Biocompatibility of a Sonicated Silk Gel for Cervical Injection During Pregnancy: In Vivo and In Vitro Study

Critchfield, Agatha; McCabe, Reid; Klebanov, Nikolai; Richey, Lauren; Socrate, Simona; Norwitz, Errol R.; Kaplan, David L.; House, Michael

doi:10.1177/1933719114522551

Cited by 21 publications

(15 citation statements)

References 44 publications

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“…Not surprisingly therefore, the implantation of silk materials often induces the formation of FBGCs. This has been observed in a wide range of silk materials implanted in various locations including in scaffolds used to improve healing of bone defects (22, 30), gels injected in the cervix (25), and macroporous silk constructs implanted in fascial defects (14). …”

Section: Mechanism Of Silk Degradationmentioning

confidence: 94%

In vivo bioresponses to silk proteins

2015

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Silks are appealing materials for numerous biomedical applications involving drug delivery, tissue engineering, or implantable devices, because of their tunable mechanical properties and wide range of physical structures. In addition to the functionalities needed for specific clinical applications, a key factor necessary for clinical success for any implanted material is appropriate interactions with the body in vivo. This review summarizes our current understanding of the in vivo biological responses to silks, including degradation, the immune and inflammatory response, and tissue remodeling with particular attention to vascularization. While we focus in this review on silkworm silk fibroin protein due to the large quantity of in vivo data thanks to its widespread use in medical materials and consumer products, spider silk information is also included if available. Silk proteins are degraded in the body on a time course that is dependent on the method of silk fabrication and can range from hours to years. Silk protein typically induces a mild inflammatory response that decreases within a few weeks of implantation. The response involves recruitment and activation of macrophages and may include activation of a mild foreign body response with the formation of multinuclear giant cells, depending on the material format and location of implantation. The number of immune cells present decreases with time and granulation tissue, if formed, is replaced by endogenous, not fibrous, tissue. Importantly, silk materials have not been demonstrated to induce mineralization, except when used in calcified tissues. Due to its ability to be degraded, silk can be remodeled in the body allowing for vascularization and tissue ingrowth with eventual complete replacement by native tissue. The degree of remodeling, tissue ingrowth, or other specific cell behaviors can be modulated with addition of growth or other signaling factors. Silk can also be combined with numerous other materials including proteins, synthetic polymers, and ceramics to enhance its characteristics for a particular function. Overall, the diverse array of silk materials shows excellent bioresponses in vivo with low immunogenicity and the ability to be remodeled and replaced by native tissue making it suitable for numerous clinical applications.

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Section: Mechanism Of Silk Degradationmentioning

confidence: 94%

In vivo bioresponses to silk proteins

2015

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“…18 Using rats as a model for pregnancy, the cervical inflammatory response to an injected silk gel was similar to the response seen with suture controls. Cervical fibroblasts were seen to be viable, metabolically active, and proliferating on a silk surface.…”

Section: Potential For Novel Treatmentmentioning

confidence: 80%

Innovative Methods of Cervical Assessment and Potential for Novel Treatment

Feltovich¹,

House²

2014

Clinical Obstetrics &Amp; Gynecology

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A multitude of pathophysiologic pathways culminate in the final common denominator of cervical softening, shortening and dilation that lead to preterm birth. Currently, a variety of emerging technology aims to objectively quantify critical cervical parameters such as microstructural organization and softening of the cervix. If the nature and timing of cervical changes can be precisely identified, it should be possible to identify the causative upstream molecular processes and resultant biomechanical events associated with each unique pathway. This would promote molecular studies, ultimately leading to novel approaches to preterm birth prediction, novel treatments, and prevention.

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“…37–39 Sterile, sonicated silk was prepared as previously described. 30 Injections were performed via a midline laparotomy approach according to an IACUC approved protocol. Cervical injections were performed on gestational day 15.…”

Section: Injectable Biomaterials For Cervical Augmentationmentioning

confidence: 99%

Prevention of preterm birth: Novel interventions for the cervix

Koullali

Westervelt

Myers

et al. 2017

Seminars in Perinatology

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Preterm birth is the leading cause of neonatal mortality and morbidity worldwide. Spontaneous preterm birth is a complex, multifactorial condition in which cervical dysfunction plays an important role in some women. Current treatment options for cervical dysfunction include cerclage and supplemental progesterone. In addition, cervical pessary is being studied in research protocols. However, cerclage, supplemental progesterone and cervical pessary have well known limitations and there is a strong need for alternate treatment options. In this review, we discuss two novel interventions to treat cervical dysfunction: (1) injectable, silk protein-based biomaterials for cervical tissue augmentation (injectable cerclage) and (2) a patient-specific pessary. Three-dimensional computer simulation of the cervix is performed to provide a biomechanical rationale for the interventions. Further development of these novel interventions could lead to new treatment options for women with cervical dysfunction.

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Biocompatibility of a Sonicated Silk Gel for Cervical Injection During Pregnancy: In Vivo and In Vitro Study

Cited by 21 publications

References 44 publications

In vivo bioresponses to silk proteins

In vivo bioresponses to silk proteins

Innovative Methods of Cervical Assessment and Potential for Novel Treatment

Prevention of preterm birth: Novel interventions for the cervix

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