Pediatric Device Clinical Trials Activity: 1999-2022.

OBJECTIVES: This study assessed the state of pediatric medical device (PMD) development by comparing PMD clinical trials to pediatric trials evaluating drugs and biologics, from 1999 to 2022. METHODS: The site www.clinicaltrials.gov was used to identify and quantify both PMD clinical trials and pediatric trials for drugs and biologics. Clinical specialty was also assessed. The institutions included were the 7 children's hospitals primarily affiliated with the Food and Drug Administration (FDA) Pediatric Device Consortia (PDC) grant program between 2018 and 2023. For a national comparison, an additional search assessed PMD trials across all US medical institutions. RESULTS: A total of 243 PMD clinical trials were identified at the FDA-PDC institutions on the basis of the year of initiation; the average number of PMD trials initiated per year per institution was 1.5 from 1999 to 2022. However, PMD trials significantly increased during the period 2014 to 2022 compared with 1999 to 2013 (P < .001); the rate of initiation of drug and biologic pediatric trials demonstrated no significant differences between these time periods. A national survey of all institutions initiating PMD trials, and drugs and biologics trials, identified 1885 PMD trials out of a total 12 943. A comparable trend was noted in the national survey with initiation of PMD trials increasing significantly from 2014 to 2022 (P < .001), compared with 1999 to 2013, whereas the rate of initiation of drug and biologic trials during these periods did not demonstrate a significant change. CONCLUSIONS: Although pediatric clinical trial initiation for drugs and biologics remained stable from 1999 to 2022, the rate of new PMD trials significantly increased during the period 2014 to 2022 at FDA-PDC institutions and nationally.

Barriers to and facilitators of paediatric medical device innovation: a scoping review protocol.

INTRODUCTION: The development of paediatric medical devices continues to lag adult medical devices and contributes to issues of inequity, safety, quality and patient outcomes. New legislation and funding mechanisms have been introduced over the past two decades, but the gap remains. Clinical trials have been identified as a pain point, but components of effective clinical research infrastructure are poorly understood. As part of a multimodal research strategy, the Pediatric Device Consortia (PDC) will conduct a scoping review to better understand infrastructural barriers to and facilitators of paediatric medical device clinical research identified in the health sciences literature. METHODS AND ANALYSIS: The following databases will be included for this review: Medline, Embase, Cochrane CENTRAL, Web of Science and IEEE Xplore. Additional grey literature will be sought out through Google Scholar and reviewing the citations of included studies. Included studies will discuss medical devices according to the U.S. Food and Drug Administration classification, focus on the paediatric population (ages 0-21 years) and involve human premarket or postmarket research. All study types that were published in 2007-present in English, Spanish, French or Italian will be included. Using Covidence web-based software, two independent reviewers will screen the resulting titles, abstracts and the full text of potential studies. Conflicts will be resolved by the primary investigator during both phases. REDCap will be used for quantitative and qualitative data charting, generating data tables and narrative synthesis. ETHICS AND DISSEMINATION: This research did not require research ethics board consideration as it does not involve human participants and all data will be collected from published literature. We will share our findings through peer-reviewed manuscripts, clinical and research conference presentations and professional networks available to the PDC. STUDY REGISTRATION: Open Science Framework (https://osf.io/k72bn).

Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation.

Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of Piezo1 in lymphatics or systemic administration of Yoda1 in mice with hydrocephalus or Down syndrome resulted in a notable decrease in pathological CSF accumulation, ventricular enlargement and other associated disease symptoms. Together, our study highlights the importance of Piezo1-mediated lymphatic mechanotransduction in maintaining brain fluid drainage and identifies Piezo1 as a promising therapeutic target for treating excessive CSF accumulation and ventricular enlargement.

Fetal bladder morphology as a predictor of outcome in fetal lower urinary tract obstruction.

OBJECTIVE: We evaluate survival of fetuses with severe Lower Urinary Tract Obstruction (LUTO) based on bladder morphology. We hypothesize that fetuses with a "floppy" appearing bladder on initial prenatal ultrasound will have worse infant outcomes than fetuses with full/rounded bladders. METHOD: We retrospectively reviewed all cases of LUTO evaluated in our fetal center between January 2013 and December 2021. Ultrasonographic assessment, renal biochemistry, and bladder refilling contributed to a "favorable" or "unfavorable" evaluation. Bladder morphology on initial ultrasound was classified as "floppy" or "full/rounded." Vesicoamniotic shunting was offered for favorably evaluated fetuses. Baseline demographics, ultrasound parameters, prenatal evaluations of fetal renal function, and infant outcomes were collected. Fetuses diagnosed with severe LUTO were included in analysis using descriptive statistics. The primary outcome measured was survival at 6 months of life. RESULTS: 104 LUTO patients were evaluated; 24 were included in analysis. Infant survival rate at 6 months was 60% for rounded bladders and 0% for floppy bladders (p = 0.003). Bladder refill adequacy was lower in fetuses with floppy bladders compared with rounded bladders (p value < 0.00001). CONCLUSION: We propose that bladder morphology in fetuses with severe LUTO may be a prognostication factor for predicting infant outcomes and provides a valuable, noninvasive assessment tool.

Evaluating the utility of routine urine culture and antibiotic treatment in children with neurogenic bladder undergoing intradetrusor OnabotulinumtoxinA injection.

INTRODUCTION: OnabotulinumtoxinA is used as treatment for refractory idiopathic and neurogenic detrusor overactivity in children. Many patients perform intermittent self-catheterization and therefore have higher rates of asymptomatic bacteriuria, which may increase their risk of symptomatic urinary tract infection (UTI) following treatment. Multiple injections are often needed due to the short-term efficacy of onabotulinumtoxinA treatment, which may also increase the risk of UTI. OBJECTIVE: We aim to evaluate whether a sterile urinary tract is necessary to decrease the risk of postoperative UTI in pediatric patients treated with onabotulinumtoxinA. STUDY DESIGN: A retrospective review of patients undergoing intradetrusor onabotulinumtoxinA injection from 2014 to 2021 was performed. Demographic data, clinical characteristics, antibiotic treatment and culture results were collected. A positive urine culture was defined as ≥ 103 CFU/ml of uropathogenic bacteria. Our primary outcome was symptomatic UTI within 14 days of the procedure. RESULTS: 103 patients underwent 158 treatments with onabotulinumtoxinA. The incidence of postoperative UTI was 3.2%. The incidence of symptomatic postoperative UTI in patients with asymptomatic bacteriuria compared to those with sterile urine was not significantly different (3.8% vs 0%, p = 0.57). Obtaining a preoperative urinalysis or urine culture did not affect the incidence of postoperative UTI (p = 0.54). The number needed to treat with antibiotics to prevent one postoperative UTI was 27. The incidence of postoperative UTI was highest in patients with low-risk bladders (p = 0.043). Prior history of multi-drug resistant UTI was a risk factor for postoperative UTI (p = 0.048). DISCUSSION: For children undergoing onabotulinumtoxinA injection, there are no evidence-based recommendations regarding antibiotic prophylaxis and the need to screen for and treat asymptomatic bacteruria prior to treatment. Our study addresses this important clinical question, and shows no difference in the rate of postoperative UTI between patients with asymptomatic bacteriuria and those with sterile urine. Patients with a history of multi-drug resistant UTI are at increased risk of symptomatic postoperative UTI and may benefit from preoperative urine testing and treatment. Limitations of our retrospective study include its small sample size in the face of such a low incidence of our primary outcome. CONCLUSIONS: The risk of UTI following onabotulinumtoxinA injection in children is low. The presence of sterile urine at the time of surgery does not significantly decrease the risk of postoperative UTI. Routine treatment of asymptomatic bacteriuria prior to surgery results in a large number of patients receiving unnecessary antibiotics. As a result, we recommend against preoperative urine testing for most asymptomatic patients.

Ureteral stricture after pediatric kidney transplantation: Is there a role for percutaneous antegrade ureteroplasty?

INTRODUCTION: Ureteral obstruction following pediatric kidney transplantation occurs in 5-8% of cases. We describe our experience with percutaneous antegrade ureteroplasty for the treatment of ureteral stricture in pediatric kidney transplant patients. METHODS: We retrospectively reviewed all pediatric kidney transplantation patients who presented with ureteral stricture and underwent percutaneous antegrade ureteroplasty at our institution from July 2009 to July 2021. Variables included patient demographics, timing of presentation, location and extent of stricture, ureteroplasty technique and clinical outcomes. Our primary outcome was persistent obstruction of the kidney transplant. RESULTS: Twelve patients met inclusion criteria (4.2% of all transplants). Median age at time of ureteroplasty was 11.5 years (range: 3-17.5 years). Median time from kidney transplantation to ureteroplasty was 3 months. Patency was maintained in 50% of patients. Seven patients (58.3%) required additional surgery. Four patients developed vesicoureteral reflux. Patients with persistent obstruction had a longer time from transplant to ureteroplasty compared to those who achieved patency (19.3 vs 1.3 months, p = 0.0163). Of those treated within 6 months after transplantation, two patients (25%) required surgery for persistent obstruction (p = 0.06). All patients treated >1 year after transplantation had persistent obstruction following ureteroplasty (p = 0.06). CONCLUSION: Percutaneous antegrade ureteroplasty can be considered a viable minimally invasive treatment option for pediatric patients who develop early ureteral obstruction (<6 months) following kidney transplantation. In patients who are successfully treated with ureteroplasty, 67% can develop vesicoureteral reflux into the transplant kidney. Patients who fail early percutaneous ureteroplasty or develop obstruction >1 year after transplantation are best managed with surgical intervention.

Robotic partial nephrectomy in the pediatric population: Cumulative experience at a large pediatric hospital.

INTRODUCTION: Robotic partial nephrectomy is a complex minimally invasive procedure that addresses the intricate anatomy of renal masses while maximizing preservation of renal function. However, while common in adults, the evolution toward these minimally invasive procedures for children has been slow due to the anticipated technical difficulties in pediatric-sized working spaces. We present our technique and our experience with pediatric robotic partial nephrectomies that were performed with our adult urology colleagues at a large free-standing children's hospital. METHODS: The video describes our technique for a robotic right-sided partial nephrectomy in a 14-month-old male patient. The video highlights several steps of the procedure including positioning and port placement, tumor resection, and renorrhaphy. RESULTS: Six pediatric patients underwent robotic partial nephrectomy with our associated adult urologic surgeons from January 2019 to January 2021. The surgical pathology revealed both benign as well as malignant diagnoses. CONCLUSION: Robotic partial nephrectomy is a feasible minimally invasive procedure in children. The collaboration with adult minimally invasive urologic surgeons with extensive adult procedural experience is recommended to avoid potential complications with this technically challenging procedure in pediatric patients. Pediatric strategies for robotic port placement are often needed to accommodate the smaller size of pediatric patients as well as tumor size.

The ChorioAnchor: Design and Testing of a Novel Chorioamniotic Anchoring Device to Enable Percutaneous Fetoscopic Surgery.

INTRODUCTION: Percutaneous fetoscopic surgery is hampered by an increased risk of preterm prelabor rupture of membranes (PPROM). Recent surgical techniques have shown that suturing the chorioamniotic membranes following laparotomy and uterine exteriorization is associated with a lower risk of PPROM compared to percutaneous in utero surgery. This study presents the ChorioAnchor, a novel resorbable device that percutaneously anchors the chorioamniotic membranes to the uterine wall. METHODS: Human factors testing and peel tests were used to simulate the worst-case in-use loading conditions, establishing the device strength requirements. Tensile testing was used to measure the time-zero strength of the device. Porcine cadaver testing was used to examine ultrasound visibility and acute handling characteristics. Short-term host response was examined through an acute 7-day implantation study in a rabbit model. RESULTS: With a time-zero tensile strength of 47 N, the ChorioAnchor exceeded the established 4 N strength requirement. Both the ChorioAnchor and delivery device were seen to be clearly visible under ultrasound imaging. Short-term host response to the device was well within the range expected for this type of device. CONCLUSION: The ChorioAnchor meets its engineering requirements in the early stages of implantation. Future studies will examine the kinetics of degradation of the device in vitro and in vivo.

Is urgent surgical management necessary for priapism in pediatric patients with hematologic conditions?

INTRODUCTION: Acute priapism is usually considered a medical emergency that warrants prompt urologic evaluation and treatment. Efforts have been made to determine the optimal management strategy for pediatric priapism. OBJECTIVE: The aim of this study is to assess differences in conservative, minimally-invasive, and operative management of acute priapism in the pediatric population. STUDY DESIGN: A retrospective study of pediatric patients with acute priapism from 2015 to 2021 at a single tertiary care children's hospital was conducted. Conservative, minimally-invasive, and operative approaches for the priapism episodes during these hospital encounters were analyzed. RESULTS: Thirty-nine patients were identified with a total of 61 cases of acute pediatric priapism were evaluated in the study period. Eight-three percent of patients were African-Americans, and 72% of patients had a history of sickle cell disease. Oxygen therapy (P = 0.001) and hydration with intravenous fluids (P = 0.00318) were more commonly utilized for hematologic-associated cases compared to other etiologies. For priapism episodes of hematologic etiology, 18 (40.0%) and 18 (40.0%) patients received phenylephrine injection and aspiration/irrigation (e.g., minimally-invasive therapy), respectively, while for the other causes of priapism, three (18.8%) and four (25.0%) received phenylephrine injection and aspiration/irrigation (e.g., minimally-invasive), respectively. Conservative and minimally-invasive treatment resulted in complete resolution of priapism in 27 (60%) and 16 (35.5%) patients with hematologic-associated priapism while 12 (75%) and 1 (6.3%) patients with other etiologies had resolution of priapism with conservative and minimally-invasive treatment, respectively. One patient received shunting in the hematologic group while two patients received shunting in the non-hematologic group (P = 0.1031). DISCUSSION: Hematologic disorders are the most common causes of priapism in children and adolescents. An overwhelming majority of priapism events in the pediatric population can be managed with conservative therapies including oxygenation and intravenous hydration as well as minimally-invasive procedures such as corporal aspiration, irrigation and/or injections. The utilization of corporal shunting, anesthesia, and hospital resources is infrequently necessary for pediatric priapism episodes. CONCLUSION: While urgent surgical management is often performed in the adult population, a minimally-invasive management strategy can be implemented in the pediatric population where an extended period of conservative management that avoids operative management and general anesthesia is effective.

Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion.

BACKGROUND: Mutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion. METHODS: Various mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration. RESULTS: Piezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development. CONCLUSIONS: Piezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.

Development and Validation of a Scoring System for Assessment of Clinical Failure after Pediatric Robot-Assisted Laparoscopic Extravesical Ureteral Reimplantation: A Multi-Center Study.

We aimed to develop and validate a scoring system as an objective assessment tool for predicting clinical failure after pediatric robotic extravesical ureteral reimplantation. Data for this multi-institutional retrospective cohort was obtained from two tertiary referral hospitals. We defined clinical failure as incomplete radiographic resolution or post-operative febrile UTI. Patients were stratified into low, intermediate, and high-risk groups according to the score. External validation was performed using the model projected to the external validation cohort. An amount of 115 renal units in the development cohort and 46 renal units in the validation cohort were analyzed. The prediction score was calculated with weighted points to each variable according to their regression coefficient as age (year) + BMI + BBD times 10 + VUR grade times 7 + console time (h) + hospital stay times 6. The C-index of our scoring system was 0.850 and 0.770 in the development and validation cohorts, respectively. Clinical failure was significantly different among risk groups: 0% (low-risk), 3.3% (intermediate-risk), and 22.2% (high-risk) (p = 0.004) in the development cohort. A novel scoring system using multiple pre- and intra-operative variables provides a prediction of children at risk of failure after robotic extravesical ureteral reimplantation.

Opportunities for Regulatory Changes to Promote Pediatric Device Innovation in the United States: Joint Recommendations From Pediatric Innovator Roundtables.

OBJECTIVE: The purpose of this report is to provide insight from pediatric stakeholders with a shared desire to facilitate a revision of the current United States regulatory pathways for the development of pediatric healthcare devices. METHODS: On August 5, 2020, a group of innovators, engineers, professors and clinicians met to discuss challenges and opportunities for the development of new medical devices for pediatric health and the importance of creating a regulatory environment that encourages and accelerates the research and development of such devices. On January 6, 2021, this group joined regulatory experts at a follow-up meeting. RESULTS: One of the primary issues identified was the need to present decision-makers with opportunities that change the return-on-investment balance between adult and pediatric devices to promote investment in pediatric devices. DISCUSSION/CONCLUSION: Several proposed strategies were discussed, and these strategies can be divided into two broad categories: 1. Removal of real and perceived barriers to pediatric device innovation; 2. Increasing incentives for pediatric device innovation.

Novel scoring system for determining fetal candidacy for prenatal intervention for severe congenital lower urinary tract obstruction.

OBJECTIVES: To evaluate a novel scoring system that combines several prenatal parameters for selecting ideal candidates for fetal intervention, and for predicting postnatal survival in patients with severe fetal lower urinary tract obstruction (LUTO). METHODS: We retrospectively reviewed all cases of severe LUTO evaluated for fetal intervention in a single large fetal center between January 2013 and December 2017. A scoring system for determining fetal candidacy for intervention was retrospectively developed based on postnatal outcomes. The proposed scoring system included fetal urinary biochemistry, renal ultrasound parameters, initial bladder volume, and degree of bladder refill. Relevant demographic characteristics, ultrasound reports and laboratory results were reviewed. Receiver operating characteristic (ROC) curves were used to select the cut-off values for initial bladder volume and degree of bladder refill and to evaluate the performance of the scoring system in predicting postnatal death. RESULTS: Of the 79 LUTO patients evaluated, 31 were eligible for the study. The overall 6-month postnatal survival was 64.5 % (20/31). A scoring system (0-8) was suggested with 2 points for unfavorable biochemistry, 4 points for ultrasound evidence of dysplastic kidneys, 1 point for inadequate initial bladder volume and 1 point for inadequate bladder refill. Scores>3 (N = 7) were associated with 0 % 6-month survival. The ROC curve for predicting postnatal mortality showed area under curve (AUC) of 0.82 (95 % CI 0.65-0.99). Subgroup analysis within subjects who underwent fetal intervention (N = 22) also confirmed the significance of the distribution of the scoring system between groups who survived and those who did not after adjustment for GA at delivery (p = 0.01). CONCLUSION: We propose a novel scoring system for antenatal evaluation of patients with severe LUTO which may be useful in selecting those candidates most appropriate for intervention and in counseling parents about predicted postnatal outcome.

Improved Low-Glucose Predictive Alerts Based on Sustained Hypoglycemia: Model Development and Validation Study.

BACKGROUND: Predictive alerts for impending hypoglycemic events enable persons with type 1 diabetes to take preventive actions and avoid serious consequences. OBJECTIVE: This study aimed to develop a prediction model for hypoglycemic events with a low false alert rate, high sensitivity and specificity, and good generalizability to new patients and time periods. METHODS: Performance improvement by focusing on sustained hypoglycemic events, defined as glucose values less than 70 mg/dL for at least 15 minutes, was explored. Two different modeling approaches were considered: (1) a classification-based method to directly predict sustained hypoglycemic events, and (2) a regression-based prediction of glucose at multiple time points in the prediction horizon and subsequent inference of sustained hypoglycemia. To address the generalizability and robustness of the model, two different validation mechanisms were considered: (1) patient-based validation (model performance was evaluated on new patients), and (2) time-based validation (model performance was evaluated on new time periods). RESULTS: This study utilized data from 110 patients over 30-90 days comprising 1.6 million continuous glucose monitoring values under normal living conditions. The model accurately predicted sustained events with >97% sensitivity and specificity for both 30- and 60-minute prediction horizons. The false alert rate was kept to <25%. The results were consistent across patient- and time-based validation strategies. CONCLUSIONS: Providing alerts focused on sustained events instead of all hypoglycemic events reduces the false alert rate and improves sensitivity and specificity. It also results in models that have better generalizability to new patients and time periods.

Testicular Myofibroma in Children: A Case Report and Review of the Literature.

Testicular tumors are rare in the prepubertal population and often are germ cell tumors. Myofibroma is a rare spindle cell neoplasm composed of myofibroblasts, which are intermediate cells between fibroblasts and smooth muscle cells. Only two prepubertal testicular myofibromas have been previously reported. While cryptorchidism is a risk factor for testicular germ cell tumors, the exact etiology of testicular myofibroma is unknown. We report a case of testicular myofibroma in a six-year-old male with a history of undescended testes, as well as a review of the literature. This case suggests a possible connection between undescended testes and testicular myofibroma.

Advancing pediatric medical device development via non-dilutive NIH SBIR/STTR grant funding.

INTRODUCTION: A shortage of medical devices designed for children persists due to the smaller pediatric population and market factors. Furthermore, pediatric device development is challenging due to the limited available funding sources. We describe our experience with pediatric device projects that successfully received federal grant support towards commercializing the devices that can serve as a guide for future innovators. METHODS: The developmental pathways of pediatric device projects at a tertiary-care children's hospital that received NIH SBIR/STTR funding between 2016-2019 were reviewed. The clinical problems, designs, specific aims, and development phase were delineated. RESULTS: Pediatric faculty successfully secured NIH SBIR/STTR funding for five pediatric devices via qualified small business concerns (SBC's). Three projects were initiated in the capstone engineering design programs and developed further at two affiliated engineering schools, while the other two projects were developed in the faculty members' labs. Four projects received funding via established SBC's, while one was awarded funding via a newly established SBC. CONCLUSION: NIH SBIR/STTR grants are an essential source of external non-dilutive funding for pediatric device innovation and especially for academic-initiated projects. This funding can provide needed early-stage support to facilitate commercialization. In addition, these grants can serve as achievable accomplishments for pediatric faculty portfolios toward academic promotion. Our experience shows that it is possible to build a robust innovation ecosystem comprised of academic faculty (clinical/engineering) collaborating with local device development companies while jointly implementing a product development strategy leveraging NIH SBIR/STTR funding for critical translational research phases of pediatric device development.