Biomaterials-integrated microphysiological bone marrow chip model

The National Heart, Lung, and Blood Institute awarded the University of Massachusetts $425,971 under the Cardiovascular Diseases Research program (CFDA 93.837) on July 6, 2026, to develop a biomaterials-integrated microphysiological bone marrow chip model.

The award funds development of a silicon-based perfusion chip platform that integrates demineralized bone paper and inverted colloidal crystal hydrogel scaffolds to recapitulate the structural and functional interdependence of bone and bone marrow compartments. The model aims to enable dynamic analysis of hematopoietic stem cell behavior by replicating two anatomically distinct yet functionally interdependent niches: the endosteal niche supporting dormancy and self-renewal of long-term hematopoietic stem cells, and the vascular niche supporting actively cycling short-term hematopoietic stem cells and ongoing hematopoiesis. The research involves seeding bone marrow stromal cells and osteoblasts into their respective biomaterials to validate niche-specific stromal phenotypes and recapitulate bone remodeling, then introducing CD34 hematopoietic stem cells to assess how integrated versus separated configurations of bone and marrow compartments differentially regulate hematopoietic stem cell behavior. Validation includes recapitulation of autologous hematopoietic stem cell transplantation scenarios following preconditioning.

The award is classified as a Project Grant. Performance occurs in Hadley, Massachusetts, with a period of performance from July 6, 2026, through June 30, 2028.

Abstract

Trabecular bone marrow contains two anatomically distinct yet functionally interdependent niches that support hematopoietic stem cells (hscs): the endosteal niche, which promotes dormancy and self-renewal of long-term hscs, and the vascular niche, which supports actively cycling short-term hscs and ongoing hematopoiesis. These compartments coordinate bone remodeling and hematopoiesis, but the mechanisms underlying their integration remain poorly understood due to the anatomical inaccessibility of the bone cavity and the lack of physiologically relevant preclinical models. This proposal aims to develop a biomaterials-integrated bone-marrow microphysiological system (MPS) that recapitulates the structural and functional interdependence of the bone and marrow compartments and enables dynamic analysis of HSC behavior. The platform integrates two advanced biomaterials: demineralized bone paper (DBP), an osteoid-like matrix that supports osteoblast mineralization and osteoclast-mediated remodeling, and an inverted colloidal crystal (ICC) hydrogel scaffold that mimics the sinusoidal architecture of marrow and supports stromal-hematopoietic interactions. The central hypothesis is that integrating these components within a silicon-based perfusion chip will enable high-fidelity modeling of dynamic bone marrow niche processes with precise experimental control and microscopic access. Aim 1 will establish the bone-marrow MPS by seeding bmscs and osteoblasts into their respective biomaterials, validating niche-specific stromal phenotypes, and recapitulating bone remodeling. CD34⁺ hscs will then be introduced to assess how integrated versus separated configurations of the bone and marrow compartments differentially regulate HSC behavior. Aim 2 will validate the bone-marrow MPS by recapitulating autologous HSC transplantation scenarios following preconditioning. Donor-matched bone-marrow MPS units will be established, and hscs derived from a different donor will be introduced with and without fractionated irradiation. By comparing HSC engraftment outcomes, the MPS's ability to replicate known features of clinical transplantation will be demonstrated. This human-relevant bone-marrow MPS platform will provide new insights into bone-marrow crosstalk, preconditioning regimens, and HSC processes. IT offers a scalable, high-resolution system for studying hematopoiesis, transplantation biology, and therapeutic interventions-aligned with NIH priorities in the nosi: bold new bioengineering research for heart, lung, blood, and sleep disorders.