NSF Award
2320185
Non-technical Abstract:<br/>Fibers are a highly versatile geometry that can be fabricated into a range of implant geometries (meshes, tubes, ropes) using manufacturing methods developed and routinely used by the textile industry. Unfortunately, synthetic fibers are recognized by the human body as a foreign material which makes them challenging to use as medical implants. As an alternative to synthetic fibers, the overall research goal of this project is to develop a fiber built using the molecules, like collagen, that are secreted by living cells. These all-natural biofibers would avoid the foreign material response directed by the body against synthetic polymeric materials, but could still be used with currently available textile fabrication techniques in order to make various medical products. More broadly, the proposed research could help establish a supply of materials that would help alleviate the shortage of donated human tissues and address the complications associated with medical implants that use synthetic fibers. To create these biofibers, the investigators will develop innovative methods to farm the molecules that are secreted by populations of cells during growth in the lab. Specifically, the investigators will create a toolbox of cell derived biofibers using key human cells and then explore methods to fabricate these human cell derived biofibers into beneficial medical implants. To enhance the broader impact of this study the research will be complemented by educational projects at the undergraduate and K-12 academic levels. Highlights include the creation of a rural biomedical engineering middle school summer program, the integration of fiber projects into the university courses, and the involvement of undergraduate students through participation in existing University programs.<br/><br/>Technical Abstract: <br/>The investigators will develop biomaterial fibers that are built from the extracellular matrix (ECM) molecules secreted by cells. To do so the team will explore methods to farm the ECM that is secreted by populations of cells during growth in culture. While methods to collect isolated molecules from cells have existed for some time, the wholesale collection of cell secreted ECM proteins to create bulk biomaterials is unique. The overall goal is to fabricate woven biomedical implants using ECM as an alternative to synthetic polymer fibers. To collect the ECM that cells secrete, the investigators will utilize a solvent degradable hollow fiber membrane (HFM). When cells are seeded into the HFM and grown in culture they secrete a multitude of ECM molecules that accumulate within the lumen. The innovative step is that the HFM can be thoroughly dissolved using a water miscible solvent, stripping away the synthetic component, and leaving behind the accumulated ECM fiber. The result is a biofiber formed entirely from the ECM secreted by cells. The proposed research program will investigate the synthesis of next generation human ECM biofibers using clinically relevant cell types (cardiac, muscle, vascular); optimize synthesis methods and model the influence of pro-collagen synthesis schemes on ECM biofiber properties and identify combinations that optimize yield and mechanics; genetically engineer producer cells with specialized ECM production capabilities and examine the properties of ECM biofibers synthesized using them; characterize the in-vivo host response to implanted ECM biofibers, with particular attention given to inflammation and fibrotic tissue formation; and lastly create scaled-up biofiber manufacturing schemes and utilize textile production schemes to create woven biofiber constructs. To enhance the broader impact of this study the research will be complemented by integrated educational projects at the undergraduate and K-12 academic levels, both within the University of Arkansas and as educational outreach.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
