# Age and sex differences in the immune response to synthetic materials

> **NIH NIH K99** · JOHNS HOPKINS UNIVERSITY · 2024 · $100,851

## Abstract

Project Summary
The WHO estimates that 1 in 6 people will be 60 years or older by 2030. A hallmark of aging is the
immunological changes that increase susceptibility of this population to inflammatory age-related diseases,
hinder response to infections and vaccines, and lower regenerative capacity. Synthetic biomaterials are used
in multiple ways including drug delivery, vaccines, prosthetics, and scaffolds in tissue engineering to promote
tissue regeneration. The immune system is the first responder to any injury and implants, and it directs the
foreign body reaction (FBR) to these materials—for synthetic materials it is often proinflammatory and leads to
scarring. This immune response is not only dependent on the material itself but both the tissue location and
underlying pathophysiology (patient’s demographic background and health) of the implant site. Thus, the
concept of “biocompatibility” is dependent on the current state of the host immune system which is significantly
influenced by the host’s age and sex. With an aging population there is a critical need to understand how the
age-specific proinflammatory skewed immune system alters the immune response to synthetic material
implants. The goal of this proposed work is to identify key biologic factors in the immune system and target
these with immunomodulatory synthetic materials for use in the aging population for tissue regeneration. The
overarching hypothesis is that the aged immune dysregulation towards an effector state compounds the
adverse reaction to synthetic materials. Using a previously described pro-fibrotic scaffold in a chronic non-
healing wound mouse model, combined with sequencing techniques, and phenotypic analysis, the experiments
in the K99 phase will elucidate the cell-cell communication networks in the aged FBR (Aim 1) as well as the
innate and adaptive immune shifts in response to synthetic materials over lifespan by sex (Aim 2). During the
independent research phase (R00), we will engineer multi-stage synthetic material systems to control the
dysregulated aged immune response in tissue engineering. Developing new immunomodulatory biomaterials is
critical to addressing the FBR to reduce unwanted implant related complications. Completion of this research
will provide training opportunities to master new technical approaches that will prepare the candidate to
become a primary investigator at a top-tier research institution studying the interface of the immune control of
wound healing and aging to synthetic biomaterial-based therapies.

## Key facts

- **NIH application ID:** 10829269
- **Project number:** 5K99AG081564-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Joscelyn Claraluz Mejias
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $100,851
- **Award type:** 5
- **Project period:** 2023-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829269

## Citation

> US National Institutes of Health, RePORTER application 10829269, Age and sex differences in the immune response to synthetic materials (5K99AG081564-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10829269. Licensed CC0.

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