# Optimization of engineered endplates to improve in vivo integration of atissue engineered intervertebral disc

> **NIH VA I21** · PHILADELPHIA VA MEDICAL CENTER · 2022 · —

## Abstract

Low back pain, most commonly caused by degeneration of the intervertebral disc,
places a significant social and economic burden on the general public, active duty
military and veterans alike. Current clinical treatments for disc degeneration are limited
in that they do not restore disc structure or function. To address this, our group has
developed a whole, tissue engineered intervertebral disc composite (eDAPS) composed
of engineered annulus fibrosus, nucleus pulposus and endplate regions. The endplate
component, composed of an acellular porous polymer foam, is a critical aspect of the
design that forms the interface between the engineered disc and native vertebral bone,
but has yet to be optimized to promote the accelerated development of a vascularized,
boney interface. The purpose of this study is to generate design modifications to the
endplate region of the eDAPS that will accelerate integration following in vivo
implantation. We will achieve this translational goal through two Aims: Aim 1: Modify the
composition and geometry of the endplate region of the eDAPS to enhance
osteogenesis and neovascularization. In this Aim, poly(ε-caprolactone) (PCL) endplates
will be fabricated via a salt-leaching procedure with various design modifications to
promote osteogenesis and neovascularization. PDMS molds will first be used to create
macroscopic channel geometries within the endplates. Endplates will be further modified
via hydroxyapatite deposition, and the incorporation of microspheres containing vascular
endothelial growth factor (VEGF). The potential for mesenchymal stem cell osteogenesis
on the hydroxyapatite modified scaffolds will be established in vitro, via the alkaline
phosphatase assay, qPCR analysis of osteogenic genes, and histology. The bioactivity
of the VEGF released from the microsphere containing scaffolds will also be assessed in
vitro using the tube formation assay. Aim 2: Determine the effect of optimized endplate
design on the in vivo integration and nutrition of a whole tissue engineered disc
construct. In this Aim, optimized endplates will be utilized in eDAPS to be implanted in
vivo in the rabbit lumbar spine for 10 or 20 weeks. New bone and vascular formation in
the endplates following in vivo implantation will be assessed via calcein and alizarin
labelling and microFil enhanced µCT, respectively. Small molecule trans-endplate
diffusion into the engineered disc implants will be assessed via post-contrast enhanced
MRI. Integration strength of the eDAPS with the native vertebral bodies will be assessed
via tension, compression and torsional mechanical testing at physiologic loads. Animal
functional rehabilitation following eDAPS implantation will be assessed via activity
monitoring using the Motionwatch-8R, and ground reaction force mapping during
ambulation using a Tekscan system. The proposed work will advance the state-of-the art
in the field of intervertebral disc tissue-engineering, and provide insights that will speed
t...

## Key facts

- **NIH application ID:** 10540676
- **Project number:** 5I21RX003289-03
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** SARAH E GULLBRAND
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-12-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10540676

## Citation

> US National Institutes of Health, RePORTER application 10540676, Optimization of engineered endplates to improve in vivo integration of atissue engineered intervertebral disc (5I21RX003289-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10540676. Licensed CC0.

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