2009-2010 Coulter Projects
- Broad-based diagnostic agents for amyloid diseases
- Ultrasound elastography with in-vivo compression as a pre-FNA screening tool
- In-vivo assessment of porous elastomer for pelvic organ prolapse surgery
- A cell-seeded implant scaffold for articular cartilage resurfacing
- Wireless monitoring of intraocular pressure using microelectronic technology
- Clinical feasibility of a vestibular prosthesis for Meniere's Disease
Broad-based diagnostic agents for amyloid diseases
Valerie Daggett, professor, Bioengineering
Neurodegenerative diseases, which typically target older individuals, devastate millions of patients worldwide. As the population continues to age, the diseases’ impact will significantly increase.
With the fastest growing demographic group in the developed world being people 85 and older and the high probability of acquiring a neurodegenerative disease increasing with age (>50% and increasing with age), Greg Petsko, professor of biochemistry and chemistry at Brandeis University, asserted that neurodegenerative diseases will be the ”The Next Epidemic”.
In addition to their threat to the elderly, transmissible spongiform encephalopathies present other problems: a fatal neurodegenerative disease that can be transmitted through the food supply, through tissue and organ donations, and contaminated medical instruments.
All of these modes of transmission are potentially preventable. The unmet medical need was summed up by Chicago-based science writer Janyce Hamilton: “No test. No cure. No foolproof disinfection.”
In this project a diagnostic device will be developed to detect toxic and infectious forms of amyloidogenic proteins, focusing on Alzheimer’s disease and transmissible spongiform encephalopathies. There is no cure for these diseases, so diagnostic screening of humans aims to prevent transmission of the disease through, for example, blood, organ donations, contaminated surgical instruments, medical devices (such as endoscopes) and dental equipment. Screening deer and cows would also be targeted to ensure a safe food supply.
Ultrasound elastography with in vivo compression as a pre-FNA screening tool
Yongmin Kim, professor, Bioengineering Manjiri K. Dighe, assistant professor, Radiology
Thyroid nodules are very common and most are asymptomatic, but it is clinically important to differentiate the small (~10%) malignant nodules from the benign ones. Fine needle aspiration (FNA) biopsy is currently the standard procedure for distinguishing between benign and malignant nodules. However, FNA biopsy costs in excess of $1,200 and is an invasive procedure.
The ultrasound features (i.e., echogenicity, calcification and size), used as guidelines for performing a FNA biopspy are not detailed enough to detect amalignancy. As a result, a large percentage of benign nodules undergo an FNA biopsy for diagnosis.
An unmet clinical need exists to noninvasively detect and reduce the number of FNA biopsies performed on patients with benign nodules. This would improve the use of FNA while reducing the healthcare cost associated with managing thyroid nodules.
This project will undertake two clinical studies using ultrasound (US) elastography as a pre-FNA triage tool on a large number of subjects. Based on our preliminary retrospective study, US elastography was able to decrease the number of FNA biopsies substantially by detecting nodules that are most likely to be benign. If proven effective in clinical studies, US elastography can be integrated into new and existing US machines to be used by clinicians to determine the need for an FNA biopsy when thyroid nodules are detected.
In-vivo assessment of porous elastomer for pelvic organ prolapse surgery
Buddy Ratner, professor, Bioengineering Michael Fialkow, assistant professor, Obstetrics & Gynecology
Pelvic organ prolapse (POP) is a highly prevalent condition in women characterized by abnormal bulging of the vagina into or through the vaginal canal. Over 200,000 surgeries to treat POP are performed annually in the US, and services in this area are expected to rise in the coming years by 30-45%.
Unfortunately traditional surgical treatments for POP have approximately a 30% recurrence rate and modifiable risk factors for recurrence have yet to be identified. Given the proven benefit of woven synthetic mesh implants in preventing abdominal hernia recurrence Gynecologists recently began placing similar implants within the vaginal walls during trans-vaginal POP procedures.
While accumulating evidence suggests that these materials reduce the risk of POP recurrence their utility is limited by a complication rate estimated to be 3-9% but observed as high as 24%.
The FDA released a Public Health Notification Oct. 20th 2008 about the serious complications associated with transvaginal surgical mesh use, such as erosion, fistula, dyspareunia and infection. The etiology of these complications is unknown but one hypothesis implicates the avascular foreign body response (FBR) to the materials. The FBR determines the biocompatibility of medical implants and has been found to vary according to the characteristics of the implant, such as the material surface chemistry and topography.
While biocompatibility has traditionally been defined as materials that are not harmful to living tissue, with the recognition that modification of specific material characteristics improves functional outcomes after implantation the concept of biocompatibility has evolved toward encouraging a beneficial rather than neutral or negative healing response. For example, evidence exists that implants with particular pore size and structure promote a regenerative tissue response characterized by blood vessel formation and loose as opposed to dense collagen deposition.
Using this evidence, we developed a novel technology to fabricate biomaterials with uniform pores linked by precise interpore connections (Sphere Templated Angiogenic Regeneration, STAR). In preliminary studies the STAR material promotes regenerative healing pattern characterized by normal cell types for the implant location and in particular a significantly higher proportion of vascular structures.
Accumulating data suggests that using synthetic meshes during vaginal reconstructive surgery reduces the high rate of POP recurrence, although with a high complication rate. Unfortunately, despite frequent complications the use of these materials is growing quickly. Hypothetically a more biocompatible material for the vagina would cause fewer complications. The STAR material may be a significant improvement in POP surgical implants because it should stimulate an appropriate tissue response in the vagina and it can be modified to meet the biomechanical needs for prevention of prolapse recurrence. We anticipate developing a sheet of STAR material as a product, similar to what is current then trim the sheet to size for placement in the patient.
A cell-seeded implant scaffold for Articular cartilage resurfacing
Buddy Ratner, Department of Bioengineering Paul Manner, Department of Orthopaedics & Sports Medicine
In 2004 almost 900,000 arthroplasties were performed in the United States; this will quadruple by 2026. The most common reason for this surgery is to treat arthritis. We aim to create an implant that guides the body toward biological regeneration of the damaged joint surface, using a mesenchymal stem cell seeded sphere- template poly-HEMA construct.
We have been able to fabricate large- and small-pore constructs. Further, we have succeeded in fabricating a bilayer construct, with smaller pores on the bone side, and larger pores on the cartilage side. We now have gross histologic data from animals who have undergone implantation of cell-free constructs in defects in both native and damaged cartilage.
Data points include 24 hours, 4 weeks, and 12 weeks. There is incorporation of the sphere-templated construct within cartilage, with no evidence of loss of fixation, damage to surrounding cartilage, or destruction of the implant.
Next steps include implantation of cell-seeded constructs. Many implant companies currently manufacture joint replacements; the vast majority of the United States and world market is dominated by a few, including Zimmer, DePuy/J&J, Stryker/Howmedica, Biomet, and Smith&Nephew. All involve use of metal, UHMWPE, or ceramic to reproduce the bearing surface; none provide a biologic resurfacing. Current biological products, such as Carticel, are limited to small defects (<1 cm in diameter) because they rely on expansion of articular cartilage cells. Our proposed technology involves use of stem cells placed into a bilayer substrate compose of poly-HEMA; pore sizes mimic those found in native tissue and provide a nanoscale environment for cells to differentiate down appropriate lineages and recreate native tissue.
Wireless Monitoring of Intraocular pressure using microelectronic technology
Buddy Ratner, professor, Bioengineering Tueng T. Shen, assistant professor, Ophthalmology
Clinical feasibility of a vestibular prosthesis for Meniere's Disease
Jay Rubenstein, professor, Bioengineering James Phillips, research associate professor, Otolaryngology-HNS
Vestibular dysfunction affects a large and growing population and poses a major public health problem due to disability and lost productivity. It is caused by a diverse group of disorders that may manifest as attacks of vertigo or chronic disequilibrium, either of which may secondarily lead to catastrophic falls, particularly for the elderly.
Current therapy for vestibular disfunction, while helpful, is suboptimal. It consists primarily of ablative therapies for disorders, such as Meniere’s disease, characterized by paroxysmal attacks of vertigo, and physical therapy, termed vestibular rehabilitation, for those disorders producing chronic imbalance. The latter symptom is typically produced by unilateral or bilateral vestibular loss. Bilateral disease, in particular, condemns those affected to a lifetime of postural instability and oscillopsia, or inability to maintain steady gaze while in motion.
The tremendous success of the cochlear implant in treating deafness has led neurotologists, vestibular scientists, the medical device industry and the NIDCD to question whether a vestibular implant might be an effective treatment for a variety of vestibular disorders. Such a device would electrically stimulate the diseased vestibular labyrinth to provide missing afferent signals in the manner comparable to how a cochlear implant stimulates the cochlea. The investigative team has previously received funding from NIDCD to develop and study a vestibular implant in the non-human primate. A device, suitable for human use, has already been designed in collaboration with the Cochlear Corporation, fabricated and implanted in the rhesus monkey.
These studies give us the necessary physiologic information to proceed with similar studies in human subjects. Meniere’s disease is the target condition for these studies because it is a common debilitating condition frequently treated surgically when medical management fails. In addition, it is likely that effective treatment of Meniere’s disease will not require a velocity sensor to modulate the prosthesis.
By using patients with Meniere’s disease as the pilot subjects, much can be learned about clinical implementation of a vestibular prosthesis that may facilitate possible treatments of other vestibulopathies, including those that require a velocity sensor to be effective. However, due to the high incidence of disability caused by Meniere’s symptoms, Meniere’s disease alone represents an important clinical problem and a highly attractive market for a neurostimulation company.
