# Modifying High Modulus Hydrogels for Cell Delivery: Intervertebral Disc Repair with Genipin-Crosslinked Fibrin

> **NIH NIH F31** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $8,623

## Abstract

PROJECT SUMMARY
Back and neck pain are leading causes of global disability, which account for over $135 billion in healthcare
spending. Disabling back pain caused by herniation of the intervertebral disc (IVD) can be alleviated by
discectomy, the surgical standard of care that removes herniated IVD tissue. While effective, discectomy does
not repair annulus fibrosus (AF) defects caused by the herniation, which can lead to accelerated IVD
degeneration, reherniation and recurrent pain. Cell-seeded, adhesive hydrogels are a promising strategy to
prevent these complications because they can immediately seal AF defects and deliver cells for long-term
healing. Engineering such hydrogels for IVD cell delivery is challenging because soft biomaterials typically used
for cell delivery risk herniating in the IVD injury space. On the contrary, high-modulus biomaterials designed to
bear high-magnitude spine loads can hinder the healing capacity of encapsulated cells. The overall goal of this
research proposal is to uniquely integrate principles of cellular microencapsulation, degradable microbeads
(MBs) and high-modulus biomaterials to engineer next-generation biomaterials that promote IVD regeneration
and functional repair. Aim 1 will assess the protective capacity and degradation kinetics of oxidized alginate
(OxAlg) MBs. Aim 2 will characterize the effects of genipin-crosslinked fibrin (FibGen)-OxAlg construct
macroporosity on AF cell phenotype and construct biomechanics. Aim 3 will evaluate the biological and
biomechanical repair responses of FibGen-OxAlg. Our global hypotheses are that OxAlg MBs will protect
AF cells from FibGen hydrogel crosslinking then degrade (Aim 1). Resultant macroporous FibGen-OxAlg
constructs will promote AF cell proliferation and ECM synthesis, leading to enhanced construct
biomechanics (Aim 2). This cell delivery strategy will promote biological and biomechanical repair in ex
vivo IVD organ culture (Aim 3). This work is significant because it develops an easily translatable tissue
engineering strategy to address the critical clinical challenges associated with AF defects; this approach may be
broadly applicable to other musculoskeletal tissues that exhibit limited healing and experience high mechanical
demands, which strongly aligns with the mission of NIAMS. This proposal is highly innovative because no
strategies that repair and regenerate AF defects exist, few published studies use cell-laden MBs as porogens in
templated hydrogel constructs, and none use such constructs in IVD repair. Validating the efficacy of this
biomaterial strategy in a loaded, large animal IVD organ culture system is innovative and significant because
there are few published studies using such a culture system and testing in this manner will accelerate clinical
translation. Completion of the proposed aims will provide the candidate with rigorous multidisciplinary training in
biomaterial synthesis, cell microencapsulation, biomechanical testing and IVD ...

## Key facts

- **NIH application ID:** 10397389
- **Project number:** 5F31AR077385-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Christopher James Panebianco
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $8,623
- **Award type:** 5
- **Project period:** 2021-04-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397389

## Citation

> US National Institutes of Health, RePORTER application 10397389, Modifying High Modulus Hydrogels for Cell Delivery: Intervertebral Disc Repair with Genipin-Crosslinked Fibrin (5F31AR077385-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10397389. Licensed CC0.

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