Developing quality analysis and process control methods for the production of collagen-based implants for wound healing
The goal of this work is to develop methods for collagen isolation and processing to facilitate manufacturing of implants to accelerate wound healing. Because collagen is isolated from tissues, there is a great deal of variability in preparations that affects implant performance. Further, the shelf life of these raw materials is often short, and the effects of storage on implant performance is not well understood. This project will determine the effect of collagen purity and storage time on structure and properties of collagen-based implants. A key feature of the process of making implants is forming patterned collagen gels to promote implant vascularization. As such, controlling the phase transitions of collagen gels, their microstructure, and mechanical properties is critical to making functional implants. We will use rheology and electron microscopy facilities in CCMR to monitor phase transitions, properties, and microstructure of collagen gels as a function of collagen purity and storage time. We are partnering with Fesarius Therapeutics, a New York State startup biotechnology company, which is commercializing implants for wound healing technology invented at Cornell University. This work will provide key information to Fesarius regarding the mechanical performance and shelf life of such implants.
Industry Partner: Fesarius Therapeutics
Academic PI: Lawrence Bonassar, Biomedical Engineering & Mechanical and Aerospace Engineering
Choline and docosahexaenoic acid: A synergistic approach to improve DHA delivery to fetal tissue
Our proposed experiments seek to characterize the synergy between dietary choline and the omega-3 fatty acid DHA throughout pregnancy. Substantial evidence over the past few decades has clearly shown a distinct need for DHA during pregnancy and lactation, while new findings have highlighted the importance of adequate choline nutriture during these critical time periods. Research that investigates the synergy between these two nutrients has substantial implications for dietary recommendations and prenatal supplementation formulations as a means of improving pregnancy outcomes. Intake needs for the essential nutrient choline, a principal constituent of the cellular membrane phospholipid phosphatidylcholine (PC), are acutely high during pregnancy, a time when cellular proliferation and tissue expansion are accelerated. The goal of the present study is to determine the impact of maternal choline supplementation during pregnancy on the dynamics of maternal-fetal DHA transfer. Outcomes of this study are expected to provide rationale for a re-evaluation of choline recommendations during pregnancy as well as to guide the development of prenatal supplement formulations/products that support optimal fetal brain development and future neurological health.
Industry partner: Balchem Corp.
Academic PI: Marie Caudill, Division of Nutritional Sciences
Electric cell-substrate impedance sensing (ECIS)-based cell anomaly detector
We are proposing an impedance-based approach to provide laboratories growing animal cells with a test that can provide assurance that cultures being used are not misidentified or contaminated with mycoplasma. The proposed technology is not a replacement for the essential molecular and biochemical techniques that definitively define a cell population or test directly for mycoplasma. Rather we propose the development of a cell assurance monitor (CAM) that would provide researchers with reasonable confidence that a culture is of known identity and uncontaminated. To be practical, such a test must be affordable and simple to administer such that it can be applied frequently – even on a weekly basis. To be effective, this technology must also provide a simple quantitative summary that varies significantly with cell type and with contamination after controlling for common sources of experimental variation including cell inoculation density, passage number, and time since last medium change. In the proposed collaboration, data generation for multiple established cell lines will be managed by our company partner, Applied BioPhysics, Inc., and the statistical analysis of the data will be led by Prof. Matteson with the aid of a Cornell University graduate student research assistant.
Industry partner: Applied BioPhysics, Inc.
Academic PI: David Matteson, Department of Statistical Science
Developing a choline technology to mitigate fatty liver disease in dairy cattle
Our overall goal is to develop nutritional approaches to prevent fatty liver disease in dairy cattle. This proposal will determine whether choline promotes the secretion of lipoprotein triglyceride from bovine liver tissue and cells. We will also identify potential promoters and inhibitors of choline efficacy. Dairy cows develop fatty liver disease (FLD; i.e. steatosis) during the transition from gestation to lactation. Established FLD increases a cow’s risk of developing a related metabolic disease (e.g. ketosis), and compromises their milk production, fertility, and longevity. Although the mechanisms of FLD are not completely defined, limited hepatic phosphatidylcholine (PC) synthesis is believed to be involved. Our goal is to identify nutritional approaches to increase hepatic PC synthesis and promote liver lipid disposal to alleviate FLD. Because the Balchem is the global leader in choline supplementation, a partnership with Balchem to identify a nutritional therapy that improves liver health in dairy cows is logical. Furthermore, the revision of the National Research Council Nutrient Requirements for Dairy Cattle to include choline as an essential nutrient for dairy cows has the potential transform dairy nutrition practices and improve cow health which will favor a greater New York workforce and sales for the Balchem.
Academic PI: Joseph McFadden, Department of Animal Science
Amphiphilic polymer conjugates for the treatment of dry eye disease
The scientific goal of the proposed research is to develop and ultimately commercialize a new eye drop formulation that stabilizes the tear film for the treatment of dry eye disease. Dry eye disease is caused by an unstable tear film that breaks and exposes the cornea directly to air. Current treatments require frequent administration of viscous eye drops (the effect last only for a few minutes) or are effective in a small cohort of patients (immunosuppressants). The proposed eye drop formulation is comprised of amphiphilic polymer conjugates that maintain the integrity of the tear film. We have teamed with Bausch & Lomb to develop a series of amphiphilic polymers and to move toward the commercial goal of improving tear film stability and reduce pain and discomfort in dry eye patients. The commercial goal is to generate composition-of-matter and methods-of-use intellectual property to either license to our Rochester, NY-based industrial partner or to develop as a new commercial enterprise to be located in Ithaca, NY.
Industry partner: Bausch & Lomb
Academic PI: David Putnam, Biomedical Engineering, Chemical and Biomolecular Engineering
Extended efficacy of biomimetic boundary lubricants in the rat ACLT model of osteoarthritis
Cornell University’s biomimetic boundary lubricants (BBL) lubricate and protect joint tissue. Cornell’s BBL’s are closely related to medical polymers currently in wide use and which are generally regarded as safe (GRAS). They are being developed to provide a bridge between medical treatment for severe osteoarthritis (OA) of the knee and joint replacement surgery. Currently, the standard of care for these patients is injections of hyaluronic acid (HA) compounds for viscosupplementation in the affected joint spaces. By lubricating the joint tissues, HA compounds can alleviate pain. However, these HA affects are transient and short-lived. In contrast, injections of Cornell’s BBL have prevented disease progression and preserved joint health in standard rat models of injury induced OA. BBL performance in these models relative to the historical performance of HA compounds in similar OA models suggest the potential for Cornell’s BBLs to eventually eclipse HAs in this market segment. Further demonstration of BBL animal and—eventually—human safety and efficacy will be required to determine whether they can fulfill their promise for this indication. This collaboration with Dynamic Boundaries provides the opportunity to add significant value to Cornell’s BBL technology by demonstrating extended efficacy in an in vivomodel of OA.
Industry partner: Dynamic Boundaries
Academic PI: Heidi Reesink, College of Veterinary Medicine
Development of high-throughput metabolic profiling platform for active ingredients in toxicity screening industries for improved product safety
The partnership between the Schroeder group at Cornell University and Zymtronix is to develop a new metabolic screening platform geared to the pharmaceutical, consumer care product and chemical industries that produces physiologically relevant metabolites of active chemicals rapidly and cost-efficiently for toxicological analysis. This allows clients to produce and identify metabolites with high sensitivity and assess their safety for FDA approval, and to ensure costumer safety. The CAT collaboration will support the development and validation of our new technology as a key step towards commercialization in the drug metabolism and pharmacokinetics industries involved in preclinical drug development.
Industry Partner: Zymtronix
Academic PI: Frank Schroeder, Chemistry and Chemical Biology
Topical therapeutics for skin diseases associated with DNA damage
UV exposure to the skin has one of the most damaging effects on the genomic integrity of a cell. Constant UV exposure induces DNA damage and accumulation of the damages leads to premature cell death or the incorporation of mutations leading to consequential changes to cellular function. While cells have the ability to correct this damage through a process called the nucleotide excision repair (NER) pathway, our data suggests that this process is working at less than its full potential and that pharmacological intervention may indeed enhance the cells' ability to repair the damage. We have previously identified chemical compounds that can enhance that NER pathway. The goal of this project is to identify novel active ingredients and analogs for compounds found in our previous studies that are capable of enhancing the natural DNA repair mechanism in cells more efficiently. This technology can then be used for a wide variety of applications ranging from cosmetics (antiaging, skin enhancement topical application) to therapeutics (skin care prescription creams for DNA damage related diseases).
Industry partner: Repairogen
Academic PI: Pengbo Zhou, Weill Cornell Medical College