Porous silk protein scaffolds were designed to display shape memory characteristics and volumetric recovery following compression. Two strategies were utilized to realize shape recovery: the addition of hygroscopic plasticizers like glycerol and tyrosine modifications with hydrophilic sulfonic acid chemistries. Silk sponges were evaluated for recovery following 80% compressive strain, total porosity and pore size distribution, secondary structure development, in vivo volume retention, cell infiltration, and inflammatory responses. Glycerol-modified sponges recovered up to 98.3% of their original dimensions following compression, while sulfonic acid / glycerol modified sponges swelled in water up to 71 times their compressed volume, well in excess of their original size. Longer silk extraction times (giving lower silk molecular weights) and higher concentrations of glycerol gave sponges with greater flexibility and shape fidelity, with no loss in modulus following compression. Sponges were over 95% porous, with secondary structure analysis indicating glycerol-induced β-sheet physical crosslinking. Tyrosine modifications with sulfonic acid interfered with β-sheet formation. Glycerol-modified sponges exhibited improved rates of cellular infiltration at subcutaneous implant sites with minimal immune response in mice. They also degraded more rapidly than unmodified sponges, a result posited to be cell-mediated. Overall, this work suggests that silk sponge systems may be useful for minimally invasive deployment in soft tissue augmentation procedures.
Background Cerclage therapy is an important treatment option for preterm birth prevention. Several patient populations benefit from cerclage therapy including patients with a classic history of cervical insufficiency; patients who present with advanced cervical dilation prior to viability; and patients with a history of prior preterm birth and cervical shortening. Although cerclage is an effective treatment option in some patients, it can be associated with limited efficacy and procedure complications. Development of an alternative to cerclage therapy would be an important clinical development. Here we report on an injectable, silk protein-based biomaterial for cervical tissue augmentation. The rationale for the development of an injectable biomaterial is to restore the native properties of cervical tissue. While cerclage provides support to the tissue, it does not address excessive tissue softening, which is a central feature of the pathogenesis of cervical insufficiency. Silk protein-based hydrogels, which are biocompatible and naturally degrade in vivo, are suggested as a platform for restoring the native properties of cervical tissue and improving cervical function. Objective We sought to study the properties of an injectable, silk-based biomaterial for potential use as an alternative treatment for cervical insufficiency. These biomaterials were evaluated for mechanical tunability, biocompatibility, facile injection and in vitro degradation. Study Design Silk protein solutions were crosslinked by an enzyme catalyzed reaction to form elastic biomaterials. Biomaterials were formulated to match the native physical properties of cervical tissue during pregnancy. The cell compatibility of the materials was assessed in vitro using cervical fibroblasts, and biodegradation was evaluated using concentrated protease solution. Tissue augmentation or bulking was demonstrated using human cervical tissue from non-pregnant hysterectomy specimens. Mechanical compression tests measured the tissue stiffness as a function of the volume of injected biomaterial. Results Silk protein concentration, molecular weight and concentration of crosslinking agent were varied to generate biomaterials that functioned from hard gels to viscous fluids. Biomaterials which matched the mechanical features of cervical tissues were chosen for further study. Cervical fibroblasts cultured on these biomaterials were proliferative and metabolically active over 6 days. Biomaterials were degraded in protease solution, with rate of mass loss dependent on silk protein molecular weight. Injection of cervical tissue samples with 100 μL of the biomaterial resulted in a significant volume increase (22.6% ± 8.8%, p<0.001) with no significant change in tissue stiffness. Conclusion Cytocompatible, enzyme-crosslinked silk protein biomaterials show promise as a tissue bulking agent. The biomaterials were formulated to match the native mechanical properties of human cervical tissue. These biomaterials should be explored further as a possible alternative to...
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