Engineering a Highly Elastic Protein-based Surgical Sealant
Nasim Annabi1,2,3,4, Yi-Nan Zhang2,3, Alexander Assmann2,3,4, Andrea, Vegh2,3, George Cheng5, Bijan Dehghani2,3, Sidhu
Gangadharan5, Anthony Weiss6,7, Ali Khademhosseini2,3,4
1
Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
2
Biomaterials Innovation Research Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
3
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
4
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
5
Division of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
6
School of Molecular Bioscience, University of Sydney, Sydney, 2006, Australia.
7
Charles Perkins Centre, University of Sydney, Sydney, 2006, Australia.
Statement of Purpose: Approximately 114 million
surgical and procedure-based wounds occur annually
worldwide, including 36 million from surgeries in the US.
Post-operative reconnection of tissues is crucial for
restoring adequate function and structure. Sutures, wires,
and staples are widely used for this purpose. Despite their
common use in the clinic, these methods exhibit
limitations when being applied to fragile and soft tissues,
especially if the sealing is intended to prevent liquid or air
leakage against high pressure, as e.g. in vascular and lung
surgeries.. Various types of surgical materials have been
used for sealing, and reconnecting tissues, or attaching
devices to tissues. These surgical sealants/adhesives can
be used in adjunction with sutures for better closure or
even can potentially replace sutures and staples to close
the wound rapidly and improve clinical outcomes1.
However, existing surgical sealant materials often display
limited adhesive strength, toxicity, lack of appropriate
mechanical compliance and importantly, do not function
well in wet and dynamic environments in the body. To
address these limitations, we designed and developed a
novel human protein-based tissue sealant that combines
several critical characteristics and can outperform the
currently available sealant products in the market.
Methods: To fabricate the hydrogel-based adhesive,
methacrylated recombinant tropoelastin (MeTro) was
dissolved in distilled water and photocrosslinked with UV
light. The pore characteristics and swelling ratios of
MeTro hydrogels with different MeTro concentrations
and methacrylation degrees were evaluated. Tensile and
compressive cyclic tests on MeTro hydrogels were
performed using a mechanical tester (Instron model
5542). To study the adhesion strength of the MeTro gels
to the native tissues, wound closure, lap shear and burst
pressure tests were performed based on ASTM standards.
The biocompatibility of MeTro was studied by in vitro
tests and using an in vivo subcutaneous rat model. In
addition, the functionality of MeTro as a lung sealant was
tested in vivo using a rat lung incision model.
Results: An ideal surgical sealant is required to be highly
elastic to be able to adapt with dynamic movement of
native tissues, have excellent biocompatibility and
controlled biodegradability, and provide high adhesive
strength and burst pressure particularly in the presence of
body fluids. Therefore it is very important to tailor the
physical and biological properties of the biomaterials that
are used to engineer surgical sealants in accordance with
the indicated tissue. These biomaterials should also
rapidly polymerize in situ to seal the wound areas without
inducing toxicity. We have showed that UV crosslinkable
MeTro can produce a class of highly elastic, human
protein-based hydrogels with high biocompatibility2 (Fig.
1). MeTro exhibited tunable mechanical properties
depending on different MeTro concentrations and
methacrylation degrees. Adhesion strength of MeTro
sealant, measured by wound closure and lap shear tests,
showed properties superior to the clinical standard glues
such as Evicel and Coseal. Improved cell viability and
proliferation were achieved using MeTro gels in vitro.
Subcutaneous implantation also showed excellent
biocompatibility and material integration into the host
environment. In addition, burst pressure of MeTro sealant
covering a rat lung leakage was measured 7 days after
surgery. The value of bust pressure for the MeTro-sealed
lung was similar to that of healthy lung tissue, confirming
that MeTro sealed the incision and promoted lung tissue
healing.
Fig. 1. Photocrosslinking mechanism, pore
characteristics and tensile properties of MeTro
hydrogels.
Conclusions: A highly elastic, biocompatible, and
biodegradable hydrogel-based sealant was engineered
through photocrosslinking of a modified human protein.
Our in vitro and in vivo data suggest that this material is
superior to the existing products in the market and may
generate a paradigm-shifting surgical sealant that, due to
its excellent mechanical and adhesive properties, may not
require additionally supporting sutures.
References: (1) Annabi N, et al, Surgical Materials:
Current Challenges and Nano-enabled Solutions. Nano
Today. 2014;9(5):574-89. (2) Annabi N, et al, Engineered
cell-laden human protein-based elastomer. Biomaterials.
2013;34(22):5496-505.