Osteochondral interface regeneration of the rabbit knee with macroscopic gradients of bioactive signals

Abstract

To date, most interfacial tissue engineering approaches have utilized stratified designs, in which there are two or more discrete layers comprising the interface. Continuously-graded interfacial designs, where there is no discrete transition from one tissue type to another, are gaining attention as an alternative to stratified designs. Given that osteochondral regeneration holds the potential to enhance cartilage regeneration by leveraging the healing capacity of the underlying bone, we endeavored to introduce a continuously graded approach to osteochondral regeneration. The purpose of this study was thus to evaluate the performance of a novel gradient-based scaffolding approach to regenerate osteochondral defects in the New Zealand White rabbit femoral condyle. Bioactive plugs were constructed from poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres with a continuous gradient transition between cartilage-promoting and bone-promoting growth factors. At six and 12 weeks of healing, results suggested that the implants provided support for the neo-synthesized tissue, and the gradient in bioactive signaling may have been beneficial for bone and cartilage regeneration compared to the blank control implant, as evidenced by histology. In addition, the effects of pre-seeding gradient scaffolds with umbilical cord mesenchymal stromal cells (UCMSCs) from the Wharton’s jelly of New Zealand White rabbits were evaluated. Results indicated that there may be regenerative benefits to pre-localizing UCMSCs within scaffold interiors. The inclusion of bioactive factors in a gradient-based scaffolding design is a promising new treatment strategy for defect repair in the femoral condyle.

Microsphere-Based Gradient Implants for Osteochondral Regeneration: a Long-Term Study in Sheep

“…Hence, the current study investigated the potential of implanting gradient scaffolds engineered to recruit stem cells from the bone marrow into large defects for the purpose of regenerating bone and cartilage. We have previously investigated the potential of the microsphere-based scaffolds with gradients of growth factors, raw materials and combinations for both osteochondral tissue engineering in vitro and osteochondral regeneration in vivo in rabbits [10,20,[35][36]. This is our first report on the long-term outcome of the implant of these gradient scaffolds in critical size osteochondral defects (6 mm diameter × 6 mm depth) in a large animal model.…”

Silk scaffolds for dental tissue engineering

“…In 2012, Dormer and co-workers reported the use of a miniature bioactive plug, which was constructed from PLGA microspheres with a gradient transition between chondrogenic and osteogenic growth factors, to repair small mandibular condylar defects in New Zealand white rabbits. After six weeks, histology and magnetic resonance imaging (MRI) showed that the implants provided support for the neosynthesized tissue regeneration within the defects (Dormer et al, 2012). Yu et al (2011) combined distraction ontogenesis with tissue engineered cartilage to reconstruct condylar osteochondral defects in goats.…”

Cartilage-Bone Interface Features, Scaffold and Cell Options for Regeneration

“…The major ECM components contained in these sub-tissues are collagen type II and glycosaminoglycans; collagen type I, glycosaminoglycans, minerals; and collagen type I and minerals, respectively (Table 1). Another school of thought for the hierarchical organization of the cartilage-bone interface is the belief of graded change in the composition of ECM components [6][7][8][9]. Although the compartmental organization approach for cartilage-bone interface components has been dominant for years [5,10], recent studies characterizing cartilagebone, as well as tendon-bone, interface at microscopic dimensions found that mineral composition is changing gradually across the interface [4,11,12].…”