A Computational Model of Osteochondral Defect Repair Following Implantation of Stem Cell-Laden Multiphase Scaffolds

Abstract

Tissue engineering (TE) has recently emerged as a potential method with which to treat osteochondral defects. In order to improve these strategies, an understanding is required of how the cells within an implanted scaffold interact with their local environment.To this end, the objective of this study was to develop a computational model of an osteochondral defect following the implantation of a tissue engineered scaffold. In particular, the purpose of this was to systematically explore the relationship that scaffold design has on the spatial formation of cartilage and bone within the defect. In this study, tissue formation was predicted using a previously developed algorithm in which cell fate was dependent upon the local oxygen tension and the local mechanical environment. In the first part of this study, the model was updated to include a condition whereby mature cartilage was resistant to both terminal differentiation and vascularisation. The updated model was then tested by using it to predict tissue formation during the spontaneous repair process within an osteochondral defect. Following this, the model was used to simulate an osteochondral defect treated with different variations of a previously developed multiphasic scaffold. By comparing the results of the different simulations it was possible to elucidate a mechanism by which the scaffold promoted robust bone and cartilage formation. In particular, support was provided for a previous hypothesis which proposed that osteochondral defect repair can be enhanced by actively confining angiogenesis to within the subchondral region of the defect for a sustained period of time. Based on the results of this study, it was possible to expand on this by suggesting that this time period be no less than 10 weeks. It is possible to reduce this, however, by pre-culturing MSCs under chondrogenic conditions prior to implantation within the defect.

Restoration of osteochondral defects by implanting bilayered poly(lactide-co-glycolide) porous scaffolds in rabbit joints for 12 and 24 weeks

“…While the scaffold led to some articular cartilage repair, implantation of a cell-laden bilayered scaffold was found to further increase cartilage formation in the chondral layer of the scaffold. Despite these improvements, the subchondral bone progressed into the chondral regions of these implants by means of endochondral ossification according to the histological observation at the later stage, which led to thinning of the cartilage tissue [42].…”

Regeneration of Osteochondral Defects Using Developmentally Inspired Cartilaginous Templates

“…A previously developed computational model was used to predict BMSC differentiation and tissue development in the empty and treated defect (47,(54)(55)(56). This model utilised an iterative procedure which is outlined in greater detail in a previous study (56). Briefly, a finite element (FE) model was used to determine the mechanical environment within the defect (Fig.…”

Recent Approaches to the Manufacturing of Biomimetic Multi-Phasic Scaffolds for Osteochondral Regeneration

“…Recently, the interest in OC regeneration to manufacture not only bi-phasic but multi-phasic scaffolds in order to mimic better the native OC tissue has been dramatically increasing. [ 33 , 34 ]. One major focus of these multi-phasic scaffolds is the interface between the cartilage and bone tissue, or the layer of the scaffold that would mimic what the CCZ found in natural osteochondral tissue.…”

“…Understanding the transition between vascular and mineralized bone and the un-vascular and un-mineralized cartilage is crucial for the correct design of the cartilage–bone interface [ 35 , 36 ]. To date, the design and formation of a stable interface between cartilage and subchondral bone in a multi-phasic scaffold remains a significant challenge [ 33 ]. Some recent studies and review articles have showcased various efforts in interface design for osteochondral scaffolds.…”