Combining Cryogel Architecture and Macromolecular Crowding-Enhanced Extracellular Matrix Cues to Mimic the Bone Marrow Niche

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Laura Martínez-Vidal - , Leibniz Institute of Polymer Research Dresden, TUD Dresden University of Technology, Vita-Salute San Raffaele University (Author)
  • Valentina Magno - , Leibniz Institute of Polymer Research Dresden (Author)
  • Petra B. Welzel - , Leibniz Institute of Polymer Research Dresden (Author)
  • Jens Friedrichs - , Leibniz Institute of Polymer Research Dresden (Author)
  • Martin Bornhäuser - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Carsten Werner - , Center for Regenerative Therapies Dresden, Chair of Biofunctional Polymer Materials, Leibniz Institute of Polymer Research Dresden (Author)

Abstract

Transplantation of hematopoietic stem cells (HSCs)—rare cells that can self-renew and differentiate into cells of all hematopoietic lineages—is an important treatment option for patients with hematologic diseases. Key to the regenerative potential of HSCs is their natural in vivo microenvironment—the bone marrow niche—but in vitro engineering approaches to recapitulate the biochemical and biophysical properties of the bone marrow niche are still insufficiently explored. Herein, modular macroporous cryogels, mimicking the natural 3D architecture of trabecular bone, are seeded with human bone marrow-derived mesenchymal stromal cells and decellularized to generate tissue-specific extracellular matrix (ECM)-decorated scaffolds. To recapitulate the physiological concentration of biomolecules in bone marrow, the cell culture medium is supplemented with macromolecular crowders that modulate the composition, ultrastructure, and mechanical properties of the cell-deposited ECM. The ECM-coated cryogel scaffolds generated under crowding conditions exhibit physicochemical properties similar to those of the endosteal niche of the bone marrow. The ECM-functionalized cryogels presented could be used in the future for the ex vivo expansion of HSCs for transplantation and may also aid in the development of more realistic hematological disease models.

Details

Original languageEnglish
Article number2200348
Number of pages13
JournalMacromolecular Chemistry and Physics
Volume224 (2023)
Issue number1
Publication statusPublished - 4 Dec 2022
Peer-reviewedYes

External IDs

ORCID /0000-0003-0189-3448/work/161890259

Keywords

Keywords

  • bone marrow niches, decellularization, macromolecular crowding, macroporous cryogels, mesenchymal stem cells