The Complexity of Joint Regeneration: How an Advanced Implant could Fail by Its In Vivo Proven Bone Component

Abstract

Articular cartilage damage is a major challenge in healthcare due to the lack of long-term repair options. There are several promising regenerative implant-based approaches for the treatment, but the fixation of the implant remains a significant challenge. This study evaluated the potential for repair of an osteochondral implant produced through a novel combined bioprinting-based chondral-bone integration, with and without cells, in an equine model. Implants consisted of a melt electrowritten polycaprolactone (PCL) framework for the chondral compartment, which was firmly integrated with a bone anchor. The bone anchor was produced by extrusion-based printing of a low-temperature setting bioceramic material that had been proven to be effective for osteo-regeneration in an orthotopic, non-load bearing and non-articular site in the same species in an earlier in vivo study. Articular cartilage-derived progenitor cells were seeded into the PCL framework and cultured for 28 days in vitro in the presence of bone morphogenetic protein-9 (BMP-9), resulting in the formation of abundant extracellular matrix rich in glycosaminoglycans (GAGs) and type II collagen. The constructs were implanted in the stifle joints of Shetland ponies with cell-free scaffolds as controls. Clinical signs were monitored, and progression of healing was observed non-invasively through radiographic examinations and quantitative gait analysis. Biochemical and histological analyses 6 months after implantation revealed minimal deposition of GAGs and type II collagen in the chondral compartment of the defect site for both types of implants. Quantitative micro-computed tomography showed collapse of the bone anchor with low volume of mineralized neo-bone formation in both groups. Histology confirmed that the PCL framework within the chondral compartment was still present. It was concluded that the collapse of the osteal anchor, resulting in loss of the mechanical support of the chondral compartment, strongly affected overall outcome, precluding evaluation of the influence of BMP-9 stimulated cells on in vivo cartilage regeneration.

Potential of Melt Electrowritten Scaffolds Seeded with Meniscus Cells and Mesenchymal Stromal Cells

“…By using a custom-made compression head, the complete wedge underwent compression. Surface roughness was not assessed in this study, but previous in vivo studies using fibres of comparable thickness deposited using MEW showed no damage to the opposing structures in the joint ([ 37 ]). Lastly, overall tissue formation was limited in this study, which might be attributed to the low cell numbers, static culture conditions and absence of growth factor stimulation.…”

“…PCL fibres are still present 6 months after implantation in and equine joint after extensive loading. This suggests suitability of the PCL scaffolds for clinical usage [ 37 ].…”

Ponies, Joints, Complexity and the Method of Indifference

“…In their experiment Diloksumpan et al (2021) artificially damaged cartilage by drilling a hole in the joints of ponies, filled the gap with the construct that bears the cultured cartilage, and watched the outcome. To evaluate the results an admirable battery of well-chosen methods was applied to monitor the changes in biomechanical properties, biochemical composition (analysis of collagen and glycosaminoglycans), and morphology of the joints (radiography, microcomputed tomography, histology, and immunohistochemistry), and their function was established by following the walking behavior (gait analysis) of the ponies.…”

“…The paper by Diloksumpan et al (2021) in this issue of JOTE is a good example of this novel approach. The authors are involved in a study of the repair of damage of cartilage in bones and joints, using 3D-printed constructs; these serve as a scaffold on top of which new cartilage that has been grown in a cell culture system may be implanted inside the damaged site, leading to newly-formed cartilage growing from the implant.…”

The Importance of Interfaces in Multi‐Material Biofabricated Tissue Structures

“…While tested in vivo in a horse, results demonstrated successful mechanical stability and integration with surrounding native cartilage and bone tissues. [148] This interesting converged bioprinting and biomaterials approach shows promise for engineering mechanical competent soft-hard tissue interfaces. [147] Thus, we have exemplified how the combination of fiber or filament reinforcing technologies with extrusion based biofabrication techniques has proven to be an useful fabrication approach for the realization of 3D constructs that can approximate to the structural and mechanical functionality of native tissues.…”