Biomimetic gradient scaffold of collagen–hydroxyapatite for osteochondral regeneration

Abstract

Osteochondral defects remain a major clinical challenge mainly due to the combined damage to the articular cartilage and the underlying bone, and the interface between the two tissues having very different properties. Current treatment modalities have several limitations and drawbacks, with limited capacity of restoration; however, tissue engineering shows promise in improving the clinical outcomes of osteochondral defects. In this study, a novel gradient scaffold has been fabricated, implementing a gradient structure in the design to mimic the anatomical, biological and physicochemical properties of bone and cartilage as closely as possible. Compared with the commonly studied multi-layer scaffolds, the gradient scaffold has the potential to induce a smooth transition between cartilage and bone and avoid any instability at the interface, mimicking the natural structure of the osteochondral tissue. The scaffold comprises a collagen matrix with a gradient distribution of low-crystalline hydroxyapatite particles. Physicochemical analyses confirmed phase and chemical compositions of the gradient scaffold and the distribution of the mineral phase along the gradient scaffold. Mechanical tests confirmed the gradient of stiffness throughout the scaffold, according to its mineral content. The gradient scaffold exhibited good biological performances both in vitro and in vivo. Biological evaluation of the scaffold, in combination with human bone-marrow–derived mesenchymal stem cells, demonstrated that the gradient of composition and stiffness preferentially increased cell proliferation in different sub-regions of the scaffold, according to their high chondrogenic or osteogenic characteristics. The in vivo biocompatibility of the gradient scaffold was confirmed by its subcutaneous implantation in rats. The gradient scaffold was significantly colonised by host cells and minimal foreign body reaction was observed. The scaffold’s favourable chemical, physical and biological properties demonstrated that it has good potential as an engineered osteochondral analogue for the regeneration of damaged tissue.

In vivo study of polyurethane and tannin-modified hydroxyapatite composites for calvarial regeneration

“… 1 – 3 Most bone defects cannot recover by themselves, bone transplantation is always needed. 2 – 7 Traditional bone defect treatment or bone replacement includes autografts and allografts and the substitute tissues could rapidly osseointegrate with surrounding tissues after implantation. 7 However, conventional bone therapy has encountered limitations such as the threat of bone disease spread, immune response, donor deficiency, and donor site morbidity.…”

“… 7 However, conventional bone therapy has encountered limitations such as the threat of bone disease spread, immune response, donor deficiency, and donor site morbidity. 2 – 8 Alternatively, artificial bone grafts are promising to repair bone defects. Elaborately designed artificial bone grafts should be biocompatible and biodegradable as well as osteoconductive, osteoinductive and angiogenesis promoting, providing temporary and gradually regressive substitutes in the bone defect sites, and actively promote bone regeneration in the degradation process.…”

A Graded, Porous Composite of Natural Biopolymers and Octacalcium Phosphate Guides Osteochondral Differentiation of Stem Cells

“…of introducing four different gradient zones using HA showed improved mechanics. [ 25 ] We followed these ideas in that we used a biopolymer‐ceramic composite rather than collagen alone. It may be also interesting to crosslink the matrix during fabrication.…”

“…[ 8c,21 ] and Parisi et al. [ 25 ] used HA in the bony layer of their collagen‐based osteochondral scaffolds. In our study, we incorporated OCP particles into the chitosan‐collagen blend to further improve bioactivity and biomineralization at the bone layer of the scaffolds.…”

Articular cartilage and osteochondral tissue engineering techniques: Recent advances and challenges

“…Various techniques have been developed to incorporate multiphasic and continuous gradients into the cartilage and osteochondral scaffolds such as 3D printing especially extrusion printing and selective laser sintering [ 130 , 224 , 259 , 260 ], sequential layering of slurry or hydrogel solutions at partial gelation [ 257 , [261] , [262] , [263] ], microfluidic-based method [ [264] , [265] , [266] , [267] , [268] , [269] , [270] , [271] ], electrospinning [ 272 , 273 ], light-mediated hydrogel formation [ 274 , 275 ], centrifugation [ [276] , [277] , [278] ], magnetic field control [ 279 ] and buoyancy-driven approach [ 280 ]. Chemical compositional gradients involve the changes in the fundamental materials and the encapsulated bioactive molecules.…”