Creating a More Natural Engineered Cartilage

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Creating a More Natural Engineered Cartilage

Natural human cartilage has a simple structure with no blood or nerve supply. These characteristics contribute to its inability to repair itself when damaged. These same characteristics also make it a prime candidate for cell-based tissue engineering efforts.

What Problem Was Studied?
Osteoarthritis and rheumatoid arthritis are just two of a number of diseases that result in damage and destruction of cartilage. Scientists are working hard to devise artificial cartilage that might be useful in replacing diseased cartilage. Natural cartilage is organized into three distinct layers, each of which contains slightly different types of chondrocytes. The superficial zone contains flattened chondrocytes and collagen fibrils aligned with the joint surfaces. The transitional zone contains more rounded chondrocytes and randomly arranged collagen fibrils. The deep zone contains large, spherical chondrocytes embedded in a dense structural matrix and thick collagen fibrils. To date, most attempts to grow cartilage have involved seeding a uniform framework with identical chondrocytes, creating a structurally consistent tissue. Researchers from Johns Hopkins University in Baltimore and Seoul National University in Korea have been working on engineering cartilage that is organized into more natural, stratified layers containing the different subtypes of cartilage cells.

Anatomy Basics

Cartilage: A dense connective tissue composed of cells called chondrocytes, a firm gel-like substance called the matrix, and collagen and elastin fibers.

Chondrocytes: Cells that produce and maintain cartilage.

Collagen fibrils: Very thin fibers of the long-structural proteins in connective tissue.

Glycosaminoglycan: Long molecules that form an important component of connective tissue.

Collagen: The main protein component of cartilage.

What Was Done in the Study?
Principal investigator and Arthritis Foundation grant recipient, Jennifer H. Elisseeff, PhD, used special scaffolds and a technique developed by her team called photopolymerization to create engineered cartilage containing two layers. Cells from the superficial zone of calf cartilage were processed and poured onto a polymer framework. By exposing this polymer to ultraviolet light for a specific amount of time, the layer was “soft set.” Next, cells from the deep zone of calf cartilage were processed and poured onto a polymer scaffold over the first layer. This layer was then exposed to ultraviolet light and set.

Now that the research team created a bilayer tissue complete with different types of chondrocytes in the layers, they tested the characteristics of the tissue to see if it more closely resembled natural cartilage than the homogeneous engineered tissue.

What Were the Study Results?
The layered tissue allowed chemical signaling between the cells of the different zones, a feature important for proper cartilage growth and development. The cells of the layers maintained distinct traits, which led to a stratified cartilage with some features of natural cartilage. Specifically, the deep layer produced two to three times as much glycosaminoglycan and collagen than the superficial layer, but natural deep-zone cartilage produces 10 times as much. The bilayered tissue also demonstrated superior mechanical properties to homogeneous engineered tissues.

What Does This Mean for People With Arthritis?
Being able to create a more naturally organized, layered cartilage is important for advancing the technology and attaining the successful transplantation of replacement cartilage in the joints of people with arthritis. Elisseeff envisions that multilayered tissue could be created in areas of damaged cartilage by injecting layers of polymer-cell mixtures into the joint and curing them with light using the photopolymerization technique.