Sustained 9-CIS retinoic acid-eluting nanofiber scaffolds for enhanced lymphatic regeneration and lymphedema treatment

The National Heart, Lung, and Blood Institute awarded Matregenix Inc. $314,211 on September 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to develop biodegradable, drug-eluting nanofiber scaffolds for lymphatic regeneration and lymphedema treatment.

Matregenix will fabricate flexible, tubular scaffolds composed of amino acid-based poly(ester urea) designed to deliver sustained, localized 9-cis retinoic acid to promote lymphangiogenesis. Phase I objectives include optimizing the scaffold formulation to achieve target mechanical properties and sustained 9-cis retinoic acid release over four to eight weeks; evaluating scaffold biocompatibility and bioactivity using human lymphatic endothelial cells in vitro, assessing viability, proliferation, migration, and tube formation; and assessing therapeutic efficacy in a murine hindlimb lymphedema model through imaging, histology, and functional endpoints including limb volume reduction and lymphatic vessel regeneration. The Phase I work will identify a lead scaffold formulation and establish proof-of-concept efficacy in vitro and in vivo to support advancement to Phase II studies.

Performance period is September 1, 2026, through August 31, 2027. Work is performed in Irvine, California.

Abstract

Lymphedema is a progressive and often irreversible condition characterized by impaired lymphatic drainage, chronic limb swelling, pain, and recurrent infections, affecting over 250 million individuals globally and more than 3 million in the united states. Despite its widespread impact and rising incidence in cancer survivors, no FDA-approved drug therapies exist to restore lymphatic function, and current treatment options-including compression garments and manual lymphatic drainage-are labor-intensive, lifelong, and fail to address the root cause of lymphatic vessel damage. To overcome this challenge, we propose the development of a biodegradable, drug-eluting nanofiber scaffold composed of amino acid-based poly(ester urea) (PEU) designed to deliver sustained, localized 9-CIS retinoic acid (9-CIS RA), a small molecule known to promote lymphangiogenesis. Leveraging matregenix's proprietary electrospinning platform, we will fabricate flexible, tubular scaffolds (~1-2 MM inner diameter) that provide both structural support and biochemical signaling to guide lymphatic regeneration. Our phase I study has three aims: (1) optimize the scaffold formulation to achieve target mechanical properties and sustained 9-CIS RA release over 4-8 weeks; (2) evaluate scaffold biocompatibility and bioactivity using human lymphatic endothelial cells in vitro, assessing viability, proliferation, migration, and tube formation; and (3) assess therapeutic efficacy in a murine hindlimb lymphedema model through imaging, histology, and functional endpoints such as limb volume reduction and lymphatic vessel regeneration. During phase I, we will identify a lead scaffold formulation and demonstrate proof-of-concept efficacy in vitro and in vivo. This will set the stage for a phase II program focused on large- animal studies, GLP-compliant biocompatibility testing, and regulatory engagement. We will initiate a pre- submission meeting with the FDA to determine the optimal regulatory pathway and define the required studies to support clearance or approval. This project represents a first-in-class approach to lymphatic repair, combining bioengineered structure with regenerative drug delivery, and has the potential to transform the standard of care for lymphedema by offering a functional, curative solution rather than lifelong symptom management.