Publication
Tracheomalacia, a common congenital tracheal abnormality in pediatric airways, involves the dynamic collapse of the trachea due to weak cartilage rings or malfunctioning muscles. Severe cases cause significant respiratory distress, with current treatments yielding limited success and posing risks. This highlights the need for alternative solutions. Therefore, this thesis explores for the first time the use of adhesive hydrogels for treating tracheomalacia. To this end, an in-silico model was developed, which indicated that externally placed adhesive hydrogels could constrain muscle movement during collapse and maintain airway shape. Subsequently, an adhesive hydrogel based on hydroxyethyl acrylamide and polyethylene glycol dimethacrylate was formulated, which formed multiple physical interactions with the tracheal surface. During ex vivo tests, this hydrogel exhibited a shear adhesion strength of over 60 kPa and a tensile modulus of about 75 kPa. Micro-Chromatography imaging and ex vivo experiment showed that the hydrogel patch could prevent up to 50% of airway collapse. To improve the properties of hydroxyethyl acrylamide hydrogels, bifunctional polyethyleneglycol moieties, namely acrylamide-polyethyleneglycol-N-hydroxysuccinimide ester, were incorporated into hydroxyethyl acrylamide network, forming chemical bonds with tissue amine groups. This boosted the hydrogel's shear adhesive strength to over 90 kPa, increased its tensile modulus five-fold, reduced its swelling ratio by half, and improved its degradation time without toxicity to mouse fibroblast cells. Furthermore, ex vivo experiment showed that polyethyleneglycol-N-hydroxysuccinimide ester hydrogels reduced tracheal collapse by up to 90%. However, a necessary two-step polymerization process for adhesion posed challenges in vivo. To address this, dehydrated and rehydrated adhesive hydrogels based on acrylic acid, gelatin, and acrylamide-polyethyleneglycol-N-hydroxysuccinimide ester were developed. These dried and rehydrated gels showed up to a two-fold increase in adhesion compared to control samples. The dehydration process further enhanced the gel's mechanical strength and reduced its swelling ratio significantly in phosphate buffered saline. While ex vivo studies showed that rehydrated gels prevented up to 60% of airway collapse, they failed to attach to the trachea during in vivo tests due to blood and fluids. On the other hand, dried gels adhered well in vivo but could not maintain airway patency due to insufficient circumferential support. Overall, this thesis provides foundational insights into using adhesive hydrogels for tracheomalacia, potentially inspiring other biomedical applications.