Toward More Predictable Musculoskeletal Embolization: A Translational Evaluation of Imipenem–Cilastatin Performance and Safety in a Porcine Model of Tendon Neovascularization

Abstract

Background: There is a need to provide a translational evaluation of imipenem–cilastatin as an innovative musculoskeletal embolic agent by assessing its embolization efficacy, physicochemical behavior, and safety profile in a porcine model of intratendinous neovascularization. Materials and Methods: In vitro analyses were performed to assess size distribution and solubility of imipenem–cilastatin in iodinated contrast media (Visipaque®) for two commercial formulations (Tienam® and Sun®). A preclinical study was conducted on six pigs, with neovascularization induced via collagenase injection in the patellar tendon. Each animal received Tienam® embolization with Visipaque® on one side and Visipaque® alone on the contralateral side at D7 post induction, followed by angiographic evaluation at D14. Efficacy was assessed using a four-point neovascularization score. Safety was evaluated through behavioral monitoring and rectal flora analysis. Results: In vitro, imipenem–cilastatin exhibited heterogeneous particle morphology and size: D50 was similar between Tienam® and Sun®, whereas D90 was markedly larger in Tienam® than Sun®, with limited solubility in Visipaque®. In vivo, Tienam® embolization led to variable reductions in neovascularization, ranging from complete to absent response (mean score decrease: 1.3 vs. 0.2 in controls, p = 0.07). Microbiological analysis revealed alterations in the rectal flora of all animals, with emergence of intrinsically carbapenem-resistant environmental species in four pigs, without evidence of acquired resistance. Conclusions: Imipenem–cilastatin demonstrates technical feasibility as a musculoskeletal embolic agent, but its efficacy remains heterogeneous, likely because of crystal irregularity and a broad size distribution. Although the procedure was clinically tolerated, the observed microbiota changes raise concerns regarding long-term safety and broader clinical adoption. Future research should focus on calibrated formulations that preserve embolic efficacy while improving reproducibility and minimizing off-target microbiological impact.