2019-866 METHODS FOR IMPROVING THE TISSUE SEALING PROPERTIES OF HYDROGELS AND THE USE THEREOF

UCLA researchers in the Department of Bioengineering have optimized the sealing properties of naturally derived biopolymers, without altering their other attractive abilities like biodegradation.

 

BACKGROUND:

A significant number of emergency room cases consist of wound-related injuries. While the body is particularly adapted to treat various types of damages to tissue, certain wounds may be too severe for the body to handle. Further exacerbating this issue lie certain underlying health complications like diabetes, which may further limit the body’s ability to close wounds. Due to this unmet healthcare need, much research interest has been invested into tissue sealants. Unfortunately, many initially successful methods made use of certain materials that would need to be removed once the wound has been closed. While this may not pose an issue for epidermal wound closure, damages that are closer to bodily organs would need a separate surgical extraction process. Instead, much attention has been given to the field of naturally derived biopolymers that can be readily degraded by the body once the wound has been closed. Despite many of their advantages, biopolymers typically lack mechanical robustness rendering them weak sealants. Therefore, a need remains to make use of the various advantages of naturally derived biopolymers while also solving issues relating to their sealing capabilities. 

 

INNOVATION:

UCLA researchers in the Department of Bioengineering have optimized the sealing properties of naturally derived biopolymers, without altering their other attractive abilities like biodegradation.  The mechanical robustness of the biopolymer is enhanced through the addition of a small concentration of synthetic, biocompatible polymer. Through a series of studies, the researchers found an optimal concentration of synthetic polymer that could be added before leading to detrimental sealing strength. The engineered biopolymer can effectively close tissue while also providing an adhesive barrier against fluid leakage. Comparative to commercially available sealants, the engineered biopolymer can outperform while also offering attractive qualities like cost-effective fabrication and biodegradation. Aside from use as a tissue sealant, the engineered biopolymer may have further uses in the fields of drug delivery, hygiene, paint, biomedicine (e.g., peptide/protein stabilization, immunomodulating implants), and hydrogel probes. The researchers speculate that this engineered biopolymer will serve as the first in the new emergence of highly adhesive biodegradable hydrogels for advanced biomedical applications worldwide. 

 

POTENTIAL APPLICATIONS:

• Use as a tissue sealant that offers direct biodegradation for removal

• The use as a drug delivery system

• Paint additive for reductions in carbon footprint in manufacturing

• Use in hygiene industry (e.g., dental implants for improved mechanical robustness)

• Additionally, can be engineered to be suitable for more widespread applications:

- Promote cell adhesion/infiltration or prevent cell adhesion

- Promote tissue regeneration

- Provide blood clotting action       

- Substitute suture in anastomosis procedure without bonding to other biomedical devices,

- Applied to lesions on demand and further crosslinked upon visible light exposure

- Be easily removed from tissue in the case of unwanted application

- Be involved in minimally-invasive medical procedures

 

ADVANTAGES:

• Enables the fine-tuning of sealing properties of hydrogels without significantly changing biodegradation potential, swelling, and other physical properties pertinent to successful clinical translation

• Enhances the tissue sealing properties of naturally derived hydrogels beyond the performance of commercially available sealants using a facile hybridization method

 

DEVELOPMENT-TO-DATE:

The biopolymer composition has been successfully developed and tested against single component hydrogels. Furthermore, the biopolymer composition has been shown to form an effective tissue adhesive gel able to seal defects in tissue and prevent leakage of bodily fluid.

 

RELATED PAPERS:
• Sani, E.S., Kheirkhah, A., Rana, D., Sun, Z., Foulsham, W., Sheikhi, A., Khademhosseini, A., Dana, R. and Annabi, N., 2019. Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels. Science advances, 5(3).

• Yue, K., Trujillo-de Santiago, G., Alvarez, M.M., Tamayol, A., Annabi, N. and Khademhosseini, A., 2015. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials, 73, pp.254-271.

• Annabi, N., Rana, D., Sani, E.S., Portillo-Lara, R., Gifford, J.L., Fares, M.M., Mithieux, S.M. and Weiss, A.S., 2017. Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing. Biomaterials, 139, pp.229-243.

• Annabi, N., Zhang, Y.N., Assmann, A., Sani, E.S., Cheng, G., Lassaletta, A.D., Vegh, A., Dehghani, B., Ruiz-Esparza, G.U., Wang, X. and Gangadharan, S., 2017. Engineering a highly elastic human protein–based sealant for surgical applications. Science translational medicine, 9(410).

• Noshadi, I., Hong, S., Sullivan, K.E., Sani, E.S., Portillo-Lara, R., Tamayol, A., Shin, S.R., Gao, A.E., Stoppel, W.L., Black III, L.D. and Khademhosseini, A., 2017. In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels. Biomaterials science, 5(10), pp.2093-2105.

• Nichol, J.W., Koshy, S.T., Bae, H., Hwang, C.M., Yamanlar, S. and Khademhosseini, A., 2010. Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials, 31(21), pp.5536-5544.

• Hutson, C.B., Nichol, J.W., Aubin, H., Bae, H., Yamanlar, S., Al-Haque, S., Koshy, S.T. and Khademhosseini, A., 2011. Synthesis and characterization of tunable poly (ethylene glycol): gelatin methacrylate composite hydrogels. Tissue Engineering Part A, 17(13-14), pp.1713-1723.

Patent Information:
For More Information:
Earl Weinstein
Associate Director of Business Development
eweinstein@tdg.ucla.edu
Inventors:
Ali Khademhosseini
Nasim Annabi
Amir Sheikhi