Direct Bonding of Chitosan Biomaterials to Tissues Using Transglutaminase for Surgical Repair or Device Implantation.

Natural biomaterials, such as chitosan and collagen, are useful for biomedical applications because they are biocompatible, mechanically robust, and biodegradable, but it is difficult to rapidly and tightly bond them to living tissues. In this study, we demonstrate that the microbial transglutaminase (mTG), can be used to rapidly (<5 min) bond chitosan and collagen biomaterials to the surfaces of hepatic, cardiac, and dermal tissues, as well as to functionalized polydimethylsiloxane (PDMS) materials that are used in medical products. The mTG-bonded chitosan patches effectively sealed intestinal perforations, and a newly developed two-component mTG-bonded chitosan spray effectively repaired ruptures in a breathing lung when tested ex vivo. The mechanical strength of mTG-catalyzed chitosan adhesive bonds were comparable to those generated by commonly used surgical glues. These results suggest that mTG preparations may be broadly employed to bond various types of organic materials, including polysaccharides, proteins, and functionalized inorganic polymers to living tissues, which may open new avenues for biomedical engineering, medical device integration, and tissue repair.

Biomaterial-based vaccine induces regression of established intracranial glioma in rats.

PURPOSE: The prognosis for glioma patients is poor, and development of new treatments is critical. Previously, we engineered polymer-based vaccines that control GM-CSF, CpG-oligonucleotide, and tumor-lysate presentation to regulate immune cell trafficking and activation, which promoted potent immune responses against peripheral tumors. Here, we extend the use of this system to glioma. METHODS: Rats were challenged with an intracranial injection of glioma cells followed (1 week) by administration of the polymeric vaccine (containing GM-CSF, CpG, and tumor-lysate) in the tumor bed. Control rats were treated with blank matrices, matrices with GM-CSF and CpG, or intra-tumoral bolus injections of GM-CSF, CpG, and tumor lysate. Rats were monitored for survival and tested for neurological function. RESULTS: Survival studies confirmed a benefit of the polymeric vaccine as 90% of vaccinated rats survived for > 100 days. Control rats exhibited minimal benefit. Motor tests revealed that vaccination protected against the loss of forelimb use produced by glioma growth. Histological analysis quantitatively confirmed a robust and rapid reduction in tumor size. Long-term immunity was confirmed when 67% of survivors also survived a second glioma challenge. CONCLUSIONS: These studies extend previous reports regarding this approach to tumor therapy and justify further development for glioma treatment.