Growing New Cartilage

The Technology:

The knee joint is very complex. It is composed of four bones, the ligaments that hold them together, the articular and meniscal cartilage that protects the ends, and the surrounding bursa.

The Hopkins cartilage regeneration technology encompasses a number of separate components to replace damaged cartilage in the knee or in other joints or locations. The technology provides a convenient and effective photopolymerization of a hydrogel that contains cells and growth factors necessary for the growth and integration of new cartilage in a damaged tissue.

While cartilage is often considered a simple tissue with chondrocytes sparsely distributed throughout an extracellular matrix of type II collagen and aggrecan, it is a complex, heterogenous tissue. On the cellular level chondrocytes are organized into superficial, proliferating, prehypertrophic and hypertrophic chondrocytes. These different types of chondrocytes have different cell morphology and gene expression. The extracellular matrix around the chondrocytes is also highly organized and changes depending on the where it is located. The cellular and extracellular matrix organization is controlled by mechanical and biological signals during development and after. There is a large wealth of molecular and cell biology that has been applied to cartilage tissue engineering. This technology uses hydrogels for tissue engineering.

Hydrogels encapsulate cells and absorb a large volume of liquid for nutrient and waste transport. The poly(ethylene oxide)-based photopolymerizing polymers can incorporate, through physical interactions or covalent bonds, extracellular matrix derived gels and proteins. The composite hydrogel has a synthetic portion where physical properties can be easily manipulated and a biological portion where cell response and tissue development can be manipulated.

Integration of a biomaterial with surrounding tissue is critical to long term survival and function. Particularly in the case of hard tissues such as cartilage in the musculoskeletal system, integration of an implant is difficult due to the dense nature of the extracellular matrix and large mechanical forces to which these tissues are often subjected. We have designed a method to direct covalent attachment of (meth)acrylated polymers to collagen proteins. Collagen is ubiquitous so that this method for implantation may be applied throughout. Covalent integration of hydrogel biomaterials significantly improves the mechanical integrity of the tissue-biomaterial interface in challenging applications such as cartilage.

Photopolymerization is used as a method to encapsulate cells for drug delivery and tissue engineering applications in our minimally invasive implantation systems. Most tissues in the body are complex, containing numerous cell types organized in specific extracellular matrix architecture. We have created multilayered photopolymerizing hydrogels in order to encapsulate numerous cell types or drug delivery vehicles. The tissue is comprised of layers of chondrocytes which contribute to the unique developmental and mechanical properties of the tissue. Furthermore, osteochondral implants, containing bone and cartilage are often used clinically to treat joint defects. Local factors released by the various cell types influence engineered tissue development and properties. Using the appropriate cell type, we have created both multilayered cartilage and osteochondral constructs to create engineered tissue with enhanced biochemical and functional properties.

A number of specialized hydrogels have also been optimized for specific cartilage regeneration applications. Proteoglycans are found throughout the body and serve numerous structural and functional roles. Chondroitin sulfate (CS) was modified to varying degrees with (meth)acrylate groups (CSMA) and polymerized to form a crosslinked hydrogel. Depending on the degree of modification, swelling, mechanical, and degradation properties of the CSMA hydrogels may be altered to fit a desired application. The CSMA gels are specifically degraded by chondroitinase and may be used as a diagnostic for the presence of chondroitinase, a degradative enzyme found in cartilage. Chondroitin sulfate is found naturally in other parts of the body including the intervertebral disc and may therefore be useful as a biomaterial in numerous applications.

The diagram below demonstrates the process of using the photopolymerizable hydrogel for cartilage repair. You can click on the diagram to see a larger version.

Creation of new cartilage will use controlled delivery of biological signals mentioned above in addition to physical signals provided by a scaffold to design anisotropic, organized cartilage tissue. In addition, chondrocytes with varying morphology and gene expression may be organized during the encapsulation process. Tissue engineered cartilage with an organized structure similar to native tissue will have functionality comparable to native tissue and may potentially integrate more easily into the heterogenous host tissue where it is implanted. This three-dimensionality is expected to increase the speed and efficacy of tissue regeneration.

Intellectual Property:

Multiple patent applications are currently pending and reviewable upon the execution of a confidentiality agreement

Elisseeff Receives Award

MIT's Technology Review magazine recently recognized Jennifer Elisseeff, assistant professor of biomedical engineering at Johns Hopkins, as one of the World's Top 100 Young Innovators in technology and business.

The Whitaker BME Institute
at Johns Hopkins University

With the nationally recognized Department of Biomedical Engineering as its core the Whitaker Biomedical Engineering Institute has been established as a vital link between the School of Medicine and the Whiting School of Engineering. The vision of the Institute is of an integrative research and education enterprise that will provide leadership in moving biomedical engineering to the forefront of biomedical science and practice. The Institute will be housed in Biomedical Engineering facilities in the School of Medicine and in Clark Hall, a new facility on the Homewood Campus.

The Department currently has 17 primary faculty members, approximately 100 graduate students, and over 450 undergraduates. Ten new faculty members will be added to the Institute over the next six years, thanks to a Whitaker Foundation Leadership Award. The undergraduate program leading to the bachelor of science in engineering in biomedical engineering is now the largest program on the Homewood campus.

Collaborators

Dr. Kam Leong, Ph.D.
Biomedical Engineering - The Johns Hopkins University
Synthetic and biological polymers applied to drug delivery, gene therapy, and tissue engineering.

Dr. Christopher Chen, M.D., Ph.D.
Biomedical Engineering - The Johns Hopkins University
Developing novel microfabrication and miniaturization tools for biological and medical research applications, understanding the mechanisms of tissue vascularization, the role of cell adhesion in cancer transformation, and the role of mechanical forces in cell function.

Dr. Kristi Anseth, Ph.D.
University of Colorado Biomaterials and Tissue Engineering
Developing strategies for encapsulating cells in polymer scaffolds for tissue engineering and selectively modifying these scaffolds to control cellular responses such as adhesion, proliferation, differentiation, and extracellular matrix production.