A Novel Hyaluronate–Atelocollagen/β-TCP–Hydroxyapatite Biphasic Scaffold for the Repair of Osteochondral Defects in Rabbits

Abstract

The authors devised a novel biphasic scaffold combining hyaluronic acid and atelocollagen for the chondral phase and combining hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP) for the osseous phase. The biphasic scaffold was fabricated by placing the freeze-dried chondral phase over the HA/beta-TCP scaffold prewetted with hyaluronate/atelocollagen solution. Chondrocytes were isolated in 28 rabbits, expanded, injected inside the chondral phase of the biphasic scaffold, and then cultured in chondrogenic medium. After 2 weeks of in vitro culture, chondrocytes had evenly infiltrated inside the chondral phase and produced extracellular matrix. For in vivo study, a large osteochondral defect was made on the patellar groove of the right distal femur and managed using one of the following methods: filling with cell-biphasic scaffold composite (group I); implanting only biphasic scaffold (group II); placing the removed osteochondral fragments back into the defect (group III, positive control); leaving empty (group IV, negative control). Seven rabbits were allocated to each group. After 12 weeks, the International Cartilage Repair Society Macroscopic Score was highest in group III, followed by group I, group II, and lastly group IV. Depression of the defect was greatest in group IV. There were three rabbits (two in group I and one in group II) that were completely denuded of the chondral phase. The junction to adjacent native cartilage was distinct in rabbits of all groups. The International Cartilage Repair Society Visual Histological Score was highest in group III, followed by groups II and I, and lastly group IV. In conclusion, our results suggest that a biphasic osteochondral composite using a chondral phase consisting of hyaluronate and atelocollagen and an osseous phase consisting of HA and beta-TCP holds the promise for repair of osteochondral defects.

Simultaneous regeneration of articular cartilage and subchondral bone in vivo using MSCs induced by a spatially controlled gene delivery system in bilayered integrated scaffolds

“…MSCs cultured on scaffold looked round as shown in Fig. 2D and E, which was the same shape as reported [21,22].…”

Repair of large osteochondral defects in a beagle model with a novel type I collagen/glycosaminoglycan-porous titanium biphasic scaffold

“…Multiphasic scaffold design has been researched for osteochondral tissue engineering [6,7,[30][31][32][33][34][35]. Each scaffold has its own limitation.…”

“…Thus, a significant barrier to clinical translation is how to achieve biological fixation or functional integration of the tissue-engineered orthopaedic grafts [46]. Multiphasic scaffold design has been researched for osteochondral tissue engineering [6,7,[30][31][32][33][34][35]. Maehara et al developed a hydroxyapatite/ collagen (HAp/Col) scaffold and investigated the efficacy of porous HAp/ Col impregnated with FGF-2 to repair large osteochondral defects in a rabbit model [34].…”

Osteogenic Differentiation of Human Bone Marrow Stromal Cells in Hydroxyapatite-Loaded Microsphere-Based Scaffolds

“…For bone tissue engineering, approaches have involved the incorporation of calcium-based minerals such as tricalcium phosphate (TCP) [9][10][11][12] and hydroxyapatite (HAp). 10,[13][14][15] The osteoblastic response to HAp is well documented and has been shown to enhance implant integration in vivo.…”

“…10,[13][14][15] The osteoblastic response to HAp is well documented and has been shown to enhance implant integration in vivo. 10,13,16,17 With regard to osteochondral designs, mineral additives are typically isolated to the bone-like side of 3-D scaffolds, yielding stratified or continuously graded designs. Stratified designs exhibit a sharp physical transition between bone-like and cartilage-like regions, whereas continuous gradients employ a smooth transition between scaffolding layers.…”