Introduction

Extracellular matrix (ECM) derived biomaterials are commonly used in the surgical repair of different tissues and organs [1–3]. While the exact mechanism by which these bioactive scaffolds promote regeneration remains unclear, in the early stages of healing, the ECM supports the development of a pro-regenerative immune response involving both the adaptive and the innate immune system [4]. Scaffolds used clinically are typically derived from small intestine submucosa (SIS) or pericardium, and while the ECM of these tissues clearly contain structural and regulatory biomolecules generally supportive of regeneration, it is unlikely that a single tissue source of ECM will be optimal for all clinical targets. This concept is strengthened by recent studies reporting that ECM derived biomaterials can direct the differentiation of mesenchymal stem cells (MSCs) towards the phenotype of the source tissue from which they were derived [5]. This motivates the development of tissue-specific ECM derived scaffolds, potentially consisting of different layers or lineage-specific regions, especially when attempting to regenerate complex multi-phasic tissues such as the osteochondral unit of synovial joints.

Content

We have previously used the ECM from both porcine growth plate (GP) and articular cartilage (AC) to produce scaffolds for tissue engineering, with GP derived biomaterials shown to support large bone defect healing [6], and AC derived scaffolds shown to support chondrogenesis [7,8]. This talk will describe how porous scaffolds derived from these two ECMs can support the development of distinct tissue types when seeded with mesenchymal stem cells (MSCs). Next, it will be demonstrated that a bi-phasic scaffold consisting of spatially distinct but integrated layers of GP and AC ECM can be used to spatially direct MSC differentiation in vitro. It will also be demonstrated that such scaffolds support joint regeneration in vivo when implanted into critically-sized osteochondral defects in skeletally mature goats. Finally, this talk will describe how ECM derived scaffolds can be combined with 3D printed biomaterials to develop novel implants for the regeneration of focal chondral defects.

References

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Acknowledgments

Funding for this study was provided by the European Research Council Starter Grant (StemRepair – Project number: 258463), Science Foundation Ireland (SFI/12/RC/2278; 12/IA/1554) and Enterprise Ireland (CF/2014/4325)