title: Custom-tailored tissue engineered polycaprolactone scaffolds for total disc replacement.
abstract: Degeneration of the intervertebral disc (IVD) represents a significant musculoskeletal disease burden. Tissue engineering has proposed several strategies comprising the use of biodegradable materials to prepare scaffolds that can present mechanical properties similar to those of native IVD tissues. However, this might be insufficient, since the patient's intervertebral space geometry must be replicated to allow for appropriate implant fixation and integration. Herein, we propose the use of reverse engineering and rapid prototyping techniques with the goal of preparing custom-tailored annulus fibrosus scaffolds; these techniques have previously been applied to rabbit models. The IVD reverse-engineered architecture was obtained by means of microcomputed tomography acquisition and three-dimensional modelling, resulting in a computer-aided design (CAD) that replicates the original rabbit IVD. Later, a fused deposition-modelling three-dimensional printer was used to produce the scaffolds with different geometries provided by the CAD, using polycaprolactone (PCL) with 100% infill density. The microstructure of the PCL scaffolds was investigated by scanning electron microscopy (SEM), which allowed us to observe an adequate fusion adhesion between the layers. The SEM images revealed that, up to the point of moderate resolution, the porosities manually designed in the CAD model were successfully replicated. The PCL scaffolds' three-dimensional architecture was also assessed by means of microcomputed tomography analysis. Compressive stiffness was determined using a mechanical testing system. Results showed higher values than those of human IVDs (5.9-6.7 kN mm(-1) versus 1.2 kN mm(-1), respectively). In vitro studies were performed to investigate the possible cytotoxicity of the polycaprolactone scaffolds' leachables. The results showed that the custom-tailored PCL scaffolds do not have any deleterious cytotoxic effect over annulus fibrosus cells or the mouse lung fibroblast's cell line. This study proposed a simple, rapid, and low-cost strategy to fabricate custom-tailored annulus fibrosus scaffolds. In the future, this strategy might be used in association with nucleus pulposus regeneration strategies to facilitate the development of tissue-engineered total disc replacement implants specific to each patient, with a goal of full IVD regeneration.
authors.affiliation: 3B's Research Group-Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal. ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: S
authors.initials: S
authors.lastname: van Uden
authors.forename: J
authors.initials: J
authors.lastname: Silva-Correia
authors.forename: V M
authors.initials: VM
authors.lastname: Correlo
authors.forename: J M
authors.initials: JM
authors.lastname: Oliveira
authors.forename: R L
authors.initials: RL
authors.lastname: Reis
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003198:Computer Simulation; D021621:Imaging, Three-Dimensional; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000187:drug effects / Q000648:ultrastructure; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008422:Materials Testing; D051379:Mice; D011091:Polyesters / Q000494:pharmacology*; D016062:Porosity; D011817:Rabbits; D011859:Radiography; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D059145:Total Disc Replacement
chemical_list: D011091:Polyesters; C016240:polycaprolactone