Long-Term Degradation Assessment of a Polyurethane-Based Surgical Adhesive—Assessment and Critical Consideration of Preclinical In Vitro and In Vivo Testing

Abstract

Tissue adhesives constitute a great possibility to improve conventional wound closure. In contrast to sutures, they enable nearly immediate hemostasis and can prevent fluid or air leaks. In the present study, a poly(ester)urethane-based adhesive was investigated which already proved to be suitable for different indications, such as reinforcing vascular anastomosis and sealing liver tissue. Using in vitro and in vivo setups, the degradation of the adhesives was monitored over a period of up to 2 years, to evaluate long-term biocompatibility and determine degradation kinetics. For the first time, the complete degradation of the adhesive was documented. In subcutaneous locations, tissue residues were found after 12 months and in intramuscular locations, tissue degradation was complete after about 6 months. A detailed histological evaluation of the local tissue reaction revealed good biocompatibility throughout the different degradation stages. After full degradation, complete remodeling to physiological tissue was observed at the implant locations. In addition, this study critically discusses common issues related to the assessment of biomaterial degradation kinetics in the context of medical device certification. This work highlighted the importance and encouraged the implementation of biologically relevant in vitro degradation models to replace animal studies or at least reduce the number of animals in preclinical testing prior to clinical studies. Moreover, the suitability of frequently used implantation studies based on ISO 10993-6 at standard locations was critically discussed, especially in light of the associated lack of reliable predictions for degradation kinetics at the clinically relevant site of implantation.

Evaluation of the Hemostatic Effect of an Innovative Tissue Adhesive during Extraction Therapy under Rivaroxaban in a Rodent Model

“…In the histologic evaluation, VIVO showed comparable thrombus formations when compared to extraction sockets treated with GSP. In addition, the biodegradable polyurethane-based adhesive showed favorable immunologic properties in long-term studies [23,24]. VIVO comprises two components: a polyurethane prepolymer with reactive isocynate groups and an amino-based curing agent.…”

“…The novel polyurethane-based tissue adhesive VIVO (Adhesys Medical GmbH, Aachen, Germany) is an innovative biodegradable adhesive that has demonstrated rapid and safe application [20]. It is an alternative to conventional hemostasis [21][22][23] with favorable tissue compatibility [24], as evidenced by good biocompatibility during the various degradation phases [23]. The authors hypothesized that the use of polyurethane-based VIVO leads to a decrease in postoperative bleeding under good wound healing conditions after dental removal under rivaroxaban therapy.…”

Effect of the Advanced Cranial and Craniofacial Implant Fabrication on Their Degradation Affinity

“…A similar medium at various pH was applied to assess the degradation profile of the PEOT-PBT and poly(ester urethane) films [11]. Bremrer et al [12] used the guide of [13] for the evaluation of the degradation in vitro potentiality of the poly(ester)urethane-based adhesive. The simulated body fluid (SBF) at 37 • C was also used for the assessment of the degradation profile of the bi-layered 3D-printed scaffold with the PLA layer and PLA/bioglass G5 layer [14].…”

“…The profile of the in vitro degradation of the various usable forms and compositions containing PLA differed in relation to the content and proportion of the additives [4][5][6][7][8][9][10][11][12][13][14]. Bogdanova et al [15] received the 10% weight loss only during the in vitro degradation of the electrospun PLA-gelatin composition for 8 weeks in PBS and Fenton's solution.…”

“…This reduces the risk of non-compliant prototypes being subjected to in vivo testing (validation process) and does not compromise animal welfare. As indicated in [12], in vitro testing is indicated by regulatory authorities as indispensable to reduce the number of negative tests on animals. However, the results of these in vitro tests may not be sufficient to confirm the safety and performance of the medical device, as they are only a simplified research model.…”