Regenerative Engineering: Studies of the Rotator Cuff and other Musculoskeletal Soft Tissues

Abstract

ABSTRACT‘Regenerative Engineering’ is the integration of advanced materials science, stem cell science, physics, developmental biology and clinical translation to regenerate complex tissues and organ systems. Advanced biomaterial and stem cell science converge as mechanisms to guide regeneration and the development of prescribed cell lineages from undifferentiated stem cell populations. Studies in somite development and tissue specification have provided significant insight into pathways of biological regulation responsible for tissue determination, especially morphogen gradients, and paracrine and contact-dependent signaling. The understanding of developmental biology mechanisms are shifting the biomaterial design paradigm by the incorporation of molecules into scaffold design and biomaterial development that are specifically targeted to promote the regeneration of soft tissues. Our understanding allows the selective control of cell sensitivity, and a temporal and spatial arrangement to modulate the wound healing mechanism, and the development of cell phenotype leading to the patterning of distinct and multi-scale tissue systems.Building on the development of mechanically compliant novel biomaterials, the integration of spatiotemporal control of biological, chemical and mechanical cues helps to modulate the stem cell niche and direct the differentiation of stem cell lineages. We have developed advanced biomaterials and biomimetic scaffold designs that can recapitulate the native tissue structure and mechanical compliance of soft musculoskeletal tissues, such as woven scaffold systems for ACL regeneration, non-woven scaffolds for rotator cuff tendon augmentation, and porous elastomers for regeneration of muscle tissue. Studies have clearly demonstrated the modulation of stem cell response to bulk biomaterial properties, such as toughness and elasticity, and scaffold structure, such as nanoscale and microscale dimensions. The integration of biological cues inspired from our understanding of developmental biology, along with chemical, mechanical and electrical stimulation drives our development of novel biomaterials aimed at specifying the stem cell lineage within 3-dimensional (3D) tissue systems. This talk will cover the development of biological cues, advanced biomaterials, and scaffold designs for the regeneration of complex soft musculoskeletal tissue systems such as ligament, tendon, and muscle.