Piezoelectric pumps convert arterial mechanical energy into automatic, valve-mediated microliter dosages utilizing non-cytotoxic materials
The primary goal of this biomedical device design and implementation venture involves reducing the number of patients in developing countries that fail to complete pharmaceutical treatment schedules due to a lack of sustained access to well-equipped clinics and/or hospitals over multi-month to multi-year time spans. Another significant goal of this venture focuses on improving morbidity outcomes via implantable, sustained-release sources of essential vitamins, such as iron and folic acid.
The hydrogel-encapsulated piezoelectric micropumps will be designed using biocompatible triazole-thiomorpholine dioxide alginate hydrogel shells that evade immune detection and can be implanted with target biologics; these could include stem-cell derived beta cells, monoclonal antibodies, vaccines, or insulin.
A piezoelectric actuator in the micropump, composed of boron nitride (one possible non-cytotoxic approach), will through close adhesion/N-cadherins, communicate mechanically with pulsing arteries under physiological conditions (37 °C, 45 mmHg transmural pressure) to store an electric charge and then convert the charge into a routine valve release movement that delivers precise liquid dosages on a weekly basis. Prior research on energy harvesting utilizing arterial pulses realized values averaging 42 nanowatts and peak values of 2.38 microwatts.
Promising research efforts have demonstrated the in vivo viability of catechol-alginate-based gels that can adhere to vascular cells and withstand shear force thresholds above that of physiological blood flow, thus introducing the potential for intravascular piezoelectric devices upon demonstration of a simpler, extravascular prototype. These catechol-alginate-based vascular gels may also serve as extravascular adhesion tools by which to affix piezoelectric micropumps to vessel exteriors.
The medication dosages could enter the bloodstream through connective tissue, endothelial cell layers, or diffuse enterally for metabolic uptake.
What are the key outcomes and impact of your solution?
Key Outcome 1:
Development of low-cost scalable piezoelectric micropumps that improve morbidity statistics in developing-nation populations. This project targets those instances of death and disease that result from the challenges of long-term access to quality pharmaceutical-grade medications and/or high-dose vitamins needed for the reversal of severe deficiencies. Intermittent access to medications and intervals of access that fail to precipitate long-term patient compliance with medication instructions contribute to the instances of death and disease in question. Therefore, the provision of adequate supplies of high-quality medication at the point of care of clinics/hospitals alone would prove insufficient in contending with the long-term treatment objectives of this venture. Moreover, the provision of thorough home training programs in medication usage would also inevitably fail to adequately train every patient, as certain patients may become too ill or elderly to continue using medication with fidelity or the requisite level of precision. Implantable devices invented and engineered specifically for this drug delivery application could serve to eliminate the inefficiencies and inherent unreliability of patient-mediated daily or weekly medication usage. Implantable micropumps would also eventually eliminate the costs associated with long-term health professional home visits to administer medications and/or evaluate patient dosage compliance. Patients could visit their physicians twice yearly only upon demonstration of sustained dosage absorption and stable disease remission patterns. This would allow for a beneficial diversion of home visit resources and personnel to acute care/surgical settings.
Relevant Metric 1:
15% reduction in the number of patients that fail to take or adequately absorb a prescribed medication or necessary vitamin for one month in a selected population
Relevant Metric 2:
25% reduction in the number of patients that fail to take or adequately absorb a prescribed medication or necessary vitamin following the first six months of surgical intervention within a selected population
Relevant Metric 3:
40% reduction in the number of patients that fail to take or adequately absorb a prescribed medication or necessary vitamin following the first twelve months of surgical intervention within a selected population
Relevant Metric 4:
20 grams/liter increase in the blood hemoglobin concentration of a selected patient or patient group following the first twelve months of micropump implantation
Key Outcome 2:
Improved understanding of the microscale and nanoscale biophysics of extravascular pump-mediated drug delivery; and an improved understanding of microscale controlled drug release bioengineering
Relevant Metric 1:
Near infrared dye tracking of drug release in a selected patient or patients over one month
Relevant Metric 2:
CT/MRI imaging studies of biomaterials degradation rates in a selected patient or patient over twelve months
What actions do you propose to realize your stated goals?
Researchers and physicians involved in all stages of the prototype production and implementation process will develop a multi-year communication plan with host country officials and global health professionals local to host country clinics/hospitals.
Bioengineers and cardiophysiologists will collaborate with physicians to identify the optimal medications for microscale pump-mediated controlled drug release in developing-nation populations. These medications will likely include HIV therapeutics, vaccines, concentrated vitamin dosages, hormones, and eventually newly-developed CAR-T cancer therapeutics.
Global health practitioners will facilitate the translation of a laboratory prototype to an in-field surgical intervention amenable to weekly monitoring. Patients involved in the selected intervention will become highly literate in the precise nature of their disease and in the significance of their long-term treatment opportunities.
Patients will collect transportation and hospital stay stipends; they will also receive home visits from trained allied health professionals at least twice monthly.
Who will take these actions?
Support should commence through the guidance and efforts of university research scientists actively engaged in the fields of biomaterials, bioengineering, cardiophysiology, and/or chemical engineering. Prototype funding would ideally allow for allocation of research time and resources for at least one year. This solution's author resides in New York City with home institutions of The City College of New York Division of Science and Columbia University. Research partnerships between New York City and Boston would also be possible. MIT's Langer Lab is particularly well-suited to provide high-level mentorship for drug delivery device engineering efforts. This author refers specifically to Dr. Arturo J. Vegas of MIT and his 2016 published research on avoiding foreign body responses in implanted medical devices.
Global health organizations that currently manage developing-nation clinics and/or hospitals, such as BRAC or Partners in Health, will need to coordinate with the micropump distributor to direct the supply of the manufactured products to the most at-risk and simultaneously accessible patient populations. Funds raised for this purpose would permit long-term supply chain partnerships across a range of geographic settings. This solution's author possesses prior public health internship experience with PH-Japan of northern Thailand and prior coursework experience with Dr. Paul Farmer of Partners in Health. The referenced global health organizations employ and rely upon expert physicians and surgeons experienced in introducing U.S.-based medical technologies to rural settings. This project additionally introduces the possibility of biomaterials internships in rural hospitals to both increase the scientific literacy of and specifically train local physicians in implantable device surgery/monitoring.
The target geographies will involve central Bangladesh (through the BRAC organization), rural Rwanda (through Partners in Health), rural Thailand (through PH-Japan), rural and urban Peru (through Partners in Health), and rural Haiti (through Partners in Health).
These selections represent countries contending with major disease burdens that would benefit from long-term therapeutic interventions. The morbidities in question include HIV/AIDS, cervical cancer, breast cancer, malnutrition complications, iron deficiency, and iodine deficiency.
In Thailand alone, 440,000 people are living with HIV and 14,000 individuals died of AIDS in 2015.
In Haiti (data collected in 2011), 48 percent of pregnant women displayed blood hemoglobin concentrations under 110 g/L, which the WHO categorizes as representing a severe public health issue. One finds the same percentage for pregnant women in Bangladesh when drawing upon World Health Organization data. 43 percent of pregnant and non-pregnant women in Bangladesh had anemia as of 2011.
What do you expect are the costs associated with piloting and implementing the solution, and what is your business model?
$270,000 (university research space, researcher salaries, device materials purchases)
Research space usage for first year: $100,000
Full-time salaries for first year (three scientists): $120,000 total
Device materials purchases (raw chemicals, metals, FDA-approved biologics): $50,000
$880,000 (manufacturing costs, supply chain costs, medication costs, hospital personnel salaries/fees)
Manufacturing equipment usage: $300,000
Supply chain costs: $150,000
Medication costs: $200,000
Hospital salaries/fees/patient compensation: $230,000
This would remain a non-profit endeavor, but may inspire others in the private sector to make refinements on their own, similar microscale devices.
Funding would likely occur through collaboration with major global health NGOs with established reputations.
The parts utilized will be non-cytotoxic, bioerodable, and made out of widely-available compounds.
Any undergraduate chemistry student can produce a hydrogel with basic lab equipment. Piezoelectric pumps can be manufactured utilizing low-cost nickel and titanium supplies at the micrometer scale.
First six months:
Development of the product prototype takes place in a university biodesign lab via the efforts of mid-level or senior research scientists.
Second six months:
Prototype testing occurs using computational and physiological models across an interdisciplinary spectrum of STEM fields.
Years two through three:
Prototype undergoes further refinement and regulations approvals through results of clinical trials
Five thousand units of the micropump are manufactured and delivered to hospitals overseas. In-country surgeons implant devices during one-day patient hospital stays and global health practitioners subsequently monitor morbidity statistics over six months.
Year five and onwards:
Product manufacturing is scaled up to reach tens of thousands and eventually hundreds of thousands of at-risk patients in selected geographical regions. Proof of principle successes and refinements would likely attract progressive increases in the scale of funding every six months.
Global Vision 2020 presents similar global health treatment themes and evaluation goals.
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