Biofabrication of soft tissue templates for engineering the bone–ligament interface

5 years ago

Biofabrication of soft tissue templates for engineering the bone–ligament interface

Simon Carroll, Kevin Mulhall, David Morrissey, Ella Harris, Daniel J. Kelly, Yurong Liu, Grainne Cunniffe

Regenerating damaged tissue interfaces remains a significant clinical challenge, requiring recapitulation of the structure, composition, and function of the native enthesis. In the ligament-to-bone interface, this region transitions from ligament to fibrocartilage, to calcified cartilage and then to bone. This gradation in tissue types facilitates the transfer of load between soft and hard structures while minimizing stress concentrations at the interface. Previous attempts to engineer the ligament–bone interface have utilized various scaffold materials with an array of various cell types and/or biological cues. The primary goal of this study was to engineer a multiphased construct mimicking the ligament–bone interface by driving differentiation of a single population of mesenchymal stem cells (MSCs), seeded within blended fibrin-alginate hydrogels, down an endochondral, fibrocartilaginous, or ligamentous pathway through spatial presentation of growth factors along the length of the construct within a custom-developed, dual-chamber culture system. MSCs within these engineered constructs demonstrated spatially distinct regions of differentiation, adopting either a cartilaginous or ligamentous phenotype depending on their local environment. Furthermore, there was also evidence of spatially defined progression toward an endochondral phenotype when chondrogenically primed MSCs within this construct were additionally exposed to hypertrophic cues. The study demonstrates the feasibility of engineering spatially complex soft tissues within a single MSC laden hydrogel through the defined presentation of biochemical cues. This novel approach represents a new strategy for engineering the ligament–bone interface. Biotechnol. Bioeng. 2017;9999: 1–12. © 2017 Wiley Periodicals, Inc. A novel strategy for the biofabrication of a multiphased tissue mimicking the ligament-bone interface is presented. Seeded in both stratified and homogenous blended hydrogels composed of fibrin and alginate, mesenchymal stem cells were driven down a chondrogenic, fibrocartilaginous or ligamentous pathway through spatial presentation of growth factors along the length of the construct within a custom-made culture chamber. Spatially distinct regions of cellular differentiation and matrix deposition matching a cartilaginous and ligamentous phenotype were demonstrated.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/bit.26362