Amine-linked heteroporous covalent organic framework for synergistic anti-infective therapy of post-traumatic osteomyelitis.

Abstract

The treatment of post-traumatic osteomyelitis (PTO) is impeded by bacterial biofilms and disruption of drug delivery systems in acidic lesions. Here, we develop an acid-resistant amine-linked heteroporous covalent organic framework (ARCOF) using a reductive amination strategy. This approach overcomes the insufficient chemical stability and drug delivery capacity of conventional COFs arising from the trade-off between high bond strength and crystalline reversibility. The pre-designed hetero-environmental channels of ARCOF enable synergistic loading of vancomycin and the anti-biofilm agent felodipine. When combined with calcium phosphate cement, both drugs exhibit sustained release over 240 h under inflammatory conditions. The therapeutic efficacy is evaluated in a rat PTO model, where the co-delivery system significantly enhances antibacterial efficacy by disrupting biofilm integrity and concurrently modulates the local inflammatory microenvironment to support bone tissue recovery. This strategy provides an integrated local delivery approach to overcome pharmacokinetic barriers and biofilm resistance in osteomyelitis treatment.