# Controlled-release Microbeads to Replace Growth Factors in Fetal Bovine Serum

> **NIH NIH R41** · STEMCULTURES, LLC · 2021 · $225,501

## Abstract

Project Summary / Abstract:
Fetal bovine serum (FBS) contains a variety growth factors (GFs) and GF-stabilizing agents that have a potent
influence on cell behavior. Lot-to-lot variability of FBS, however, results in fluctuation of initial GF levels. These
fluctuations are further complicated by time-dependent decay at rates unique to each GF, resulting in changing
GF ratios over time. These three FBS characteristics (variable initial GF levels, time-dependent decay, and
varying GF ratios over time) make it difficult to know actual GF levels maintained during the culture period.
Knowledge and control of GF levels, however, is needed to systematically formulate media to effectively replace
the GFs provided by FBS We propose to manufacture controlled-release microspheres that maintain stable,
defined GF levels to facilitate the development of an FBS-free medium. Replacing FBS GFs is a meaningful step
toward addressing the FOA PA-18-816 goals of: ‘Better Defining Growth Medium to Improve Reproducibility
of Cell Culture’ and ‘supporting technologies and products to expedite development of better serum
substitutes’.
 A challenge to originating serum-free protocols is the rapid degradation of soluble GFs that are typically
added to media at the time of use. StemCultures, LLC manufactures controlled-release poly lactic-co-glycolic
acid (PLGA) microbeads that slowly release GFs to produce defined and stable GF levels in culture media. This
flexible PLGA microbead platform will be used to generate a series of ‘CultureBeads’ that release key FBS GFs
to maintain a stable media level over several days. Four FBS GFs will provide proof-of-concept for the controlled-
release strategy. The initial four FBS GFs were selected based on: 1) presence in FBS, 2) lability and 3)
bioactivity. Each CultureBead replaces one FBS GF, allowing CultureBeads to be combined to provide a stable
GF mixture. The second aim advances automated microfluidic manufacturing to facilitate cost-effective current
Good Manufacturing Process (cGMP) compliant CultureBeads production. The initial CultureBeads tool kit can
be utilized for specific cell types dependent on the selected GFs, including retinal pigment epithelium (RPE) cells,
certain mesenchymal stem cells and pluripotent stem cells where there is broad demand. CultureBeads
manufacture of RPE has immediate application for an FDA-approved, NIH-sponsored clinical trial. In a future
Phase 2 STTR application, the CultureBeads series will be expanded using multiplex analysis to identify
additional factors to more completely replace FBS.

## Key facts

- **NIH application ID:** 10254493
- **Project number:** 1R41GM142345-01
- **Recipient organization:** STEMCULTURES, LLC
- **Principal Investigator:** Jeffrey H Stern
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,501
- **Award type:** 1
- **Project period:** 2021-09-20 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254493

## Citation

> US National Institutes of Health, RePORTER application 10254493, Controlled-release Microbeads to Replace Growth Factors in Fetal Bovine Serum (1R41GM142345-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10254493. Licensed CC0.

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