Integrated Bi‐Layered Scaffold for Osteochondral Tissue Engineering

Abstract

Osteochondral tissue engineering poses the challenge of combining both cartilage and bone tissue engineering fundamentals. In this study, a sphere-templating technique was applied to fabricate an integrated bi-layered scaffold based on degradable poly(hydroxyethyl methacrylate) hydrogel. One layer of the integrated scaffold was designed with a single defined, monodispersed pore size of 38 μm and pore surfaces coated with hydroxyapatite particles to promote regrowth of subchondral bone while the second layer had 200 μm pores with surfaces decorated with hyaluronan for articular cartilage regeneration. Mechanical properties of the construct as well as cyto-compatibility of the scaffold and its degradation products were elucidated. To examine the potential of the biphasic scaffold for regeneration of osteochondral tissue the designated cartilage and bone layers of the integrated bi-layered scaffold were seeded with chondrocytes differentiated from human mesenchymal stem cells and primary human mesenchymal stem cells, respectively. Both types of cells were co-cultured within the scaffold in standard medium without soluble growth/differentiation factors over four weeks. The ability of the integrated bi-layered scaffold to support simultaneous matrix deposition and adequate cell growth of two distinct cell lineages in each layer during four weeks of co-culture in vitro in the absence of soluble growth factors was demonstrated.

Engineering Complex Orthopaedic Tissues Via Strategic Biomimicry

“…Comparable results were obtained from other stem cell-seeded biphasic scaffold designs. 15,32,37,47,103,119 Collectively, these studies demonstrate the feasibility of engineering both cartilage- and bone-like tissues. However, similar to other soft tissue-bone designs discussed above, these biphasic scaffolds are for engineering cartilage and bone, while the osteochondral interface between the two tissues has been underemphasized in these designs.…”

“…Inspired by these multi-tissue structures, a variety of complex scaffold designs seeking to recapitulate the native spatial and compositional inhomogeneity have been developed. 4,28,77 This review will discuss current regenerative engineering efforts in ligament-bone, 3,11,19,20,54,62,68,71,72,86,87,96–98,110,111,113–115 tendon-bone, 24,78,79,137 muscle-tendon, 57,58,60,117,118 and cartilage-bone integration, 1,5,13,15–18,25–27,30,32,33,36,37,39,41,47,49,52,53,55,56,69,74,91,95,100–104,106,119,128,133–136 focusing on biomaterial- and cell-based strategies for engineering biomimetic, functional spatial variations in composition and mechanical properties. In light of the complexity of multi-tissue regeneration, the application of strategic biomimicry across tissue-tissue junctions, or prioritizing what needs to be recapitulated from native tissues and identifying the most crucial parameters for complex scaffold design, is essential for avoiding over-engineering the scaffold system.…”

A biphasic scaffold based on silk and bioactive ceramic with stratified properties for osteochondral tissue regeneration

“…The two phases were well-integrated at a continuous interface to form the coherent structure of the biphasic scaffold, via a simple fabrication method that allowed control over the size of the interface region. The realisation of this biphasic scaffold design therefore circumvented many of the common issues encountered with other integrated scaffold designs featuring stratified layers with heterogeneous properties, including the lack of smooth transition between phases, 38,39,41,42,45,47,49 lack of control over the size of the interface region, 44,48 and complicated or tedious fabrication methods. 42,43 …”

Chitosan-Based Nanofibrous Membrane Unit with Gradient Compositional and Structural Features for Mimicking Calcified Layer in Osteochondral Matrix

“…The major organic materials that are used for building layered scaffolds include collagen, silk fibroin, agarose, hyaluronic acid, and cell-free ECM, as well as some biodegradable synthetic polyester [12,13,14,15,16,17,18,19,20]. In the cases of scaffolds that are used for osteochondral repair, inorganic materials, such as hydroxyapatite, tricalcium phosphate, and bioactive glass are also employed because the calcified layer and subchondral layer of native osteochondral ECM contain various amounts of inorganic matter besides other ingredients, such as proteins and glycosaminoglycans (GAGs) [13,14,16,21,22,23].…”