Abstract
Problem:
The generation of tissue-engineered cartilage constructs has made great progress over the last decades, however, the fixation of the grafts to the subchondral bone plate is still an unresolved problem. The aim of this study was to investigate a modular lattice concept as an anchoring basis for biological joint resurfacing that is stably fixed to the subchondral bone, versatile for any surface shape, and permissive for cellular repopulation.
Methods:
Ceramic building blocks (hydroxyapatite, β-tricalcium phosphate, biphasic calcium phosphate, alumina, and bioactive glass), including anchoring pins were fabricated by transfer injection molding technique. The cellular repopulation of the building blocks and cellular differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) was analyzed under the influence of platelet-rich plasma, transforming growth factor-β (TGF-β), and bone morphogenetic protein-2 (BMP-2). A lattice construct of anchoring pins fixed to the subchondral bone specimen and interposed hBMSC within collagen hydrogel was cultured under dynamic conditions in spinner flasks for 4 weeks. The three-dimensional (3D) constructs were analyzed by high-resolution microcomputed tomography, light sheet fluorescence microscopy, and histology. Pin fixation was analyzed by pull-out tests.
Results:
Building block modules of complex shape with anchoring pins can be individually arranged to the subchondral bone by simple press-fit principle. Pull-out tensile stress exceeded 6 MPa. hBMSCs required stimulation by TGF-β or BMP-2 to undergo chondrogenic differentiation. Dynamic culturing of 3D explant constructs demonstrated the stability of the modular lattice construct and the interposed cell-loaded hydrogel remained within the lattice elements. hBMSCs within the collagen hydrogel underwent chondrogenic differentiation and formed a matrix that merged with the lattice structure of building blocks.
Conclusions:
The current work presents a proof-of-principle concept for a lattice structure that provides the stable mechanical bonding and biological milieu for the bone–cartilage interface. The anchoring elements represent an integral part of the lattice structure and provide the basis for future biological joint resurfacing by multilayer constructs.
Impact Statement
The repair of large articular cartilage lesions is still a major challenge. In particular, the fixation of the grafts to the subchondral bone plate represents an unresolved problem. In this work, we present a completely novel concept based on a modular lattice, combining building blocks of different ceramic materials, anchoring pins and space for cell-loaded hydrogels or other scaffold materials. This concept targets not only circumscribed cartilage defects but also large osteoarthritic lesions. It spans the bridge between cell therapy and artificial joint arthroplasty, and thus is of significant medical and socioeconomic impact.
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