Abstract
The ability to treat osteochondral defects is a major clinical need. Existing polymer systems cannot address the simultaneous requirements of regenerating bone and cartilage tissues together. The challenge still lies on how to improve the integration of newly formed tissue with the surrounding tissues and the cartilage-bone interface. This study investigated the potential use of different silk fibroin scaffolds: mulberry (Bombyx mori) and non-mulberry (Antheraea mylitta) for osteochondral regeneration in vitro and in vivo. After 4 to 8 weeks of in vitro culture in chondro- or osteo-inductive media, non-mulberry constructs pre-seeded with human bone marrow stromal cells exhibited prominent areas of the neo tissue containing chondrocyte-like cells, whereas mulberry constructs pre-seeded with human bone marrow stromal cells formed bone-like nodules. In vivo investigation demonstrated neo-osteochondral tissue formed on cell-free multi-layer silk scaffolds absorbed with transforming growth factor beta 3 or recombinant human bone morphogenetic protein-2. Good bio-integration was observed between native and neo-tissue within the osteochondrol defect in patellar grooves of Wistar rats. The in vivo neo-matrix formed comprised of a mixture of collagen and glycosaminoglycans except in mulberry silk without growth factors, where a predominantly collagenous matrix was observed. Immunohistochemical assay showed stronger staining of type I and type II collagen in the constructs of mulberry and non-mulberry scaffolds with growth factors. The study opens up a new avenue of using inter-species silk fibroin blended or multi-layered scaffolds of a combination of mulberry and non-mulberry origin for the regeneration of osteochondral defects.
Highlights
Osteochondral defects (OCDs) result from traumatic injuries or natural degradation of cartilaginous tissue with aging and encompass serious damage to articular cartilage and/or underlying calcified subchondral bone [1]
Micro-architecture of 3D silk fibroin network Silk fibroin scaffolds prepared by lyophilization (Figure 1)
Based upon SEM images, these pores varied according to whether the scaffolds were Antheraea mylitta (Am) or Bombyx mori (Bm); pores with more open, interconnected and well defined boundaries were observed in Am, in contrast to Bm
Summary
Osteochondral defects (OCDs) result from traumatic injuries or natural degradation of cartilaginous tissue with aging and encompass serious damage to articular cartilage and/or underlying calcified subchondral bone [1]. Attempts have been made with Ostecel (hydroxyapatite and autologous MSCs), INFUSETM (recombinant human bone morphogenetic protein), VITOSSH (calcium phosphate-bone bonding protein), CORTOSS (synthetic bone void filler) [6] and TruFit (PLGA Plug) [7] as scaffolding materials to regenerate osteo/chondral tissues. Most of these materials are limited for applications in long term sustained tissue regeneration due to their synthetic origin nature, potential to raise inflammatory or foreign body responses in host systems and inconsistent/unacceptable degradation rates accompanying neotissue formation [7,8,9,10]. Silk scaffolds, which acts as a template in regenerative therapeutics for a wide range of tissues, is FDA approved for ligament and tendon repair and commercially marketed by Serica [11]
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