε-caprolactone) (β-TCP/PLCL) composite for bone applications using supercritical CO 2 foaming. Ability to support osteogenic differentiation was tested in human adipose stem cell (hASC) culture for 21 d. Biocompatibility was evaluated for 24 weeks in a rabbit femur-defect model. Foamed composites had a high ceramic content (50 wt%) and porosity (65-67 %). After 50 % compression, in an aqueous environment at 37 °C, tested samples returned to 95 % of their original height. Hydrolytic degradation of β-TCP/PLCL composite, during the 24-week follow-up, was very similar to that of porous PLCL scaffold both in vitro and in vivo. Osteogenic differentiation of hASCs was demonstrated by alkaline phosphatase activity analysis, alizarin red staining, soluble collagen analysis, immunocytochemical staining and qRT-PCR. In vitro, hASCs formed a pronounced mineralised collagen matrix. A rabbit femur defect model confirmed biocompatibility of the composite. According to histological Masson-Goldner's trichrome staining and micro-computed tomography, β-TCP/PLCL composite did not elicit infection, formation of fibrous capsule or cysts. Finally, native bone tissue at 4 weeks was already able to grow on and in the β-TCP/PLCL composite. The elastic and highly porous β-TCP/PLCL composite is a promising bone substitute because it is osteoconductive and easy-to-use and mould intraoperatively.
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