# Cell membrane-coated macroporous scaffolds for enhancing bone regeneration in aging

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $615,387

## Abstract

Cell membrane (CellMem) coating has emerged as a biomimetic strategy to modify polymeric
nanoparticles for drug delivery applications. Compared to using individual ligands, CellMem
coating has unique advantages in biomimicry by borrowing the entire ligand repertoire contained
in the cell membrane. Our lab has recently explored combining CellMem coating with
macroporous scaffolds for enhancing tissue regeneration via immunomodulation. We
demonstrated that coating of macroporous gelatin microribbon (µRB) scaffolds with CellMem
from primed mesenchymal stem cells (pMSCs) induced regenerative immune response and
enhanced bone healing in a mouse disease model. While our previous study demonstrates the
promise of CellMem-coated µRB scaffolds for regeneration, it was limited to using cells from
young donors and in a young disease model, yet patients needing therapies are mostly aged
population. Aging is known to be associated with excessive inflammation and delayed healing.
As such, the goal of this proposal is to determine optimal CellMem coating for enhancing bone
regeneration in aging via targeting immunomodulation and to elucidate how varying CellMem
coating modulates MSC/immune cell crosstalk. We propose to use allogeneic CellMem isolated
from young donors due to their more abundant supply and more potent functionality than
CellMem from aged donors. We choose CellMem from pMSCs and M1 Mφ due to their
immunomodulatory functions and ability to scavenge inflammatory cytokines, respectively. We
hypothesize that varying the ratio of MSC/ Mφ CellMem coating will modulate Mφ polarization
and MSC osteogenesis in vitro. We further hypothesize that cells from young and aged donors
would require a different optimal ratio of CellMem coating. To test these hypotheses, we will
assess the effects of varying ratios of CellMem coating on individual cell types and
MSC/immune cell crosstalk in vitro using cells from young and aged donors. We devised a tri-
culture model (MSC/ Mφ/T cells) to better mimic the complex cellular crosstalk in vivo. Lead
formulations that result in robust bone formation in the tri-culture model will be validated in vivo
using young and aged mouse critical-sized bone defect models. Our team has a long track
record of productive collaborations and this project will integrate our complementary expertise in
biomaterials, immunology, bone biology, aged animal models, tissue engineering, mass
cytometry, and single-cell sequencing. This project will pioneer the translation of CellMem-
coated scaffolds for enhanced regeneration in aging and elucidate the underlying mechanisms
through the use of a tri-culture model and high-dimensional assays.

## Key facts

- **NIH application ID:** 10980904
- **Project number:** 1R01AI180049-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Fan Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $615,387
- **Award type:** 1
- **Project period:** 2024-06-11 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980904

## Citation

> US National Institutes of Health, RePORTER application 10980904, Cell membrane-coated macroporous scaffolds for enhancing bone regeneration in aging (1R01AI180049-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10980904. Licensed CC0.

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