Challenges in engineering osteochondral tissue grafts with hierarchical structures

Abstract

Introduction A major hurdle in treating osteochondral (OC) defects are the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct-engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. Areas covered This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. Expert opinion A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens, and harnessing of inflammatory responses of the host will likely drive the further progress.

Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering

“…The application of hiPSCs in OC engineering is also somewhat limited by the current protocols for chondrogenic differentiation that are complicated and inefficient primarily due to the need for intermediate embryoid body (EB) formation, required to generate endodermal, ectodermal, and mesodermal cell lineages [1].…”

“…Importantly, the cartilage engineered in this way possessed physiologic compressive modulus and lubricative property (Young moduli >0.8 MPa, and friction coefficients <0.3). This method could be highly effective for generating human osteochondral tissue constructs, and for repairing focal cartilage defects to replace currently used dissociated chondrogenic cells [1].…”

“…In the ideal scenario, the medium would be perfused through a network of channels with endothelial lining, serving as precursors of the vascular network to connect at a later point to the blood supply of the host. Such bioreactor systems are conceptually biomimetic, since they enable convective-diffusive mass transport similar to that occurring in vivo, between blood and tissue, along with dynamic hydrodynamic shear that is an important regulatory factor for bone development and maintenance [1,96].…”

“…Besides such neotissue engineering for potential clinical use, other applications of biomimetic OC TE include formation of the OC tissues to be used as high fidelity disease/healing models and as in vitro models for drug toxicity/efficacy evaluation [1,2].…”

“…A single heterogenous scaffold for the whole OC construct = scaffolds with morphological/physical gradients 4. A single homogenous scaffold for the whole OC construct = scaffolds with biochemical gradients However, up to now, there was no defined scaffold structure and biomaterial that was able to meet all the necessary requirements for the formation of a native-like OC-tissue [1] which is why the current state-of-the-art approach in OC TE is to use multilayered hybrid scaffolds, with biochemical, structural and mechanical gradients.…”