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.

Application of a 3D custom printed patient specific spinal implant for C1/2 arthrodesis

“…These latter domains remain an area of interest with numerous studies into different synthesis techniques for implants, and differences in both 3DP material composition and architectural characteristics ongoing. Recent developments into 3DP scaffolds as a total disc replacement substitute are limited to lab-based testing or animal studies (20,21).…”

Insulin immobilized PCL‐cellulose acetate micro‐nanostructured fibrous scaffolds for tendon tissue engineering

“…A PCL-CA blend was chosen to combine the advantages of both synthetic and natural polymers. PCL is a well-characterized polyester for tissue engineering and drug delivery applications 34,[55][56][57] due to its controllable properties. Various methods such as surface modification and formation of PCL composites can result in alterations in the polymer's mechanical properties, degradation, and bioactivity.…”

X-ray computed tomography and additive manufacturing in medicine: a review

“…AM production and implantation of basic personalised implants based on XCT data are now commonplace, and reflecting this, a wide array of studies involving implantation have been published over the past year as the technology has become better understood [106][107][108][109][110][111][112][113][114][115][116][117][118][119]. Clinical usage of metallic implants produced by AM in particular is now becoming common, specifically in maxillofacial and orthopaedic applications, though a number of issues remain preventing further adoption.…”

“…Xu et al [106] produced artificial goat femurs using XCT with FDM of a hydroxyapatite/polycaprolactone (HA/PCL) composite, showing good biocompatibility and bone-analogous load bearing performance in vitro and in vivo, concluding that extension to human patients was viable. Similarly, van Uden et al [114] used XCT data with FDM to create PCL intervertebral disk scaffolds with mechanical properties similar to native tissue. XCT was then performed pre-and post-operatively following implantation into rabbits to analyse porosity and compare implants to the native tissue; in this instance finding the compressive stiffness to be greater than human native tissue.…”