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bioRxiv · 10.1101/2022.01.21.477275

Immune-responsive biodegradable scaffolds for enhancing neutrophil regeneration

Kerr, M.·McBride, D.·Johnson, W.·Chumber, A.·Najibi, A.·Seo, B. R.·Stafford, A.·Scadden, D.·Mooney, D.·Shah, N.
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Abstract

Neutrophils are essential effector cells for mediating rapid host defense and their insufficiency arising from therapy-induced side-effects, termed neutropenia, can lead to immunodeficiency-associated complications. In autologous hematopoietic stem cell transplantation (HSCT), neutropenia is a complication that limits therapeutic efficacy. Here, we report the development and in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)-based scaffold, termed HA cryogel, with myeloid responsive degradation behavior. In mouse models of immune deficiency, we show that the infiltration of functional myeloid-lineage cells, specifically neutrophils, is essential to mediate HA cryogel degradation. Post-HSCT neutropenia in recipient mice delayed degradation of HA cryogels by up to 3 weeks. We harnessed the neutrophil-responsive degradation to sustain the release of granulocyte colony stimulating factor (G-CSF) from HA cryogels. Sustained release of G-CSF from HA cryogels enhanced post-HSCT neutrophil recovery, comparable to pegylated G-CSF, which, in turn, accelerated cryogel degradation. HA cryogels are a potential approach for enhancing neutrophils and concurrently assessing immune recovery in neutropenic hosts.

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Kerr, M., McBride, D., Johnson, W., Chumber, A., Najibi, A., Seo, B. R., Stafford, A., Scadden, D., Mooney, D., Shah, N.. 2022-01-23. Immune-responsive biodegradable scaffolds for enhancing neutrophil regeneration. https://doi.org/10.1101/2022.01.21.477275

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