Development of polycarbonate urethane‐based materials with controlled diclofenac release for cartilage replacement

Abstract

Hydrogels are very promising human cartilage replacement materials since they are able to mimic its structure and properties. Besides, they can be used as platforms for drug delivery to reduce inflammatory postsurgical reactions. Polycarbonate urethane (PCU) has been used in orthopedic applications due to its long‐term biocompatibility and bio‐durability. In this work, PCU‐based hydrogels with the ability to release an anti‐inflammatory (diclofenac) were developed, for the first time, for such purpose. The materials were reinforced with different amounts of cellulose acetate (CA, 10%, 15%, and 25% w/w) or carbon nanotubes (CNT, 1% and 2% w/w) in order to improve their mechanical properties. Samples were characterized in terms of compressive and tensile mechanical behavior. It was found that 15% CA and 2% CNT reinforcement led to the best mechanical properties. Thus, these materials were further characterized in terms of morphology, wettability, and friction coefficient (CoF). Contrarily to CNTs, the addition of CA significantly increased the material's porosity. Both materials became more hydrophilic, and the CoF slightly increased for PCU + 15%CA. The materials were loaded by soaking with diclofenac, and drug release experiments were conducted. PCU, PCU + 15%CA and PCU + 2%CNT presented similar release profiles, being able to ensure a controlled release of DFN for at least 4 days. Finally, in vitro cytotoxicity tests using human chondrocytes were also performed and confirmed a high biocompatibility for the three studied materials.

Super‐Strong Hydrogel Composites Reinforced with PBO Nanofibers for Cartilage Replacement

“…To evaluate the possibility of using PVA–PBO composites as drug delivery platforms, 6P1Z_AUT samples were loaded with the anti‐inflammatories diclofenac (DFN) and ketorolac (KTL), medicines that are commonly prescribed for the relief of inflammatory symptoms after an orthopedic surgery, whose local‐level vehiculation may bring benefits in terms of efficiency and reduction of side effects. [ 27,50,55 ]…”

“…To evaluate the possibility of using PVA-PBO composites as drug delivery platforms, 6P1Z_AUT samples were loaded with the anti-inflammatories diclofenac (DFN) and ketorolac (KTL), medicines that are commonly prescribed for the relief of inflammatory symptoms after an orthopedic surgery, whose local-level vehiculation may bring benefits in terms of efficiency and reduction of side effects. [27,50,55] After autoclaving the composites in the different loading solutions, the materials were left to load for 1 week. The stability of both drugs in solution after steam heat sterilization has been confirmed in a previous study.…”

“…Due to the high water absorption and retention capacity of hydrogels, they can be easily loaded with bioactive molecules and release them later in a controlled manner. [49,50] Therefore, the possibility of using these materials as platforms for the local drug delivery in cartilage repair/replacement systems has sparked an increasing interest. They allow achieving adequate levels of therapeutic agents in the target tissues, overcoming the limitations of other administration forms (e.g., adverse side effects or need for higher doses of drugs in systemic administration).…”