Modified carrageenan-based nanomaterials as sustainable, immunomodulatory, hemocompatible, and antibactieral biomaterials

Medical implants, including stents used to open diseased arteries, orthopedic implants that restore the use of limbs and joints, implanted blood glucose sensors that help manage diabetes, and many other devices, are primarily composed of synthetic polymers and metals. Negative biological responses often occur when these materials are introduced into the body.

Many implants fail due to unfavorable blood-material interactions, inflammation, and infection. Blood clotting on cardiovascular implants can lead to heart attacks and strokes. Chronic inflammation around implants can cause non-healing wounds and degrade sensor performance.

Bacterial infection on implant surfaces can be exceedingly difficult to treat. Patients can be treated with drugs to reduce these risks (such as anticoagulants, anti-inflammatories, and antibiotics), but these may have long-term side effects. Instead of treating patients with drugs, blood reactions, inflammation, and infection should be addressed by developing new materials that have more favorable interactions in the biological environment.

This research is inspired by biology to develop new materials for biomedical implants. Living organisms, including animals, plants, fungi, algae, and bacteria all produce sugar-based, natural polymers called polysaccharides. Some polysaccharides provide structural support for tissues, while other polysaccharides govern important biochemical processes or exhibit antibacterial and antifungal activity, protecting tissues from harmful infections.

These polysaccharides are organized at the nanoscale in living tissues. Algae produce a class of polysaccharides called carrageenans that are used commercially in food, cosmetics, and health care products. This research project will develop modified carrageenans with chemical and nanoscale features specifically designed to reduce inflammation, modulate blood clotting, and enhance antimicrobial activity.

The use of carrageenans, as opposed to synthetic polymers or polysaccharides from animal tissues, will provide a sustainable source for implant materials with inherent anti-inflammatory and antimicrobial activity, improving outcomes for patients. The research will be conducted in collaboration with experts from Latin America and is integrated into outreach activities to youth and the general public in underprivileged communities.

Heparin is harvested from animal tissues and used clinically as an anticoagulant. Heparin and other sulfated glycosaminoglycans, such as chondroitin sulfate, have generated significant interest in tissue engineering for their ability to stabilize growth factors and potentiate other biochemical functions. Synthetically sulfated/sulfonated polymers (e.g., polystyrene sulfonate, dextran sulfate) have also been proposed as new biomaterials; however, they require the use of harsh and toxic sulfation chemistries.

Carrageenans are naturally sulfated polysaccharides, commercially produced for food, cosmetic, and pharmaceutical uses. They are potential alternatives to mammalian glycosaminoglycans. However, their chemical modification and processing into nanomaterials for biomedical applications is unexplored in the existing literature.

This research will produce a library of chemically modified carrageenans to (i) enable their assembly into nanostructured materials surfaces, (ii) modulate protein binding and cellular inflammation on surfaces, (iii) enhance blood compatibility, and (iv) introduce antibacterial activity. The research is designed to elucidate structure-property-function relationships of this important class of renewable nano-biomaterials that will be developed to have immune-instructive properties.

The work involves PhD students from a collaborator’s laboratory in Latin America and will include outreach with new programming to engage underserved communities at a public-facing campus recently opened in the Denver metropolitan area.

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.