Instantaneous and Robust Hydrogel Adhesion via Chitosan Films: A Novel Approach for Biomedical Applications


Hydrogels are widely used in biomedical applications due to their biocompatibility and physical properties that closely mimic natural tissue. Traditional methods for bonding hydrogels involve either covalent bonding or liquid-based adhesion strategies, each with inherent limitations. Covalent bonding, while strong, typically requires complex chemical reactions, often involving toxic substances and can adversely affect the biocompatibility of the hydrogels. Liquid-based methods, although safer, generally suffer from slow adhesion speeds, limiting their practicality in clinical situations where rapid action is needed.

A new study published in the Proceeding of the National Academy of Science USA and conducted by Dr. Benjamin Freedman, Juan Cintron Cruz, Phoebe Kwon, Matthew Lee, Haley Jeffers, Daniel Kent, Dr. Kyle Wu, James Weaver, and led by Professor David Mooney from the Wyss Institute for Biologically Inspired Engineering, Harvard University, the researchers developed an innovative method for achieving rapid, robust adhesion between hydrogels using chitosan films. This development holds considerable potential to revolutionize applications in medicine and surgery, where fast and reliable adhesion is critical. The research team’s approach centers on the use of chitosan, a naturally derived polymer known for its biocompatibility and bioactivity in various medical applications. By fabricating thin films from chitosan and applying them to hydrogel surfaces, the team discovered that these films could rapidly induce adhesion through a combination of non-covalent bonds, such as hydrogen bonds and Van der Waals forces, and physical entanglements at the interface. The significance of this approach lies in its simplicity and effectiveness. Unlike previous methods that required the hydrogels to be pre-treated or modified chemically, the chitosan films work effectively under physiological conditions and can be applied instantly. This feature is particularly advantageous in surgical environments, where time and safety are of the essence.

The mechanism of adhesion facilitated by the chitosan films is multifaceted. At a physiological pH, chitosan becomes protonated, enhancing its ability to form hydrogen bonds with the hydrogel surfaces. This interaction is critical because it allows for the formation of a strong, interconnected network between the chitosan and hydrogel polymers. Additionally, the physical entanglement of polymer chains at the interface further strengthens the bond, providing structural integrity and robustness that is crucial for many medical applications.

The team conducted a series of experiments to characterize the adhesion properties of the chitosan films. They measured the adhesive energy and observed that it significantly exceeded that of traditional adhesion methods, reaching values greater than 3,000 J/m^2. This high level of adhesion energy not only demonstrates the effectiveness of the chitosan films but also highlights their potential to provide a durable bond under the dynamic and often challenging conditions of the human body.

The practical applications of this technology are vast. In surgical settings, the ability to quickly and effectively bond hydrogels can be utilized in tissue engineering, wound closure, and as sealants during surgical procedures. For example, in vascular surgery, rapid hydrogel adhesion can help achieve immediate hemostasis, significantly reducing surgical time and improving patient outcomes. Another promising application is in the development of wearable or implantable medical devices. Hydrogels, due to their soft and flexible nature, are ideal for interfacing with bodily tissues. The chitosan film technology could facilitate the integration of these devices with human tissue, ensuring secure attachment and enhancing the functionality of the devices. While the study’s findings are promising, further research is needed to fully understand the long-term stability and biocompatibility of the chitosan-hydrogel bonds in vivo. Furthermore, the authors tested on various tissues like bowel, tendon, and nerves, proving its effectiveness in insulating tissues during surgery to prevent fibrotic adhesions—a significant yet unmet clinical need. Future studies should also explore the scalability of this technology, including the development of automated systems for applying chitosan films in a clinical setting. Moreover, exploring the environmental factors that might affect the adhesion process, such as humidity and temperature, would provide deeper insights into the versatility and robustness of this adhesion strategy under different conditions.

The research by Professor Mooney and his team created a powerful new tool for medical adhesion applications. This technology has the potential to improve surgical outcomes, enhance the functionality of medical devices, and lead to new innovations in tissue engineering. As this technology advances, it could become a new standard for medical adhesion, benefiting patients and healthcare providers alike by providing safer, faster, and more reliable treatment options.

Instantaneous and Robust Hydrogel Adhesion via Chitosan Films: A Novel Approach for Biomedical Applications - Medicine Innovates
This illustration highlights how two hydrogels (shown in blue) can be bonded in different ways by thin chitosan films (shown in orange). The bonds that form are extraordinarily strong and can resist high tensions. [Image courtesy of Peter Allen, Ryan Allen, and James C. Weaver]

About the author

David J. Mooney, Ph.D.

Founding Core Faculty & Lead, Immuno-Materials
Wyss Institute at Harvard University
Robert P. Pinkas Family Professor of Bioengineering
Harvard John A. Paulson School of Engineering and Applied Sciences

Dave is studying the mechanisms that enable cells to receive and react to chemical and mechanical signals, such as cell adhesion molecules and cyclic strains. These signals carry information that tells cells to alter their behavior by changing their level of proliferation or area of specialization. Sometimes the message being sent is to promote tissue growth: sometimes it’s to attack diseased cells. Dave is working to understand the conditions under which these signals develop: how much of a particular mechanical or chemical factor is needed, at what location, and at what time. The results of these studies will help him design new materials and devices that mimic the conditions needed to send specific orders to the body’s cells. His current projects focus on therapeutic angiogenesis, regeneration of musculoskeletal tissues, and cancer therapies. In 2009, Dave’s team developed the first vaccine ever to eliminate melanoma tumors in mice. It is a tiny bioengineered disc filled with tumor-specific antigens that can be inserted under the skin where it activates the immune system to destroy tumor cells. While typical tissue engineering involves growing cells outside the body, his novel approach reprograms cells that are already in the body.

Dave is the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. He plays an active role in the major biomedical and chemical engineering professional societies, serves as an editorial advisor to several journals and publishers, organizes and chairs leading conferences and symposia, and participates on several industry advisory boards.

About the author

Daniel O. Kent, M.D.


Dan is a resident physician in General Surgery who joined the Wyss Institute during his research elective as a Clinical Fellow working on surgical biotechnology. Dan grew up in California and graduated from UCLA with a degree in International Development Studies, focusing on Global Health. After college, he began to develop an interest in surgical technology while working at a medical device start-up in Silicon Valley. He went on to receive his M.D. at Albany Medical College and subsequently began his General Surgery residency at the Beth Israel Deaconess Medical Center. His current focus is developing and testing surgical micro-robotic prototypes with the Wood Lab that are designed to enhance the capabilities of minimally invasive surgery at the millimeter scale. Additionally, he is participating in pre-clinical testing of other technology platforms that will serve as the basis for new surgical devices and materials. Dan is also interested in exploring how the creative problem-solving process inherent to innovation can be applied to the core curriculum of surgical training.


Freedman BR, Cintron Cruz JA, Kwon P, Lee M, Jeffers HM, Kent D, Wu KC, Weaver JC, Mooney DJ. Instant tough adhesion of polymer networks. Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2304643121. doi: 10.1073/pnas.2304643121.

Go To Proc Natl Acad Sci U S A.