More than 16 million Americans have been diagnosed with Dry Eye Disease (DED). This number is growing due to aggravating factors like increased screen time, and an aging population. It already has an estimated impact of $6.58 billion on the US healthcare system and $70 billion overall economic impact due to decrease in productivity. Two contributing factors to this burden are the price an inadequacy of existing treatments. Common treatments include pharmaceutical drops, lubricant drops, and punctal plugs. Collectively, these therapies are plagued by poor compliance, poor efficacy, discomfort, and untenable costs. Pharmaceutical drops (i.e. Cyclosporine) can also take months to achieve an effect. Punctal plugs offer rapid symptom relief but are prone to sizing issues, patient discomfort, and in some cases the need for surgical removal. They are made in approximately the same designs and with the same materials as at their invention over forty years ago. Our objective is to develop a patient-adaptable punctal plug using environmentally sensitive hydrogels which exhibit a reverse phase transition. An abundance of literature, including prior academic research by members of our team, illustrates the desirable properties of N- isopropylacrylamide copolymers for biomedical applications. The majority of these applications are aimed at drug release, and to-date no one has designed a material suitable for a long-term medical insert. Durability, reliable long-term transition behavior, and scalable manufacture and processing are all functional barriers to development. The AesculaTech team developed an early model of such a material and a prototype applicator which can store it for two months. When inserted, the plug flows into the duct as a liquid, molding to patient anatomy before solidifying. Upon a standard irrigation procedure, this material reverts back to flowable gel for removal. Short term early data has also shown preliminary biocompatibility. As a new medical material, this plug requires optimized and reliable behavior for commercially competitive long-term use. If this project is successful, it will provide a wealth of information on new responsive hydrogels and produce a plug which improves outcomes and provides a safer and easier alternative for most patients. Phase 1 will research new smart hydrogels, using rheology and simulated use to identify a commercially suitable material. The Applicator will also be optimized for usable shelf-life. Phase 2-1 will rigorously test the chemical and biological safety of the device using extract-based and direct contact methods along with generating a list of contraindicated products. Phase 2-2 will clinically validate the performance of the product.
Public Health Relevance Statement: Project Narrative This project will yield a comprehensive characterization of novel patient-adaptable materials and a means of reliably delivering them for ophthalmic applications. By engineering molecules and formulations for smart hydrogels and establishing their safety and efficacy for use as a punctal plug to treat Dry Eye Disease, this project fits objective 1 of the NEI's Strategic Plan - drive innovative research. This multi-disciplinary biomedical engineering project has the potential to not just improve treatment for Corneal disease, but also unlock a new class of medical materials for personalized biomedical devices and combination products.
Project Terms: Adhesions; Adoption; Aging; Anatomic Sites; Anatomic structures; Anatomy; Back; Dorsum; Behavior; Biocompatible Materials; Biomaterials; biological material; Biomedical Engineering; bio-engineered; bio-engineers; bioengineering; biological engineering; Clinical Research; Clinical Study; Corneal Diseases; Corneal Disorder; cornea disorder; Cyclosporine; Ciclosporin; CsA; Cyclosporin A; Cyclosporine A; Sandimmun; SangCya; neoral; sandimmune; Diagnosis; Disincentive; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Dry Eye Syndromes; Dry eye disease; Keratoconjunctivitis Sicca; Dwarfism; Nanism; dwarf; Economics; economic; Engineering; Environment; Exhibits; Family; Foreign Bodies; Gel; Healthcare Systems; Health Care Systems; Human; Modern Man; In Vitro; Irrigation; Lavage; Nonvaginal irrigation; Nonvaginal lavage; irrigation therapy; lavage therapy; other than vaginal Douching; other than vaginal Irrigation; Literature; Marketing; Methods; Molecular Structure; Macromolecular Structure; Patients; Polymers; polymer; polymeric; Productivity; Recommendation; Research; Rheology; Safety; Structure-Activity Relationship; chemical structure function; structure function relationship; Temperature; Testing; Thinness; Leanness; Time; Toxicology; Price; pricing; N-isopropylacrylamide; Device Safety; Risk Assessment; crosslink; improved; Procedures; Application procedure; Site; Solid; Clinical; Phase; biologic; Biological; Medical; Chemicals; Recovery; Lubricants; fluid; liquid; Liquid substance; eye dryness; dry eye; Molds; Filamentous Fungi; Life; Mechanics; mechanic; mechanical; Clinic; Protocols documentation; Protocol; American; biomaterial compatibility; biocompatibility; copolymer; experience; monomer; Performance; Hydrogels; Toxic effect; Toxicities; novel; member; economic impact; Duct (organ) structure; Duct; Modality; Devices; Excision; Abscission; Extirpation; Removal; Surgical Removal; resection; Positioning Attribute; Position; Radiation; Modeling; Property; response; Adverse event; Adverse Experience; veterinary science; Drops; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; pharmaceutical; Pharmacologic Substance; Phase Transition; Symptoms; Data; Economic Burden; Strategic Planning; in vivo; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; patient oriented outcomes; Development; developmental; nanocomposite; nano composite; screen time; television watching; tv watching; cost; burden of disease; disease burden; years of life lost to disability; years of life lost to disease; burden of illness; designing; design; Outcome; innovate; innovative; innovation; resistant; Resistance; multidisciplinary; usability; prototype; commercialization; aged population; population aging; aging population; common treatment; bodily sensation; Medical emergency; invention; Formulation; improved outcome; systemic toxicity; alleviate symptom; ameliorating symptom; decrease symptom; fewer symptoms; relieves symptoms; symptom alleviation; symptom reduction; symptom relief; reduce symptoms; Injections; financial burden; financial distress; financial strain; financial stress; Financial Hardship; COVID crisis; COVID epidemic; COVID pandemic; COVID-19 crisis; COVID-19 epidemic; COVID-19 global health crisis; COVID-19 global pandemic; COVID-19 health crisis; COVID-19 public health crisis; COVID19 crisis; COVID19 epidemic; COVID19 global health crisis; COVID19 global pandemic; COVID19 health crisis; COVID19 pandemic; COVID19 public health crisis; SARS-CoV-2 epidemic; SARS-CoV-2 global health crisis; SARS-CoV-2 global pandemic; SARS-CoV-2 pandemic; SARS-CoV2 epidemic; SARS-CoV2 pandemic; SARS-coronavirus-2 epidemic; SARS-coronavirus-2 pandemic; Severe Acute Respiratory Syndrome CoV 2 epidemic; Severe Acute Respiratory Syndrome CoV 2 pandemic; Severe acute respiratory syndrome coronavirus 2 epidemic; Severe acute respiratory syndrome coronavirus 2 pandemic; corona virus disease 2019 epidemic; corona virus disease 2019 pandemic; coronavirus disease 2019 crisis; coronavirus disease 2019 epidemic; coronavirus disease 2019 global health crisis; coronavirus disease 2019 global pandemic; coronavirus disease 2019 health crisis; coronavirus disease 2019 pandemic; coronavirus disease 2019 public health crisis; coronavirus disease crisis; coronavirus disease epidemic; coronavirus disease pandemic; coronavirus disease-19 global pandemic; coronavirus disease-19 pandemic; severe acute respiratory syndrome coronavirus 2 global health crisis; severe acute respiratory syndrome coronavirus 2 global pandemic; COVID-19 pandemic; sealant; manufacture
