Design of a Fibrin Microthread Composite Layer for Use in a Modular Cardiac Patch

Heart disease is currently the leading cause of death globally, and current treatments do not promote regeneration of damaged tissue. There have been significant advances in the design of scaffolds for engineered cardiac... [ view full abstract ]

Heart disease is currently the leading cause of death globally, and current treatments do not promote regeneration of damaged tissue. There have been significant advances in the design of scaffolds for engineered cardiac tissue, however, a need remains to develop an implantable myocardial patch with mechanical and functional properties that recapitulate native adult cardiac tissue to ultimately promote functional improvements of damaged myocardium. Fibrin microthreads are discrete fibrous elements with structural, mechanical and biochemical cues that mimic native fibrous tissue, that have been used as provisional scaffolds to strategically deliver stem cells to the heart and to direct skeletal muscle regeneration. In this study, we created sheets of aligned microthread-based composite scaffolds (fibrin threads in a gel) with stiffnesses that were varied by modulating the volume fraction of microthreads. Layers were created with 5, 10, or 20 microthreads resulting in layer stiffnesses ranging from ~20- 65 kPa. We also showed that we can direct cellular orientation by varying the structural cues (dependent on microthread volume fraction) and by culturing in tension (static, resulting from gel compaction). Nuclear orientation had a tighter distribution for greater microthread volume fractions of composite layers; while layers cultured in tension had tighter nuclear orientation distributions overall. We anticipate that a fibrin microthread-based composite layer will enable the design of scaffolds with tuned mechanical and anisotropically aligned structural properties to direct the orientation of cells and maximize cell-mediated contractile strain, which are ultimately vital for synchronous contractility between implanted and native tissue.