A Novel Glycosaminoglycan Mimetic Scaffold for Cartilage Repair

Project Summary
With the limited healing capability of articular cartilage, clinical intervention is necessary to prevent
further articular cartilage damage and early onset of degenerative osteoarthritis. Current surgical
procedures result in inadequate repair suffering from poor integration with surrounding hyaline cartilage
and the formation of fibrocartilage instead of normal hyaline cartilage. The most frequently used reparative
treatment for small symptomatic lesions of articular cartilage of the knee is microfracturing, where multiple
holes are made in the subchondral bone allowing stem cells from the bone marrow to migrate to the joint
surface and facilitate repair. However, in the long-term, this method does not result in the replacement of
normal hyaline cartilage. The approach described here is to combine the surgical treatment of
microfracturing, which will provide endogenous cells capable of chondrogenesis to the defect site, with a
novel scaffold that mimics the cartilage extracellular matrix during development to promote
chondrogenesis and cartilage tissue formation. During cartilage development, the major matrix
components are collagens and proteoglycans, wherein the predominant glycosaminoglycans (GAGs) in
the proteoglycans are chondroitin-6-sulfate and heparin sulfate. The pattern and degree of sulfation in
these and other GAGs play an integral role in providing the necessary functionality/bioactivity for growth
factor interactions in cartilage development. Typical synthetic biomaterials lack functional sites that would
enable this interaction. This study will investigate a semi-synthetic derivative of cellulose, which is one
of the most abundant natural materials, for cartilage repair. Sodium cellulose sulfate (NaCS), which is
water soluble and mimics the structure of GAG, will be fabricated into a scaffold and combined with
microfracturing as a novel strategy for cartilage repair. NaCS is a linear polysaccharide that can be
synthesized with varying degrees of sulfation for improved bioactivity over native GAGs. In our studies to
date, fully sulfated NaCS has shown promise in promoting chondrogenesis and accelerating the repair
of osteochondral defects. We hypothesize that NaCS will impart functional qualities that are similar to
GAGs, direct chondrogenesis and cartilage tissue formation. Aim 1 will fabricate and characterize NaCS
constructs and investigate bone marrow derived mesenchymal stem cell (MSC) chondrogenesis in vitro.
Aim 2 will evaluate cartilage tissue formation and integration in vivo. The goal of this aim is to
evaluate cartilage tissue formation and integration with surrounding host cartilage in a rabbit defect
model. Aim 3 will investigate NaCS constructs in a clinically relevant, critically-sized cartilage defect
model. This study proposes a novel GAG-mimetic strategy where NaCS containing scaffolds can be
combined with microfracturing as an effective and translatable strategy for treating cartilage lesions.

Grant Number: 5R01AR077056-05
NIH Institute/Center: NIH
Principal Investigator: Treena Arinzeh