Hu Zhang Publishes New Research on Osteochondral Regeneration

Dr. Hu Zhang, Professor in Bioprocessing at Keck Graduate Institute (KGI), has co-authored a groundbreaking research paper appearing in Applied Materials Today (Impact Factor 8.0) on the use of hydrogel for osteochondral (bone and cartilage) regeneration. The study specifically targets individuals with osteoarthritis, a condition that occurs when the cartilage covering certain joints wears down, resulting in pain around the knees, hands, and hips.

Historically it’s been thought that the only way to treat osteoarthritis is by managing the symptoms.

Zhang’s research proposes an approach that treats the issue at its source by repairing the damaged tissue. The way osteochondral regeneration works in this context is by combining hydrogel (a crosslinked network of synthetic polymers) with mesenchymal stem cells (MSCs), forming an aggregate.

The aggregate is then applied to the defective area of the joint, which regenerates bones and cartilage, enabling the joint to regain flexibility.

While other scientists are using hydrogel for tissue regeneration, what differentiates the work of Zhang and his team is their technique.

A common approach is to grow stem cells and then put them in the hydrogel and apply to the defective area.

“What we are doing is forming the aggregates first,” said Zhang. “The reason we’re doing it that way is because if you don’t form the aggregate first, the stem cells are quite small and can easily leak out from the defect site. So the retention rate is very, very low.”

The hydrogel provides a protective environment for the stem cells while at the same time inducing a synergistic effect that facilitates tissue regeneration. This occurs through the process of differentiation, as the MSCs change into bone and cartilage cells.

Another key component of this study is the use of a thermosensitive hydrogel, which allows for the stem cells to be delivered in the liquid formulation at room temperature, and the hydrogel solidifies at the defect site. This results in a more uniform, controlled delivery.

Zhang teaches Biotechnology and Emerging Therapeutics at KGI, and one of his ongoing research projects is smart systems for tissue regeneration. In addition to cartilage and osteochondral regeneration, he is also researching the use of cardiac progenitor stem cells to aid in heart repair.

Smart systems as applied to tissue regeneration uses scaffolding to create tissue that will respond favorably to the internal environment of the individual’s body. These smart systems can be used in the same way for more effective drug delivery, minimizing side effects by targeting only the disease cells.

“We try to utilize the kind of environment to promote the release of the drugs into the tumor cells, but they will not go into the healthy cells,” said Zhang.

Zhang also teaches the many components involved in bringing a product to market. He recently invited Dr. Danny Chou, an expert in protein formulation, to give two days of intensive lectures on industry practice for drug product formulation.

Additionally, Zhang leads the Team Design Project, where students work in teams to design a complete biomanufacturing plant capable of producing an API (active ingredient) or DP (drug product). Students must consider a manufacturable process for this API, whether to manufacture in-house or outsource, how many patients they can treat per year, and how they will build the plant, determining everything from square footage to costs.

These types of projects differentiate KGI from other pharmaceutical programs, providing students not only with hands-on training in the lab but also with the skills needed to address the economic and regulatory factors of the industry.

“They provide students with a broad overview of the project’s development and management so they can perceive the big picture,” said Zhang.

This holistic approach enables students to become well-rounded in their field and to comprehend how biochemistry, engineering, and economics work hand-in-hand. Such an approach is imperative in the rapidly evolving field of bioprocessing.

To learn more about KGI’s Master of Engineering in Biopharmaceutical Processing program, visit kgi.edu/meng.