Online

Fenn, Spencer Lincoln

Bioengineering Graduate Program

2017

PhD

Pneumothorax, or a collapsed lung, is a serious medical condition resulting when air or fluid escapes the lung into the chest cavity and prevents the lung from inflating. Few viable means of sealing the damaged and leaking tissues are currently available, leading to longer hospital stays, multiple interventions, and increasing costs of care. The motivation of this dissertation is to engineer a novel polysaccharide-based therapeutic surgical sealant, which can be utilized to seal trauma-induced damage to the outer lining of the lung, i.e. pleura, preventing or reversing lung collapse to restore normal breathing function. The use of polysaccharides, such as alginate and hyaluronan, has become increasingly prevalent in biomedical and tissue engineering applications due to the ability to add functionality through chemical modification, allowing for tunable mechanical and physical properties. These hydrophilic polymer chains can be crosslinked to form hydrogels, which can retain large volumes of water and can mimic the properties of tissues found within the body. In this work, polysaccharide hydrogel sealants were engineered with well-regulated gelation and mechanical properties, and further modified to achieve adhesion to biological tissues. This was accomplished by mimicking the mechanical and physical properties of the complex tissues, and crosslinking the hydrogels in situ using a visible light-initiated system. Methacrylated alginate and oxidized alginate were successfully synthesized and utilized to fabricate adhesive sealant patches, which can adhere and seal damaged tissues in vivo. Methacrylation was implemented to allow covalent photo-crosslinking between adjacent polymer chains in solution. Here, a novel anhydrous chemistry was developed to allow for precise control over the degree of methacrylation and thus tune the mechanical properties of the resulting hydrogels by modulating the number of crosslinkable side-groups attached to the polysaccharide chain. To increase the adhesive properties of the resulting hydrogels, oxidation of the polysaccharide chain was subsequently implemented to form functional aldehyde groups capable of protein interactions through the formation of imine bonds on biological tissue surfaces. To test the performance of this multifunctional material, burst pressure testing was executed, revealing the relationship between the two distinct chemical modifications performed and the mechanical and adhesive properties of the resulting sealant. In addition, methacrylated alginate was utilized to synthesize therapeutic, drug-encapsulating hydrogel nanoparticles, which when incorporated within the polysaccharide-based surgical sealant allow for local drug release. The ability to control drug release at the site of application further broadens the potential uses of this surgical sealant patch and will be discussed further within this dissertation.