Biostage, Inc. — Department of Health and Human Services SBIR Phase I: NICHD

Description

ABSTRACT Esophageal AtresiaEAis a congenital birth defect characterized by a discontinuity of the esophagusEach year several thousand children are born within the EA spectrumBabies born with EA have trouble feedingand require a procedure to correct the abnormalityThe best treatment for EA is surgery reconnecting the two ends of the esophagus to each otherIn some childrenhoweverthe gap between the two esophageal ends is too long to be easily connectedThis condition is known as long gap esophageal atresiaLGEACurrent surgical options available for the treatment of LGEA focus upon either the replacement of the esophageal tissue with other autologous tissueor mechanically stretching the current esophageal tissue to bridge the gapAlthough there are several techniques availablethere is little consensus about the optimal repair of LGEAIn additionthe infrequent occurrence of LGEA also means that development of improved techniques is greatly hamperedThusthere is clearly an unmet clinical need for effective methods of esophageal repairTo answer this unmet medical needBiostage Inc and our academic partners at Connecticut Children s Medical CenterCT Children spropose to develop a novel tissue engineered esophageal implant that combines a synthetic scaffold with patient derived stem cellsas a treatment for LGEABiostageandapos s Cellspan Esophageal Implant has the unique ability to induce the bodyandapos s own repair mechanismwhile providing spatial cues to assist regenerationPrevious preclinical studies at Biostage have established that full thickness circumferential esophageal defects can be treated by implanting the CEI in an adult pig modelStudies at the Finck laboratory have shown that autologous epithelial cell seeded scaffold can be utilized to treat similar defects in a piglet modelBased on these findings we plan to develop a novel tissue engineered esophageal implant to address LGEA in newbornsThe goal of the project will be establishing long term efficacy of our CEI as an esophageal replacement in piglet pediatric modelPhase I will include the preparation of CEI with size relevant for a pediatric modelSpecific AimWe will create a CEI by seeding piglet cells onD scaffold in bioreactor and analyze the CEI to determine cell viabilitycell penetration and cell functionality in terms of MSC marker expression and cytokine secretion profilesIn Phase II we will perform a short term in vivo feasibility study of CEI as an esophageal replacement in a piglet modelSpecific AimOnce we confirm that no acute adverse effects arise due to animal exposure to the CEIwe will conduct a long term in vivo studySpecific Aimwhere we will follow the growth and development of the tissue in the implant zoneThe ability of the animals to function normally at such longer time scales will be key to assess the use of the CEI as an esophageal treatmentUpon completion of these Aimswe will initiate dialogue with the FDA to obtain pre IND guidance and will carry out pre clinical studies to ensure a clinical path for the use of CEIs as a treatment for pediatric atresiaNARRATIVE long gap esophageal atresiaLGEAis a congenital birth defect characterized by a discontinuity of the esophaguswhere the gap between the two esophageal ends is too long to be easily connected There is little consensus about the optimal repair of LGEA and its infrequent occurrence means that development of improved techniques is greatly hamperedIn this Fast Track SBIR application Biostage is seeking to develop a retrievable autologous bioengineered esophageal implantas a novel treatment for long gap esophageal atresia