**Acknowledgements**

*Hydrogels - Smart Materials for Biomedical Applications*

*Thixotropic HA hydrogels. (A) Hyaluronic acid and gelatin thixotropic hydrogel, formed using complexing with tetraorthosilicate (TEOS). (B) A depiction of a thixotropic loop mechanical test and (C) the HA-gelatin thixotropic hydrogel under such a test, indicating thixotropic characteristics. (D) A stress sweep and recovery* 

acrylate crosslinkers to stiffen the gel [78, 79]; multistep spontaneous and lightinitiated crosslinking to spatio-temporally regulate crosslinking (**Figure 6**, **Table 7** [80, 81]); and inclusion of tetraorthosilicate to render HyStem thixotropic (allowing

In summary, HyStem's strength is in its clinical roots, its protein and cell compatibility, and its flexibility to enable optimized drug and cell delivery. These attributes make HyStem well-suited for present applications such as local delivery of protein and autologous cells as well as future applications are also such as organoid culture for better drug discovery and development as well as bioprinting of tissue and organs. in the longer term, we envision HyStem to be a platform for using these new technologies to develop the next generation of made-to-order therapies and tissues for an increasing tissue and organ starved human community, whether it be an individual requiring an organ transplant due to disease, a tissue transplant due to

We also envision HyStem eventually becoming a standard building block for a wide variety of future therapies so that it is clinically available for a physician as an

extrusion due to reversible liquefaction of the hydrogel (**Figure 7**)).

injury, or the multiple needs of the wounded warrior.

**112**

**Figure 7.**

*demonstrating thixotropy.*

**6. Conclusion**

We thank Michael Onorato, Dr. Jennifer Bahr-Davidson and Dr. Francois Binette for critical reading of the manuscript as well as Brooke Lohman and Michael Onorato for sharing unpublished data. We also dedicate this book chapter to our mentors and friends Drs. Glenn Prestwich and Bill Tew who breathed life into the HyStem platform from invention to commercialization; without their vision and energy, the HyStem platform would have never happened.

## **Conflict of interest**

Dr. Zarembinski is an employee of and owns stock options in BioTime, Inc.
