Safe, injectable, elastomeric biomaterials to augment tissue volume and improve biomechanical functions during tissue regeneration remain as a significant clinical need. One example is preterm birth, which occurs in greater than 500,000 pregnancies per year, or 12.3% of all pregnancies in the U.S., and for which there remain poor clinical options. To address this need, in our recent studies we have developed a new family of silk protein-based elastomers with an extraordinary range of mechanical features and based on an FDA approved material. The features of these protein elastomers include tunable mechanics, tunable biodegradation, biocompatibility and options for growth factor decoration, suggesting a suitable match to the needs in the field of soft tissue augmentation. The hypothesis is that modulating silk elastomer formation and functionalization can provide a new family of injectable elastomers to meet a broad range of tissue augmentation needs, such as for the treatment of preterm birth. The planned studies build on our extensive preliminary data, with both fundamental biomaterials studies planned, combined with a targeted clinical application where new options are a current critical need. The goal is to restore cervical tissue functions and prevent preterm birth in instances where dysfunctional cervical tissue is the cause. The three Aims focus on optimizing the biomaterial properties to match mechanics, injectability and kinetics, in vitro assessments of mechanical and biological functions, and in vivo studies of cervical augmentation in a rabbit model.

Public Health Relevance

The need for soft tissue reconstruction for tissue fillers, repairs and delivery systems containing cells and/or growth factors has broad implications in clinical medicine, covering many specific tissues, from the urinary and reproductive track, to vocal cords to brain and dermis as well as other locations. In all of these instances, current biomaterial options are limited in terms of the goal towards tissue regeneration due to the use of nondegradable polymers that do not restore full tissue structure and function, or the use of degradable materials that are limited in matching key design needs. The study proposed here will provide new biomaterial options to address many of these soft tissue augmentation needs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB021264-03
Application #
9523319
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Rampulla, David
Project Start
2016-09-20
Project End
2020-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Tufts University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
073134835
City
Boston
State
MA
Country
United States
Zip Code
Liaudanskaya, Volha; Jgamadze, Dennis; Berk, Alexander N et al. (2018) Engineering advanced neural tissue constructs to mitigate acute cerebral inflammation after brain transplantation in rats. Biomaterials 192:510-522
Wang, Xue; Ding, Zhaozhao; Wang, Chen et al. (2018) Bioactive Silk Hydrogels with Tunable Mechanical Properties. J Mater Chem B 6:2739-2746
Brown, Joseph E; Tozzi, Lorenzo; Schilling, Benjamin et al. (2018) Biodegradable silk catheters for the delivery of therapeutics across anatomical repair sites. J Biomed Mater Res B Appl Biomater :
Raia, Nicole R; Partlow, Benjamin P; McGill, Meghan et al. (2017) Enzymatically crosslinked silk-hyaluronic acid hydrogels. Biomaterials 131:58-67
Koullali, Bouchra; Westervelt, Andrea R; Myers, Kristin M et al. (2017) Prevention of preterm birth: Novel interventions for the cervix. Semin Perinatol 41:505-510