Approximately 114 million surgical and procedure-based wounds occur annually worldwide, including 36 million from surgery in the U.S. Damages to delicate soft tissues, such as lung, liver, and blood vessels, are particularly challenging to repair. When these tissues are punched for biopsy or injured during procedures, they must be reconnected surgically using sutures, staples, or implantation of surgical meshes. Despite their common use in clinics, these mechanical methods are associated with inevitable tissue damages caused by deep piercing and ischemia. These methods are also time-consuming, demand surgeon's skills during the surgeries, and might cause post-surgical complications such as infection. To resolve these issues, various types of surgical materials have been used for sealing, reconnecting tissues, or attaching devices to tissues. Despite the emergence of several surgical sealants, the biomaterials used as sealants/adhesives often have some drawbacks that limit their applications, such as low mechanical flexibility, toxicity effects or toxic degradation products, poor adhesive strength, and inability to control bleeding. Therefore, none of them meet all the necessary needs to replace sutures and staples. An ideal surgical sealant is required to be flexible to adapt with dynamic movement of native tissues, have excellent biocompatibility and controlled biodegradability, provide high adhesive strength and burst pressure particularly in the presence of body fluids, and demonstrate hemostatic properties to prevent extensive blood loss. In this proposal, we aim to engineer a novel, highly adhesive and hemostatic hydrogel-based surgical sealant from a visible light activated, modified recombinant human protein methacryloyl tropoelastin (MeTro) and hemostatic silicate nanoparticles (SNs). We will physically blend the engineered MeTro hydrogels with SNs to form MeTro/SN composite hydrogels with highly adhesion and enhanced hemostatic performance. We will then evaluate the function of the engineered surgical material as a hemostatic sealant in both small and large animal models. Our preliminary data suggests that this material is superior to the existing products in the market and may generate a paradigm-shifting surgical material that may not require sutures due to its superior mechanical, adhesive, and hemostatic properties. The engineered highly adhesive and hemostatic surgical sealant can be potentially used to stop air leakages after lung surgery and also support new tissue formation to repair the defected sites. Due to the highly tunable properties of the engineered composite hydrogels, it is expected that this system can also be used in various procedures such as anastomoses, cardiovascular surgeries, and wound closure.

Public Health Relevance

Despite recent advances in the development of surgical materials, there are no clinically approved surgical adhesives/sealants that are highly elastic, hemostatic, nontoxic, bind strongly to tissues, and work well within the wet and highly dynamic body environments, in the presence of certain body fluids to prevent extensive blood loss. In this proposal, we aim to engineer a novel visible light activated, highly adhesive, and hemostatic surgical sealant from a modified recombined human protein and synthetic silicate nanoparticles, which can provide mechanical flexibility without compromising strength, adhere strongly to the native tissues to stop air/body fluid leakages after surgical procedures, and demonstrate hemostatic properties to prevent blood loss.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL140618-01
Application #
9460885
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lee, Albert
Project Start
2018-01-01
Project End
2021-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Northeastern University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
001423631
City
Boston
State
MA
Country
United States
Zip Code
02115