Ectopic osteochondral formation of biomimetic porous PVA‐n‐HA/PA6 bilayered scaffold and BMSCs construct in rabbit

Abstract

In this work, the novel poly vinyl alcohol/gelatin-nano-hydroxyapatite/polyamide6 (PVA-n-HA/PA6) bilayered scaffold with biomimetic properties for articular cartilage and subchondral bone is developed. Furthermore, when these osteochondral scaffolds were seeded with induced bone mesenchymal stem cells (BMSCs) and implanted at ectopic sites, showed the potential for an engineered cartilage tissue and the corresponding subchondral bone. BMSCs were expanded in vitro and induced to chondrogenic or osteogenic potential by culturing in suitable media for 14 days. Subsequently, these induced cells were seeded into PVA-n-HA/PA6 separately, and the constructs were implanted into the rabbit muscle pouch for upto 12 weeks. Ectopic neocartilage formation in the PVA layer and reconstitution of the subchondral bone which remained confined within the n-HA/PA6 layer with the alteration of the cellular phenotype were identified with Masson's trichrome stain. Simultaneously, the RT-PCR results confirmed the expression of specific extracellular matrix (ECM) markers for cartilaginous tissue, such as collagen type II (Col-II), or alternatively, markers for osteoid tissue, such as collagen type I (Col-I) at the corresponding layers. During ectopic implantation, the underlying subchondral bone layer was completely integrated with the cartilage layer. The result from the ectopic osteochondral scaffolds implantation suggests that PVA-n-HA/PA6 with induced BMSCs is a possible substitute with potential in cartilage repair strategies.

Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces

“…Recently, bilayered scaffolds have been investigated, where each layer of the scaffold represents a different tissue. [54][55][56] Although a better representation of the complex interface tissue, this strategy does not account for the interface region. [19] More recently, multi-layered scaffolds consisting of three or more layers have been designed.…”

“…[80] In another study, an unconventional approach was taken by combining nHAp and polyamide 6 (nHAp/PA6) with polyvinyl alcohol/gelatin scaffolds to yield a biphasic scaffold. [55] The polyamide amalgamation aided in an increased stiffness and mimicked mineral structures of native bone tissue, thereby integrating with the osteochondral structure following implantation. A common issue associated with most of the autologous implantation protocols is the chondrocyte extraction from the donor, which can lead to donor-site morbidity and cellular dedifferentiation and accrued damage.…”

Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration

“…Very recently, a poly vinyl alcohol/gelatin-nano-hydroxyapatite/polyamide6 (PVA-n-HA/PA6) bilayered scaffold seeded with induced bone marrow stem cells (BMSCs) showed ectopic neocartilage formation in the PVA layer and reconstitution of the subchondral bone, confined within the n-HA/PA6 layer, when implanted into the rabbit muscle pouch for up to 12 weeks [82]. A biphasic scaffold combining hyaluronic acid and atelocallagen for the chondral phase and combining HA and b-TCP for the osseous phase has proved to be effective for repairing osteochondral defects, when implanted in the knee joint of a porcine model [41].…”

Osteochondral regeneration by a bilayered construct in a cell-free or cell-based approach

“…Each layer was cultured in either a chondrogenic or an osteogenic medium to differentiate cells towards cartilage or bone lineages, respectively, for 3 weeks before suturing. Qu et al (2011) developed poly vinyl alcohol/ gelatin-nano-hydroxyapatite/polyamide 6 bilayered scaffolds. The scaffolds were seeded with induced bone mesenchymal stem cells (BMSCs), which were cultured in chondrogenic or osteogenic medium separately for 2 weeks.…”