Biologically-engineered pediatric conduits that grow

Abstract

We have developed a biologically-engineered tube of cell-produced collagenous matrix, which is allogeneic upon a decellularization performed prior to implantation and thus “off-the-shelf.” It is manufactured from donor dermal fibroblasts entrapped in and remodeling a sacrificial fibrin hydrogel tube that is then decellularized using sequential detergent treatments. The resulting cell-produced matrix tube possesses physiological strength, compliance, and alignment (circumferential). It exhibits somatic growth over 52 weeks when implanted as an interpositional pulmonary artery graft in young lambs because the matrix becomes a living tissue with the recipient’s cells post-implantation, including spontaneous endothelium formation (Syedain et al., Nat Comms 2016, Comms Med 2024).  Using the concept of a tubular heart valve, where the tube collapses inward with back-pressure between 3 equi-spaced constraints placed around the periphery to create one-way valve action, we have created a valved conduit that exhibits normal increase of diameter and indications of leaflet growth as well as sustained valve function over 52 weeks in growing lambs (Syedain et al., Sci Transl Med 2021, Cardiovasc Res 2025), with the prospect of indefinite durability because it is recellularizing. Related clinical translation and commercialization activities are at advanced stages. Acknowledgement to NIH R01 HL107572 and DoD TTDA W81XWH2210489 (to R.T.T).