In Situ-gelling Materials for Drug Delivery and Tissue Reconstruction
- pdf version of the abstract

Significant interest exists in developing biomaterials that are injectable, in situ forming, and biodegradable. In fact, injectable, biodegradable materials have been investigated for numerous applications including drug delivery (1,2) cancer therapy (3), tissue reconstruction (4) and tissue engineering (5), such as orthopedic tissue engineering (2,6,7). Several material classes have been investigated for these applications; Injectable materials allow non-invasive (or less invasive) application of implanted biomaterials.
In cases where final shape is not important or must be defined by the local in vivo environment, the use of injectable and in situ forming materials is ideal. If the implant has a finite lifetime of use, the material would either have to be removed surgically, left in place or degrade. In these cases, degradation is preferred. An example of an application where the degradation would be essential are in orthopedic tissue engineering scaffolds where the materials must be displaced as the tissue grows to fill the injury.
Unfortunately, many current injectable biodegradable systems have various drawbacks including use of miscible organic solvents, or having to be preformed into microspheres, and release of low molecular weight degradation products. Other systems also require reactive chemistries (which can lead to toxicitiy or undesired side reactions in vivo) or photopolymerization (which requires access with an external light source.)

This presentation will review some of these systems seen in the literature and also present work in Dr. Vernon’s lab on these types of materials.

Two classes of in situ-gelling, injectable materials are being developed in Dr. Vernon’s lab: thermally reversible gels and self reactive crosslinking gels. Examples of two applications for these materials will be presented during the presentation. These are applications in localized delivery of cancer therapy agents and tissue augmentation in artervenous malformations.

(1) Hatefi, A. and B. Amsden (2002). “Biodegradable injectable in situ forming drug delivery systems.” Journal of Controlled Release 80(1-3): 9-28.
(2) Jeong, B., Y. H. Bae, et al. (1997). “Biodegradable block copolymers as injectable drug-delivery systems.” Nature 388(6645): 860-2.
(3) Emerich, D. F., S. R. Winn, et al. (2000). “Injectable chemotherapeutic microspheres and glioma I: enhanced survival following implantation into the cavity wall of debulked tumors.” Pharm Res 17(7): 767-75.
(4) Sims, C. D., P. E. Butler, et al. (1996). “Injectable cartilage using polyethylene oxide polymer substrates.” Plast Reconstr Surg 98(5): 843-50.
(5) Gutowska, A., B. Jeong, et al. (2001). “Injectable gels for tissue engineering.” Anatomical Record 263(4): 342-349.
(6) He, S., M. J. Yaszemski, et al. (2000). “Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate.” Biomaterials 21(23): 2389-94.
(7) Temenoff, J. S. and A. G. Mikos (2000). “Injectable biodegradable materials for orthopedic tissue engineering.” Biomaterials 21(23): 2405-12.
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Dr. Brent Vernon attended Arizona State University as an Undergrad, graduating in May 1993 in Biomedical Engineering. He completed his Ph.D. in Bioengineering in 1999 from the University of Utah. At the University of Utah, he worked toward the development of a “refillable/rechargeable biohybrid artificial pancreas” by encapsulating Islets of Langerhans in a Temperature Reversible Polymer gel. After Utah, he went to The University of Zurich/ETH in Zurich Switzerland for a Postdoc in biomaterials development. At the University of Zurich, he developed a new in situ gelling material for the treatment of intravertebral disc ruptures. Finally, he joined Arizona State University in August 2000 where he now works on injectable, in situ-gelling materials for drug delivery and tissue augmentation.