Synthetic Cell Culture Substrates

Nandanan Erathodiyil, Hongfang Lu, Susi Tan and Jackie Y. Ying

Stem cells are used for a variety of purposes, from understanding basic biology to generating differentiated cells, tissues and organs. Recent advancements in regenerative medicine and clinical applications of human stem cells have fueled the demand for large quantities of cells that need to be grown in the lab. In order to reduce batch to batch variation in lab-grown cells, researchers use a combination of synthetic substrates and media devoid of any human- or animal-derived components for their in vitro culture systems. This development has given rise to a multi-million dollar market for cell culture media. However, large-scale application of expensive materials, such as peptide-based substrates, remains prohibitive due to their cost. To fill this market gap, we are developing inexpensive fully synthetic coatings and microcarriers for the scalable expansion of stem cells. Under chemically defined conditions, our substrates can grow different types of human pluripotent stem cells for many cycles without any changes to their chromosome, while maintaining their cell type-specific properties in terms of self-renewal, marker expression and potency. We have also developed our new material into three-dimensional cell culture models that can support hepatocytes longer than conventional cell culture systems.

DNA Hydrogels

Yuwei Hu, Hongfang Lu, Susi Tan and Jackie Y. Ying

Composed of nucleic acid strands, DNA hydrogels are biocompatible, programmable and biodegradable. These properties allow them to mimic the dynamic nature of native extracellular matrix (ECM). The configurations of nucleic acid could be triggered by multiple external stimuli, such as pH, light, ion, enzyme, temperature and nucleic acid strands. This rich “tool-box” of switchable nucleic acid structures provides a versatile means to construct stimuli-responsive hydrogels that undergo reversible chemical and physical property changes, such as nucleic acid configuration, stiff ness, and permeability. Our lab is currently developing versatile, stimuli-responsive DNA hydrogels for cell differentiation and proliferation, cell-cell communication studies, as well as selective capture and release of cells. In addition, we are developing micro/nano DNA hydrogels with programmable chemical and physical properties for a variety of biological and medical applications, such as controlled delivery and release of drugs or food additives, sensing, self-healing, information storage and 2D/3D cell culture.

Chemically Defined Glues and Adhesives for Surgical Applications

Nandanan Erathodiyil, Hong Wu, Shu Jun Gao and Jackie Y. Ying

A major contributor to post-surgery complications is wound infection. This may result from poor wound management, including exposure to contaminants due to poor sealing of the wound. During the operation, surgeons may stitch the wounds close using sutures. However, sutures can be technically challenging, time-consuming and cause local tissue damage. Further, they may not provide an immediate waterproof seal for the wound. Another approach is to use surgical sealants, but existing sealants are often not adequately adhesive or mechanically strong enough. They are also usually cytotoxic and are not able to perform well in biological environments. The ideal surgical glue should meet three basic criteria, i.e. bond tissues strongly, be non-toxic and perform well in wet conditions. While there are many unmet medical needs that require better tissue adhesion, currently there are no clinically approved surgical glues that work well in wet and dynamic body environment. Our lab is developing chemically defined synthetic polymeric biomaterials to tackle these challenges.

Antifouling Materials for Wearable Implants

Nandanan Erathodiyil, Hong Wu, Shu Jun Gao and Jackie Y. Ying

The future of healthcare lies in wearable biomedical devices and implants. To ensure their effectiveness and safe application, it is critical for us to be able to control bio-interfacial phenomena or interactions between the implants and the physiological environment. The presence of a foreign body may trigger undesirable immune responses from the host, thus compromising the functioning of the devices or endangering the safety of users. Conventionally, anti-fouling polymers have been coated onto implantable surfaces to minimize the interaction of the designed surfaces with biomolecules, cells, bacteria and microorganisms. Our lab is currently designing new polymeric biomaterial coatings for next-generation wearable medical devices and implants. We have developed anew technique for synthesizing anti-fouling biomaterial coatings that will prevent protein and bacteria adsorption. Our technique is simpler, more versatile and less expensive than current approaches. We have used it to create novel nanostructured hydrogel materials of various compositions, architecture and surface chemistry, which have excellent anti-fouling performance and long-term durability in vivo. We are also designing chemically and structurally versatile anti-coagulant and omniphobic materials for this application.