Augmentation of engineered cartilage to bone integration using hydroxyapatite

Abstract

Articular cartilage injuries occur frequently in the knee joint. Photopolymerizable cartilage tissue engineering approaches appear promising; however, fundamentally, forming a stable interface between the subchondral bone and tissue engineered cartilage components remains a major challenge. We investigated the utility of hydroxyapatite (HA) nanoparticles to promote controlled bone-growth across the bone-cartilage interface in an in vitro engineered tissue model system using bone marrow derived stem cells. Samples incorporated with HA demonstrated significantly higher interfacial shear strength (at the junction between engineered cartilage and engineered bone) compared with the constructs without HA (p < 0.05), after 28 days of culture. Interestingly, this increased interfacial shear strength due to the presence of HA was observed as early as 7 days and appeared to have sustained itself for an additional three weeks without interacting with strength increases attributable to subsequent secretion of engineered tissue matrix. Histological evidence showed that there was ∼7.5% bone in-growth into the cartilage region from the bone side. The mechanism of enhanced engineered cartilage to bone integration with HA incorporation appeared to be facilitated by the deposition of calcium phosphate in the transition zone. These findings indicate that controlled bone in-growth using HA incorporation permits more stable anchorage of the injectable hydrogel-based engineered cartilage construct via augmented integration between bone and cartilage.

Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces

“…[81] Limited characterization of the bone region. [81] Silk Fibroin and nCaP or nHAp Silk Fibroin Bilayered scaffolds exhibited increased stability and promoted bone growth and formation of blood vessels.…”

“…[81] Limited characterization of the bone region. [81] Silk Fibroin and nCaP or nHAp Silk Fibroin Bilayered scaffolds exhibited increased stability and promoted bone growth and formation of blood vessels. [56,86,87] Trilayered scaffolds demonstrated potential for promoting cell differentiation [90] Long-term in vivo stability remains to be evaluated.…”

“…When tested in vivo, the scaffold integrated well with the host bone tissue and demonstrated superior strength, attributed to the addition of hydroxyapatite. [81] In a similar approach, nHAp was incorporated in PLGA scaffolds using thermal phase separation. [33] The introduction of nHAp to the PLGA scaffold increased the compressive modulus from 400 kPa to 600 kPa.…”

“…[55] Recently, an osteochondral scaffold using agar and poly (ethylene glycol) diacrylate (PEGDA) reinforced with nHAp was fabricated. [81] For the bone region, 2% agar loaded with osteoblasts was selected and the cartilaginous phase was fabricated from 15% PEGDA and 0.5% nHAp (pretreated with growth factors) loaded with mesenchymal stem cells. Finally, a thin stainless steel pin was inserted through the center of scaffold in order to assemble the regions as an osteochondral plug.…”

The effect of interface microstructure on interfacial shear strength for osteochondral scaffolds based on biomimetic design and 3D printing

“…However, the integration of biphasic osteochondral scaffolds reported to date was mainly enhanced by suturing [2], gluing [4,5] or crosslinking [6] and the integration failed to meet the need of osteochondral scaffolds. Recently, incorporation of calcium phosphate compounds such as CPP (calcium polyphosphate) [7], HA (hydroxyapatite) [8] or β-GP (β-glycerophosphate) [9] was reported to promote the interface strength via biological bonding [10] over time, the interface shear strength was still two or three orders of magnitude less than the native tissue [3,9].…”