Introduction: With the recent advancement of laparoscopic and robotic surgeries, increasing demand exists for tissue adhesives and sealants as an alternative to suturing. We and other groups have been investigating synthetic adhesives to overcome limitations shown by those of biological origin (e.g., poor mechanical strength, potential viral transmission and hypersensitive reactions). Tetronic® is a family of 4-arm, PPO-PEO block copolymers, that can form thermoreversible gels in aqueous solutions. We previously reported that Tetronic 1107 was modified to incorporate acrylate (ACR) for chemical crosslinking and N-hydroxysuccinamide (NHS) to enhance tissue bonding; modifications that showed promising adhesive capabilities. However, handling these hydrogels is challenging since they gel rapidly at room temperature and show a relatively high degradation rate[1]. Our goal is to assess the impact of blending bifunctional T1107 with another acrylated Tetronic (T304-ACR) of lower molecular weight and different hydrophilic-lipophilic balance (HLB) on gelation temperature (GT) and degradation rates.
Materials and Methods: Hydrogels that consist of 30wt% blends of T1107-ACR-NHS and T304-ACR in PBS were prepared as previously reported[1],[2]. GTs were determined by rheometry (under constant dynamic strain of 1%, f=0.1 Hz, and temperature sweep, 4-40 ˚C) using 40-mm parallel stainless steel plate geometry and 150-µm gap. The values were defined as the crossing point between storage modulus (G’) and loss modulus (G”). Degradation profiles of Tetronic adhesives were defined as the percentage mass loss of crosslinked discs incubated in PBS at pH=7.4 and 37 ˚C[3]. Mass loss is defined as initial weight minus final weight over initial weight. Adhesive properties were evaluated through lap shear test. Specimens (4x1 cm) were prepared by firmly attaching a collagen sheet to a metal strip, and applying the adhesive sample to create a 1 cm2 contact area. Specimens were subjected to uniaxial load at 10 mm/min crosshead speed until failure[1].
Results and Discussion: Thermal gelation of the 100:0 (=T1107-ACR-NHS : T304-ACR) blend occurred at a mean value of 20.0 ˚C. Addition of increasing amounts of T304-ACR led to an increase in GTs; 23.7±2.0˚C, 26.0±1.0˚C and 36.0±2.8˚C for 75:25, 50:50, and 25:75 blends, respectively. The storage modulus G’ determined at 37˚C exhibited a drastic decrease with increasing T304-ACR contents, 49.01±10.34 kPa, 7.94±0.69 kPa, 1.72±0.05 kPa and 0.07±0.09 kPa for 100:0, 75:25, 50:50, and 25:75, respectively.
Blending of T304-ACR with T1107-ACT-NHS resulted in higher GTs, which could be expected from the properties of these polymers. T304 and T1107 are of different molecular sizes and HLB, due to different EO to PO ratios, leading to the dissimilar thermogelation behavior. The increase in GT will provide a longer handling time for the adhesive at room temperature prior to application. However, rapid thermal gelation upon contact with warm tissues and organs will be an ideal feature as it will remain in place while chemical crosslinking reaction takes place.
Conclusion: Blending different Tetronics has proven to be a possible route to control gelation temperature in Tetronic based adhesives. It must be noted that the temperature control comes at the expense of a drastic change in G’. Modifying polymer concentration may help identifying an ideal combination of GT and mechanical behavior for these Tetronic blends.
References:
[1] Sanders L. J Biomed Mater Res Part A. 2015, 103(3): 861-68
[2] Balakrishnan N. MS Thesis, Clemson University. 2013
[3] Cho E. Acta Biomater. 2009, 8(6):2223-2232