Development of Tissue Adhesives Based on Amphiphilic Isocyanate‐ T erminated Trimethylene Carbonate Block Copolymers

Hannink

Janssen

et al. 2016

J Mater Sci: Mater Med

Self Cite

Isocyanate-terminated adhesive amphiphilic block copolymers are attractive materials to treat meniscus tears due to their tuneable mechanical properties and good adhesive characteristics. However, a drawback of this class of materials is their relatively long curing time. In this study, we evaluate the use of an amine cross-linker and addition of catalysts as two strategies to accelerate the curing rates of a recently developed biodegradable reactive isocyanate-terminated hyper-branched adhesive block copolymer prepared from polyethylene glycol (PEG), trimethylene carbonate, citric acid and hexamethylene diisocyanate. The curing kinetics of the hyper-branched adhesive alone and in combination with different concentrations of spermidine solutions, and after addition of 2,2-dimorpholinodiethylether (DMDEE) or 1,4-diazabicyclo [2.2.2] octane (DABCO) were determined using FTIR. Additionally, lap-shear adhesion tests using all compositions at various time points were performed. The two most promising compositions of the fast curing adhesives were evaluated in a meniscus bucket handle lesion model and their performance was compared with that of fibrin glue. The results showed that addition of both spermidine and catalysts to the adhesive copolymer can accelerate the curing rate and that firm adhesion can already be achieved after 2 h. The adhesive strength to meniscus tissue of 3.2–3.7 N was considerably higher for the newly developed compositions than for fibrin glue (0.3 N). The proposed combination of an adhesive component and a cross-linking component or catalyst is a promising way to accelerate curing rates of isocyanate-terminated tissue adhesives.

“…Analysis by 1 H-NMR after each synthesis step and FTIR confirmed that the adhesive hyper-branched block copolymers were successfully synthesized [12, 13]. …”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of a fast curing tissue adhesive for meniscus tear repair

Hannink

Janssen

et al. 2016

J Mater Sci: Mater Med

Self Cite

“…[14] The building blocks of the copolymer were trimethylolpropane ethoxylate (TMPE, M n = 450 g/mol), trimethylene carbonate (TMC), and hexamethylene diisocyanate (HDI).…”

Section: Experimental Tissue Adhesivesmentioning

confidence: 99%

Adhesion of tissue glues to different biological substrates

Polymers for Advanced Techs

Hannink

Buma

et al. 2016

Tissue adhesives are attractive materials with potential to replace the use of sutures and staples in the repair of the injured tissues. The research field of tissue adhesives is dynamically growing, and different methods and tissue models are employed to evaluate the adhesive properties of newly developed materials. It is thus difficult to directly compare the properties of materials developed by researchers from different groups. Moreover, the extrapolation of results obtained using different tissue models to the targeted human tissues is often not possible. Therefore, the purpose of the current study was to evaluate the adhesive properties of the three different tissues adhesives: the clinically used Dermabond W and fibrin glues, and the recently developed isocyanate-terminated three-armed adhesive block copolymers. Different biological substrates were used to assess their adhesion strengths: bovine Achilles tendon, meniscus tissue and skeletal muscle, chamois leather, and collagen films. Comparisons of the adhesive properties of the glues with these substrates were made. The obtained results were analyzed in terms of the chemistry and the adhesion mechanisms of the glues, and the composition and properties of the substrates like their hydrophilicity and surface morphology. We conclude that standardized procedures and models should be developed to allow direct comparison between the different (developed) tissue adhesives and to enable extrapolation of the results towards the targeted human tissues.

“…We recently reported on the development of reactive three-armed and hyper-branched block copolymeric tissue adhesives that can attach to the tissue via covalent bonding [17, 18] In a following study, meniscus explants were glued with these adhesives and cultured in vitro. It was shown that both developed materials have satisfactory bonding strengths to the tissue and did not exhibit toxicity to the cells, and therefore have the potential to be used in the treatment meniscal tears (unpublished work).…”

Section: Introductionmentioning

confidence: 99%

The effect of tissue surface modification with collagenase and addition of TGF-β3 on the healing potential of meniscal tears repaired with tissue glues in vitro

Hannink²,

Verhoeven³

et al. 2016

J Mater Sci: Mater Med

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The aim of the current in vitro study was to investigate if tissue surface modification with collagenase and addition of the TGF-β3 can increase the number of cells present in meniscus tears repaired with the use of newly developed tissue adhesives based on isocyanate-terminated block copolymers. Cylindrical explants were harvested from the inner part of bovine menisci. To simulate a full-thickness tear, the central core of the explants was removed and glued back into the defect, with or without incubation in collagenase solution prior to gluing. The repair constructs were then cultured with or without addition of TGF-β3, and assessed for their histological appearance. The histological staining of the constructs confirmed that both developed adhesives were not cytotoxic. After 28 days, meniscus cells were present in direct contact with the glues. The addition of TGF-β3 to the culture medium resulted in the presence of cells that formed a sheath inside the simulated tear and in increased cell numbers at the edges of annulus of the explants. In the group in which the tissue was incubated in collagenase and cultured in medium containing TGF-β3, thicker layers of cells were observed. These results suggest that repairing the torn meniscus with tissue adhesives after pre-treatment of the tissue with collagenase and stimulation with TGF-β3 is a very promising treatment method, especially when treating the inner avascular part of the meniscus. Nevertheless, longer-term in vitro and in vivo studies are needed to confirm the beneficial effects of this combination therapy.