Fabrication and in vitro evaluation of an articular cartilage extracellular matrix-hydroxyapatite bilayered scaffold with low permeability for interface tissue engineering

Abstract

BackgroundOsteochondral interface regeneration is challenging for functional and integrated cartilage repair. Various layered scaffolds have been used to reconstruct the complex interface, yet the influence of the permeability of the layered structure on cartilage defect healing remains largely unknown.MethodsWe designed and fabricated a novel bilayered scaffold using articular cartilage extracellular matrix (ACECM) and hydroxyapatite (HAp), involving a porous, oriented upper layer and a dense, mineralised lower layer. By optimising the HAp/ACECM ratio, differing pore sizes and porosities were obtained simultaneously in the two layers. To evaluate the effects of permeability on cell behaviour, rabbit chondrocytes were seeded.ResultsMorphological observations demonstrated that a gradual interfacial region was formed with pore sizes varying from 128.2 ± 20.3 to 21.2 ± 3.1 μm. The permeability of the bilayered scaffold decreased with increasing compressive strain and HAp content. Mechanical tests indicated that the interface was stable to bearing compressive and shear loads. Accordingly, the optimum HAp/ACECM ratio (7 w/v%) in the layer to mimic native calcified cartilage was found. Chondrocytes could not penetrate the interface and resided only in the upper layer, where they showed high cellularity and abundant matrix deposition.ConclusionsOur findings suggest that a bilayered scaffold with low permeability, rather than complete isolation, represents a promising candidate for osteochondral interface tissue engineering.

A novel nano-composite scaffold for cartilage tissue engineering

“…The presence of 45SBG nanoparticles in the nanocomposite scaffolds could enhanced more cell attachment on the surface of the samples. Therefore, it creates a suitable environment for cultivated cells.This was in agreement with previous studies that they approved the role of Ha and fibrin in providing the good condition for cell viability [40,41]. Current understanding is mainly reported to involve the interaction of stem cells and the nanocomposite scaffolds by motivating various signaling pathways.…”

“…It can be observed that there were no apatite crystals on the surfaces of the pure PLGA samples after 7 days of incubations in SBF and no apatite peaks were found in XRD pattern of such samples.In fact, AC and subchondral bone are the complex structures. From this point of view, as that researchers mentioned, presence of sufficient amount of hydroxyapatite on the surface of regenerative construct could affect cell attachment and mimicing native calcified cartilage and may be considered as a prominent way in order to rehabilitate damaged cartilage [40].…”

Reinforcement of Mono- and Bi-layer Poly(Ethylene Glycol) Hydrogels with a Fibrous Collagen Scaffold

“…A limitation of the present study, and a necessary component in future work, is the lack of experimental evaluation of shear failure of the interface between stiff and soft layers in bi-layered hydrogels 55 . In this study 17% of the single-phase, bi-layer hydrogels subjected to compressive loading exhibited a clear pattern of failure due to shear forces whereas none of the multi-phase materials failed in this manner.…”

“…Instead, we sought inspiration from the native osteochondral interface where collagen fibers extend from the zone of calcified cartilage through the hyaline cartilage to span tissues possessing moduli that vary by several orders of magnitude. These fibers thus serve as a physical anchor and bear loads such that they reduce stress concentrations that might otherwise form at the interface between the two tissues 11, 57, 55 Similarly, our material system enables us to evaluate the effectiveness of a fibrous phase to reduce stress and strain concentrations at the interface of two highly compliant, hydrated materials possessing dissimilar moduli.…”

“…For example, interdiffusion between the two phases prior to processing leads to a continuous interface possessing the compositional make-up of both phases. 24, 55 Templating methods have also been developed to create an abrupt change in pore size, where the polymer phase is continuous across the entire scaffold. 19 Overall, these studies point towards the need for a mechanically robust interface in biphasic scaffolds, particularly when mechanical loads are present and the two, layered phases possess substantially different mechanical properties.…”