Clinical tissue engineering for articular cartilage repair

Around 250,000 surgeries to repair articular cartilage1 are performed each year. Most of the damage surgeons are trying to fix begin as small lesions. Without treatment, small lesions become large holes that allow the bones of the joint to grind together. Sometimes these lesions are due to injury, but osteoarthritis is a large cause.

Current Cartilage Repair

If the lesion is small enough, the fix is just cleaning up the lesion by removing ragged tissue and waiting for healing to happen on its own. The second most common option is microfracture, where bleeding is induced from the bone to get new cells into the injured area. Both of these repairs have good short-term results, but begin to degrade in less than 5 years. Injecting autologous chondrocytes, cartilage cells from a different location in the same patient, has better long-term results, but only 30% heal normally.

The goal of tissue engineering is to improve on these outcomes by implanting a cartilage-like scaffold that can integrate with uninjured cartilage and, when it matures, be indistinguishable from healthy, natural articular cartilage. Brian J. Huang, et al., from the University of California Davis, reviewed 11 different tissue engineering solutions for articular cartilage repair that have been used clinically and improve on the standard therapy.

“The objective of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. … By understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineering cartilage products.” – Brian J. Huang, et al.2

Tissue Engineering in the Clinic

Ten of the 11 tissue engineering products reviewed follow the same paradigm and require two surgeries. The first surgery is to diagnose and describe a specific injury while gathering healthy cartilage cells, and the second is to implant the tissue engineered product to heal the injury.

Tissue engineering is defined as growing living tissue in a scaffold (provided for the cell or by the cell itself) outside of the patient until it is mature enough to help repair a defect. The cells gathered during the first surgery are grown in the lab, placed onto a scaffold where they are directed to grow into cartilage, then the second surgery implants the new tissue construct. The time between surgeries varies for each technique or product, but the wait is usually 4-8 weeks when natural polymers are used for the scaffold.

Eight of the products reviewed use natural polymers as the scaffold. This varies from decellularized animal tissue to collagen and hyaluronic acid. These natural materials are recognized as being versatile, biocompatible, and possessing inherent bioactivity that is beneficial to growing functional tissue. Each material has its own pros and cons, but most show the same short-term success as normal repair therapies while improving on the quality of the repaired tissue.

In two of the products, the cells made their own scaffold by exuding proteins that create an adhesive matrix. This method takes longer, up to 10 weeks between surgeries, but the final product is completely biological. The cells gathered during the first surgery are grown at very high density so that they adhere to each other and form their own scaffold with proteins. The conditions required to grow the cells in this method are more difficult to maintain than simply putting cells on a polymer scaffold, and it is a long wait until there are enough cells to produce this type of scaffold. However, this method seems to produce the most natural repair.

Conclusions and Comments

The paradigm described in this review of gathering a patient’s own cells, growing them into repair-tissue with a biocompatible scaffold, and then implanting that scaffold into an injury, will be the future of articular cartilage repair. Challenges remain, though, in improving the practicality of these treatments and in streamlining a process that currently takes about 15 years to get from lab to clinic.

The purpose of this review was to describe tissue engineering successes, so others could build upon them. Unfortunately, the path of building only on previously successful platforms is not the path of innovation. The idea that the ideal path will be found by building only on demonstrated successes is a hindrance to progression in tissue engineering in general. True innovation happens by sifting through reasons for failure as well as reasons for success. This is very hard to accomplish when the only thing reported in scientific journals is what worked, not what didn’t work.

Innovation within a lab using a specific technique is rare enough, more rare is innovation in a field as a whole. To move this field forward we need new ways of communicating what we have learned along the way.

  1. Articular cartilage covers the surface of bones in joints, lubricating movement so bones don’t destroy each other.
  2. Brian J. Huang, Jerry C. Hu, Kyriacos A. Athanasiou. “Cell-based tissue engineering strategies used in clinical repair of articular cartilage.” Biomaterials 98, 2016, 1-22.