# Enhanced Soft Tissue-to-Bone Healing via Treatment with Novel Growth Factor NELL-1: Targeted Delivery and Biomimetic Scaffolds

> **NIH VA IK2** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2022 · —

## Abstract

I am an Orthopaedic Sports Medicine specialist pursuing a career as a clinician-scientist
focusing on the biology of soft tissue healing to bone. The comprehensive training plan
described in this proposal will uniquely position me as a surgeon-scientist to i) investigate the
biology of soft-tissue-to-bone healing, ii) characterize novel approaches for growth factor
delivery and scaffold design, iii) perform preclinical assessments of potential therapies and,
ultimately, iv) design and operate appropriately powered clinical trials aimed at improving the
treatment of soft tissue musculoskeletal injuries.
There are 32 million musculoskeletal injuries in the United States annually of which 45% involve
tendons or ligaments. Complete tendon and ligament separation injuries do not heal back to
their bony attachments without surgical intervention and, thus, are often treated with surgical
procedures including rotator cuff tendon repairs and anterior cruciate ligament reconstructions.
There are more than 5.7 million people with a rotator cuff tendon tear in the US alone and this
number is increasing as our population ages. In addition, there are more than 200,000 ACL
injuries in the US each year; the incidence of these injuries in the military population is ten times
higher than that of the civilian population. Normal tendon and ligament insertions to bone are
comprised of a complex tissue structure that effectively transmits the interactions between
dynamic muscle tissues and the rigid skeleton. Unfortunately, surgically repaired tendon tears
and ligament reconstruction procedures characteristically “heal” with an abnormal tissue
architecture that results in inferior biomechanical properties resulting in high failure rates. In this
proposal we aim to stimulate local progenitor cells to repair the enthesis via a novel approach by
delivering bisphosphonate-targeted growth factors to the bony site of the ruptured enthesis
coupled with the insertion of a uniquely-designed biomimetic scaffold embedded with those
factors.
The CDA award would provide me the opportunity to turn potential into results. In order to
accomplish the aims of this proposal we have assembled an internationally-recognized
mentoring team to provide me with the technical training required for this research. In parallel
with my mentored technical training, instruction in career development, drug discovery, data
analysis and translational aspects relevant to my research goals will be provided via the UCLA
CTSA-sponsored Training Program in Translational Science modules and supplemental
graduate school course work. With guaranteed protected time, institutional financial support
from my Department and 500 square feet of independent laboratory space and with
transdisciplinary, cross-specialty guidance provided by my mentorship committee, my scientific
advisory panel and my team of collaborators to assist in my development into an independent
translational scientist, The ultimate goal is to allo...

## Key facts

- **NIH application ID:** 10456093
- **Project number:** 5IK2BX005199-03
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** THOMAS John KREMEN
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456093

## Citation

> US National Institutes of Health, RePORTER application 10456093, Enhanced Soft Tissue-to-Bone Healing via Treatment with Novel Growth Factor NELL-1: Targeted Delivery and Biomimetic Scaffolds (5IK2BX005199-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456093. Licensed CC0.

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