Engineered modular porous scaffolds for enhanced vascular integration and long-term tissue grafting

The National Institute of Child Health and Human Development awarded Regents of the University of Michigan $603,157 on September 1, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to develop engineered modular porous scaffolds for enhanced vascular integration in long-term tissue grafting.

The award funds development of annealed porous grafts—next-generation ovarian tissue implants designed to restore ovarian endocrine function in patients with premature ovarian insufficiency, a common consequence of anti-cancer treatments. The project leverages microporous annealed particles hydrogel technology to address key challenges in ovarian tissue transplantation: poor graft viability, inadequate vascularization, premature follicle activation, and short graft longevity. Work proceeds in three aims. Aim 1 enhances bidirectional nutrient and signaling exchange by integrating capillary-scale vascular networks and tuning microgel parameters to achieve rapid, stable revascularization and functional integration of ovarian tissue. Aim 2 investigates controlled-release systems within the hydrogel matrix, focusing on sustained delivery of anti-mullerian hormone to prevent premature follicle activation and prolong graft functional lifespan. Aim 3 engineers temporally staged proteolytic degradation within distinct scaffold subdomains to enable sequential follicle activation and extend graft longevity by preventing premature depletion of the follicular pool.

Performance occurs at Ann Arbor, Michigan, with a period of performance from September 1, 2026 through May 31, 2031. The award is classified as a Project Grant.

Abstract

Microporous annealed particles (map) hydrogels offer a sophisticated, modular platform for engineering implantable tissue grafts with precisely tunable properties and functionality. Leveraging recent advances in microgel design and annealing, we propose to develop annealed porous grafts (APGS)-next-generation ovarian tissue implants designed to restore ovarian endocrine function in patients with premature ovarian insufficiency (POI), a common and devastating consequence of anti-cancer treatments. Through precise control over microgel composition and architecture, map hydrogels enable the modular integration of bioactive cues and engineered structures that directly address key challenges in ovarian tissue transplantation: poor graft viability, poor vascularization, premature follicle activation, and short graft longevity. In aim 1, we will harness the customizable porosity and biofunctionality of APGS to enhance bidirectional nutrient and signaling exchange, support robust tissue survival, and actively promote vascular outgrowth. By integrating capillary-scale vascular networks and tuning microgel parameters, we seek to achieve rapid, stable revascularization and functional integration of ovarian tissue. Aim 2 investigates the incorporation of controlled release systems within the hydrogel matrix, focusing on sustained delivery of anti-mullerian hormone (AMH). By recapitulating physiological AMH signaling, we aim to prevent premature activation of primordial follicles and prolong the functional lifespan of the tissue grafts. In aim 3, we will engineer temporally staged proteolytic degradation within distinct APG subdomains, enabling sequential follicle activation. This strategy is designed to mimic natural ovarian dynamics and extend graft longevity by preventing premature depletion of the follicular pool. Collectively, this bioengineering-driven approach seeks to realize clinically translatable, functional "artificial ovary" grafts for restoring fertility and endocrine function in young female cancer survivors with POI and also advances the field of tissue engineering toward more sophisticated, adaptable, and life-changing therapeutic platforms.