Formulation and characterization of poloxamine-based hydrogels as tissue sealants

Abstract

In-situ crosslinkable polyethylene glycol (PEG)-based polymers play an increasing role in surgical practice as sealants that provide a barrier to fluid/gas leakage and adhesion formation. This study investigated the gelation behavior and physical properties of hydrogels formed from homogeneous and blended solutions of two acrylated poloxamines (Tetronics® T1107 and T904) of varying molecular weight and hydrophilic/lipophilic balance relative to a PEG control. Hydrogels were formed by reverse thermal gelation at physiological temperature (T1107-containing formulations) and covalent crosslinking by Michael-type addition with dithiothreitol. All poloxamine-based hydrogels exhibited thermosensitive behavior and achieved significantly reduced swelling, increased tensile properties, and increased tissue bond strength relative to the PEG hydrogel at physiological temperature. Swelling and tensile properties of all poloxamine-based hydrogels were significantly greater at 37 °C relative to 4 °C, suggesting that their improved physical properties derive from cooperative crosslinking by both noncovalent and covalent mechanisms. Poloxamine-based hydrogels were cytocompatible and underwent hydrolytic degradation over 2 to 5 weeks depending on their T1107/T904 composition. In conclusion, select poloxamine-based hydrogels possess a number of properties potentially beneficial to tissue sealant applications including substantial increase in viscosity between room/physiological temperatures, resistance to cell adhesion, and maintenance of stable volume during equilibration.

Mechanically Robust, Negative‐Swelling, Mussel‐Inspired Tissue Adhesives

“…[31–34] A number of studies have previously reported chemically cross-linked Tetronic ® gels prepared by polymerization of terminal reactive functional groups. [31,36–44] …”

“…[31–35] Block copolymers of PPO and PEO, including commercially available multi-arm block copolymers composed of central PPO blocks and peripheral PEO blocks (Tetronic ® ), exhibit interesting thermosensitive behavior due to the hydrophilic-to-hydrophobic transition of the PPO block that occurs by mild warming. [31–34] Previous reports of chemically cross-linked Tetronic ® hydrogels for cell encapsulation and tissue adhesion have appeared in the literature, [31,36–44] though systematic studies of the relationship between chemical cross-linking, thermal transition, and mechanical properties in the context of medical adhesion have not been undertaken.…”

Tetronic®-based composite hydrogel scaffolds seeded with rat bladder smooth muscle cells for urinary bladder tissue engineering applications

“…The percent acrylation efficiency was calculated based on the ratio of the integrals of the PEG backbone (δ=3.5–3.7) and acrylic peaks (δ=6.15–6.4) (Figure 2) as previously shown in studies done by Cho et al (27) A yield of 22.5 g of T1107A was obtained from the original 30g of T1107 used in the synthesis and T1107A having more than 85% acrylation efficiency was used in the experiments. Efficient removal of unreacted acryloyl chloride was confirmed by the ratio of acrylate to activated PEG terminal (δ=4.3) methylene peaks, which closely approximated the theoretical value, 3:2.…”

“…(25) Briefly, T1107 (30g; 2 nmol) was dehydrated by azeotropic distillation for 2 h with toluene, which was then removed by rotary evaporation (Buchi Rotavapor®, Switzerland). After being cooled to room temperature, the dried T1107 was dissolved in 270 ml dehydrated dichloromethane and mixed with TEA (1.694 ml; 8 mmol).…”

“…The final product was recovered by filtration, dried for 48 h in a vacuum desiccator and stored at 4°C until use. (25) The NMR (Bruker Avance III 300, USA) spectra obtained on the final product was used to determine its acrylation efficiency.…”