Cell-synthesized Thread-based Tissue Engineering

DESCRIPTION (provided by applicant): Previously, we have reported excellent clinical results with a tissue engineered vascular graft built using a self-assembly approach termed Sheet-Based Tissue Engineering (SBTE). The principal drawback of this approach, however, is the high manufacturing costs due to a long production time. In order to make this technology clinically available, we need to find a more commercially viable manufacturing approach. We hypothesized that we could build cell-synthesized threads that could be assembled into more complex constructs. This novel evolution of our technology builds upon the clinical successes demonstrated for SBTE (long-term strength and durability, remarkable biocompatibility, resistance to infection, and anti-thrombogenicity) but now introduces the possibility of a faster and less costly assembly strategy using existing medical textiles technologies. The overarching objective of this grant is to develop the foundation for this novel self-assembly platform technology, which we term Thread-Based Tissue Engineering (TBTE). In preliminary studies we have demonstrated that we can produce cell-synthesized threads and weave or braid tubular conduits. Importantly, this reduces the manufacturing time of the vascular graft from over 7 months to less than 3 months. While our first target is to produce a small diameter blood vessel for vascular reconstruction, TBTE will be a very versatile platform technology that can provide a scaffold for a variety of target tissues and organs. In order to develop the basic tools and initial prototypes for the in vivo studies planned for Phase II, this Phase I project will achieve the following specific aims: 1. Generate a library of human threads and determine their Mechanical properties. 2. Generate a library of canine threads and determine their mechanical properties. 3. Build prototype blood vessels and mechanical milestones. DELIVERABLE AND GO/NO GO MILESTONE: In this proof-of-concept study, we will need to demonstrate an assembly protocol that produces blood vessels that meet the critical mechanical properties release criteria we have established for our previous clinical trials with the sheet-based tissue engineered vascular grafts (burst pressures gt1700 mmHg and suture pull-out strength gt 75 gf). PUBLIC HEALTH RELEVANCE: Over the last 10 years we have developed a completely biological tissue engineered vascular graft comprised exclusively of human cells, without the need for exogenous biomaterials or synthetic scaffolds. While initial clinical use of this engineered graft represented a landmark achievement in the field, the manufacturing process is time consuming and expensive and thus, we are exploring a new manufacturing process, termed thread based tissue engineering (TBTE), in which cell-synthesized, biological threads can be woven or braided into robust tissues, decreasing the total manufacturing time down from 6-9 months in previous studies to 3-8 weeks. In this grant, we plan to build and characterize a library of threads built from human and animal cells and this library of functional and mechanical characteristics will form the basis for manufacturing more complex tissues, including a vascular graft for in vivo use in Phase II of this SBIR funding mechanism.