| Injectable filler materials have long been used to treat soft tissue defects such as facial scaring, skin fatigue and volume loss. The overwhelming interest in these materials has led to an increase in novel bio-inspired platforms to improve filler material integration and efficacy in modified tissue. This project focused on designing a dynamic array of injectable silk-based materials for soft tissue augmentation and reconstruction. Silk fibroin is a naturally derived, fibrous protein which is non-immunogenic and FDA-approved for reconstructive surgery. Furthermore, the processing capabilities of silk allow for the formation of a versatile set of material formats, such as films, tubes, hydrogels and sponges.;Three material formats were optimized for minimally invasive tissue bulking. Elastomeric silk hydrogels were formulated for cervical tissue bulking towards preterm birth prevention in patients with cervical insufficiency. Hydrogels were able to increase tissue volume of cervical samples without causing excessive stiffening, ultimately restoring the native properties of the cervix. Shape memory silk sponges were designed to express high flexibility and volumetric swelling in aqueous media. Under high compressive stress (up to 90% uniaxial strain), silk sponges could recovery up to and beyond their original volume without plastic deformation. Additionally, sponges promoted cellular infiltration and tissue deposition in vivo, allowing regeneration of the tissue surrounding the wounded area. Gradient porosity silk catheters were fabricated for integration with adipose tissue during fat grafting procedures. Catheters could sustain release of a cargo therapeutic for up to two weeks, and the gradient porosity allowed spatial control over the location of drug release along the tube length. Silk catheters improved in vivo volume retention of transplanted adipose tissue by supporting viability with targeted dexamethasone delivery. Finally, the mechanism behind creating flexible protein-based materials using naturally derived plasticizers was investigated. The findings reported here support future development of more advanced biomimetic tissue fillers capable of accommodating minimally invasive insertion strategies. |
