Month: September 2020

So far, the team has been discussing and finalizing requirements. Since this project consists of two main devices, an implantable valve and a catheter delivery mechanism, requirements were broken down as such and are as follows:

Valve Requirements

Requirement	Specification	Justification
1.) The device must remain intact while it is serving its purpose in the patient’s body.	1.1) Must be able to support a large range of pH present in urine (pH 5-8)  [5].	1.1) pH changes can damage a material
	1.2) Last at least 5 years [8]	1.2) In children, VUR often fixed within 5 years [8]
2.)  The device must support normal urine flow into the bladder	2.1) The device must be able to support flow rates up to 25 mL/hour	2.1a) Flow rate is between 17.5-23.6 mL/hour [12]
		2.1b) Urine flow is pulsatile/dynamic flow, not just steady state [12].
	2.2) The device must be able to support intra-abdominal pressure up to 20 mmHg	2.2) Intra-abdominal pressure  up to 5 mmHg is normal in adults, but with conditions such as obesity, it can get as high as 15 mmHg. Above 20 mmHg is associated with organ dysfunction [14].
3.) The device must “grow” with a child if a long-term fixture	3.1) The material needs to be able to elastically strain 233%  to change with the ureter.	3.1) The ureter starts at 3-5 mm in healthy kids, greater than 7 mm in kids with VUR [15]
4.) The device must be biocompatible		4.) For any medical device approved by the FDA, biocompatibility testing must be doe following ISO 10993-1 [1].
5.) The device must stay in place		5.) Movement of the valve will initiate an immune response [4]

Catheter Requirements

Requirement	Specification	Justification
1.) The device must be able to reach the vesicoureteral junction.	1.1) The placement device must be able to range in length from 2 cm to 30 cm to accommodate both males and females, children and adults.	1.1a) The adult male urethra ranges from 15-30 cm long [2].
	1.1b) The average female child’s urethra length is 2.59 cm [3]
2.)The device must be able to fit into the urethra.	2.1) The catheter tubing must be less than 3 mm in diameter.	2.1) In children, the average diameter of the urethra is 3-4 mm [9].
3.1) The device must be able to place the valve correctly, and then be separated from the valve for removal from the body.	3.1) Once placed, the valve does not move more than 2 mm once separated from the catheter.	3.1a) This is the function of the device, as a catheter long-term would be uncomfortable for a child.
	3.1b) If the valve moves during placement, it needs to be close enough to still support the natural flap.
4.) The device must be biocompatible.		4.) For any medical device approved by the FDA, biocompatibility testing must be doe following ISO 10993-1 [1].

Additional Requirements

Requirement	Justification
1.) The delivery of the devices must be simple and does not require additional surgical training.	1.) The goal of the company is to make the device usable internationally, especially in areas with fewer medical professionals.
2.) The cost of the procedure must be equivalent of already existing treatments	2.) The goal of the company is to ensure that insurance companies cover most of the cost.
3.) The devices must be manufactured at TCNJ	3.) Rules of senior project
4.) The devices must be as environmentally friendly as possible	4.) The goal of the company is to ensure a low carbon footprint, which can be done through the use of recycled materials in packaging

 

References

[1] FDA, Special Considerations – Biocompatibility. 05/22/2020. https://www.fda.gov/medical-devices/premarket-notification-510k/special-considerations#bio

[2]Kohler, Tobias S et al. “The length of the male urethra.” International braz j urol : official journal of the Brazilian Society of Urology vol. 34,4 (2008): 451-4; discussion 455-6. doi:10.1590/s1677-55382008000400007

[3]Halleran, Devin R., et al. “Urethral Length in Female Infants and Its Relevance in the Repair of Cloaca.” Journal of Pediatric Surgery, vol. 54, no. 2, 2019, pp. 303–306., doi:10.1016/j.jpedsurg.2018.10.094.

[4] “Recommendations.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 5 Nov. 2015, www.cdc.gov/infectioncontrol/guidelines/cauti/recommendations.html.

[5] Feher, Joseph. Quantitative Human Physiology. Elsevier. 2nd Edition. 2011

[6] Burr, RG and Nuseibeh IM. Urinary catheter blockage depends on urine pH, calcium, and rate of flow. Spinal Cord. 35: 521-525. 1997. https://www.nature.com/articles/3100424

[7] Gopferich A. Mechanisms of polymer degradation and erosion. Biomaterials. 17(2): 103-114. 1996. https://www.sciencedirect.com/science/article/pii/0142961296857553

[8] (https://www.hopkinsmedicine.org/health/conditions-and-diseases/vesicoureteral-refluxvur#:~:text=Most%20children%20who%20have%20grade,Surgical%20treatment%20is%20also%20available.)

[9] Chow, Jeanne S., and Annemieke S. Littooij. “Urogenital Pathologies in Children Revisited.” SpringerLink, Springer, Cham, 1 Jan. 1970, link.springer.com/chapter/10.1007/978-3-319-75019-4_7.

[10] Kakizaki H;Moriya K;Ameda K;Shibata T;Tanaka H;Koyanagi T; “Diameter of the External Urethral Sphincter as a Predictor of Detrusor-Sphincter Incoordination in Children: Comparative Study of Voiding Cystourethrography.” The Journal of Urology, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/12544337/.

[11] B;, Reinking LN;Schmidt-Nielsen. “Peristaltic Flow of Urine in the Renal Capillary Collecting Ducts of Hamsters.” Kidney International, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/7300113/.

[12] Kim, Kyung-Wuk, et al. “Analysis of Urine Flow in Three Different Ureter Models.” Computational and Mathematical Methods in Medicine, Hindawi, 4 June 2017, www.hindawi.com/journals/cmmm/2017/5172641/.

[13] Rollino, Cristiana, et al. “Vesicoureteral Reflux in Adults.” Giornale Italiano Di Nefrologia : Organo Ufficiale Della Societa Italiana Di Nefrologia, U.S. National Library of Medicine, 2011, www.ncbi.nlm.nih.gov/pubmed/22167611.

[14] Milanesi, Rafaela, and Rita Catalina Aquino Caregnato. “Intra-Abdominal Pressure: an Integrative Review.” Einstein (Sao Paulo, Brazil), Instituto Israelita De Ensino e Pesquisa Albert Einstein, 2016, www.ncbi.nlm.nih.gov/pmc/articles/PMC5234758/.

[15] “Megaureter & Ureter.” Cleveland Clinic, my.clevelandclinic.org/health/diseases/16305-megaureter.

Vesiscoureteral reflux(VUR) is the condition where urine flows backwards from the bladder into the ureters. It is typically diagnosed in young children, but can affect people through adulthood. Though sometimes the condition corrects itself as the ureters grow, a side effect of VUR is the frequent development of urinary tract infections, which, when untreated, can lead to kidney damage.

There are two types of VUR, primary and secondary. Primary VUR is caused when there is an anatomical defect in the junction between the bladder and the ureters, which does not prevent backflow properly. The secondary VUR is due to the bladder filling up too much, either due to blockages or failure of the bladder muscle and nerves. Both are graded on a 1-5 level scale, with 5 being the most severe. The severity is graded on how far the backflow of urine flows up the ureters. Severe complications of kidney damage due to VUR include failure, scarring, and high blood pressure.

Existing treatments aim at the prevention of UTIs and kidney damage, with both surgical and managerial options. *Managerial treatment relies on antibiotic treatment of UTIs, which can lead to antibiotic resistance over time. Surgical repair is typically for higher grades of the condition and includes endoscopic, laproscopic, and open techniques, requiring hospital stays. Typically children with severe grades of VUR have pre-existing conditions which make surgical risks higher, so there is a need for a less invasive procedure to correct high-grade VUR.