AO Research Institute Davos (ARI), Clavadelerstrasse 8, 7270 Davos, Switzerland
Date, time: January 7, 13:00 - 14:00 in the Prof. Arkadiusz Piekara Auditorium, Collegium Physicum
"Immuno-active self-assembling peptides for spatiotemporal regulation of chronic inflammation (under standard and simulated micro-gravity)"
Abstract: Numerous chronic, inflammation-driven conditions, such as tendinopathy, involve prolonged immune imbalance, with macrophages (MΦs) and their cross-talk with stromal cells playing a central role in dictating healing.1 Biomaterial-based strategies can guide MΦ responses toward regeneration, particularly in severe injuries. Inspired by nature’s homochirality, self-assembling peptides (SAPs) provide a minimalistic platform for designing functional biomaterials. Here, we present an extended family of tyrosine-modified β-sheet-forming SAPs.2 By varying hydrophobic/hydrophilic residues and tyrosine placement, as well as choosing the overall chirality state (L- versus D-), we were able to tune their physicochemical properties and interactions with MΦs. These SAPs ImmunoBioInks were comprehensively characterized using physicochemical and molecular dynamics analyses, and their effects on MΦ polarization were evaluated in THP-1 and donor-derived PBMC-derived cells through molecular and cellular assays. Additionally, we compared the behavior of SAPs used for modulation of immune system cells, both under standard gravity and simulated microgravity (µG), hence named Space ImmunoBioinks, with the goal of providing novel tools for tissue regeneration studies in space.3 Our (Space) ImmunoBioinks are injectable and structuring SAP hydrogels with a wide range of physical properties, inducing a spectrum of biological responses. Among L-variants, we identified two negatively charged key modulators, EF8, which induced an anti-inflammatory M2 response (CD105, CD163, CD206 upregulation, IL-10 secretion), and YEF8, which favoured an M1-like phenotype (increased HLA-DR expression and TNF-α secretion). 2 Their cellular immunomodulatory responses were more pronounced as compared to existing hyaluronic acid-based therapies. 4 On the other hand, positively charged SAPs KYF8 and KYF8K revealed distinct immunomodulatory effects, with KYF8K exhibiting a unique Th1-promoting phenotype characterized by an increased IL-2, IP-10, MCP-1, TNF-α and IFN-γ, secretion. Homochiral D-variants of EF8 and YEF8 confirmed immunomodulatory induction of polarization, albeit with lower response as compared to L-variants. Our work highlights the pivotal role of SAP chemistry and chirality in MΦ modulation and introduces new strategies for spatiotemporal control of musculoskeletal inflammation, ultimately providing previously unseen therapeutic opportunities in regenerative medicine, both on earth and in conditioned space environments.
References:
1. J. Lee, et al., Adv Healthc Mater, 2019, 8, e1801106.
2. J. K. Wychowaniec, et al., ACS Applied Materials & Interfaces, 2025, 17, 27740-27758.
3. H. Stenuit, et al., Cell Biomaterials, 2025, 1.
4. J. K. Wychowaniec, et al., Biomaterials Advances, 2025, 169, 214166.
Acknowledgements:
This work was supported by the AO Foundation, EU H2020-MSCA-IF-2019 (no.893099-ImmunoBioInks), LEADING HOUSE MENA Research Partnership (RPG-2022-38) and Consolidation (COG-2023-35) grants