Functional Glycopolymer Tissue Engineering Scaffolds from a Natural Glycolipid with Chondrogenic and Anti-inflammatory Properties

Rensselaer Polytechnic Institute, Troy NY

Investigators

Abstract

Non-technical: This award to Rensselaer Polytechnic Institute is to develop an effective strategy to repair cartilage defects associated with osteoarthritis while also treating chronic inflammation which often propagates joint deterioration. Current clinical treatments for cartilage defects can temporarily restore joint function. However, these methods fail to treat the chronic inflammatory cycle that contributes to tissue degeneration associated with osteoarthritis. A tissue engineering scaffold will be developed that not only restores the function of locally damaged cartilage but also provides for the sustained release of anti-inflammatory molecules into the surrounding lubricating synovial fluid as the scaffold degrades. Toward this goal, the PI will further develop a unique family of biomaterials derived from a natural building block produced by yeast cells that consists of fatty acid and sugar residues. The polymers, prepared by a "green chemistry" approach, will be tuned so that they have the required biological properties needed for the tissue engineering scaffold. Furthermore, after the biomaterial performs its function, it will hydrolytically degrade to safe molecules. Ph.D., undergraduate and high school students participating in this program will gain critically important skills in modern organic and polymer synthesis, biocatalysis, cell-biology methods and in the fabrication of biomaterials into desired forms. Students will work in teams, learn critical communication skills and will develop a deep appreciation for interdisciplinary research problems. Technical: The proposed research seeks to develop a tissue engineering strategy to repair cartilage defects associated with osteoarthritis while also treating chronic inflammation which often propagates joint deterioration. Objectives in the proposed studies are to: 1) develop a library of glycopolymers synthesized by the ring-opening metathesis polymerization (ROMP) of a yeast produced lactonic glycolipid that is decorated with a range of specific chemical moieties that are known to be chondrogenic and/or anti-inflammatory, 2) generate and characterize porous glycopolymer biomaterial scaffolds and 3) evaluate through in vitro investigations the chondrogenic and anti-inflammatory properties of these scaffolds to identify scaffolds warranting future in vivo evaluation. A key strategy in this work is the use of lactonic sophorolipids (LSLs) as building blocks since they are easily produced by fermentations in high yields (>300 g/L). Furthermore, LSLs are amenable to a wide range of selective modification reactions both prior to or after polymerization that provides a platform for bioresorbable biomaterials whose structure and, therefore, functional properties, can be "tuned" as required. High school, undergraduate and Ph.D. students will be organized into teams in order to: i) provide mentoring opportunities between students at different levels and ii) to simulate today's workplace that increasingly utilizes interdisciplinary teams to solve complex problems. In this way, students in the program will gain an understanding and appreciation of high-level teamwork and communication between disciplines.