High-Precision 3D Printing of Microporous Cochlear Implants for Personalized Local Drug Delivery.

Hearing loss is a highly prevalent multifactorial disorder affecting 20% of the global population. Current treatments using the systemic administration of drugs are therapeutically ineffective due to the anatomy of the cochlea and the existing blood-labyrinth barrier. Local drug delivery systems can ensure therapeutic drug concentrations locally while preventing adverse effects caused by high dosages of systemically administered drugs. Here, we aimed to design, fabricate, and characterize a local drug delivery system for the human cochlea. The design was relevant to the size of the human ear, included two different shapes, and incorporated two different microporous structures acting as reservoirs for drug loading and release. The four cochlear implant designs were printed using the two-photon polymerization (2PP) technique and the IP-Q photoresist. The optimized 2PP process enabled the fabrication of the cochlear implants with great reproducibility and shape fidelity. Rectangular and cylindrical implants featuring cylindrical and tapered tips, respectively, were successfully printed. Their outer dimensions were 0.6 × 0.6 × 2.4 mm3 (L × W × H). They incorporated internal porous networks that were printed with high accuracy, yielding pore sizes of 17.88 ± 0.95 µm and 58.15 ± 1.62 µm for the designed values of 20 µm and 60 µm, respectively. The average surface roughness was 1.67 ± 0.24 µm, and the water contact angle was 72.3 ± 3.0°. A high degree of polymerization (~90%) of the IP-Q was identified after printing, and the printed material was cytocompatible with murine macrophages. The cochlear implants designed and 3D printed in this study, featuring relevant sizes for the human ear and tunable internal microporosity, represent a novel approach for personalized treatment of hearing loss through local drug delivery.

In Vivo Prevention of Implant-Associated Infections Caused by Antibiotic-Resistant Bacteria through Biofunctionalization of Additively Manufactured Porous Titanium.

Additively manufactured (AM) porous titanium implants may have an increased risk of implant-associated infection (IAI) due to their huge internal surfaces. However, the same surface, when biofunctionalized, can be used to prevent IAI. Here, we used a rat implant infection model to evaluate the biocompatibility and infection prevention performance of AM porous titanium against bioluminescent methicillin-resistant Staphylococcus aureus (MRSA). The specimens were biofunctionalized with Ag nanoparticles (NPs) using plasma electrolytic oxidation (PEO). Infection was initiated using either intramedullary injection in vivo or with in vitro inoculation of the implant prior to implantation. Nontreated (NT) implants were compared with PEO-treated implants with Ag NPs (PT-Ag), without Ag NPs (PT) and infection without an implant. After 7 days, the bacterial load and bone morphological changes were evaluated. When infection was initiated through in vivo injection, the presence of the implant did not enhance the infection, indicating that this technique may not assess the prevention but rather the treatment of IAIs. Following in vitro inoculation, the bacterial load on the implant and in the peri-implant bony tissue was reduced by over 90% for the PT-Ag implants compared to the PT and NT implants. All infected groups had enhanced osteomyelitis scores compared to the noninfected controls.

Drug release from PLGA microspheres attached to solids using supercritical CO2.

Functionalization of a porous orthopedic implant with dexamethasone, a widely used anti-inflammatory drug, encapsulated within a biodegradable polymer for controlled release could help reduce or eliminate the inflammation response by the local tissue. In this research, we investigated the possibility of using supercritical carbon dioxide (CO2) for attaching dexamethasone-loaded PLGA (polylactic-co-glycolic acid) microspheres to porous CoCrMo alloy for continuous delivery of dexamethasone. Supercritical CO2 has been shown to be effective for attachment of PLGA microspheres to glass plates and porous CoCrMo alloy. Attached microspheres showed similar dexamethasone release profiles but different magnitude of burst release. Microspheres attached to the porous alloy samples using supercritical CO2 at 10 bar and 40 °C for 30 min showed a release profile similar to that of the nonattached microspheres. The microsphere morphology and the release profiles of microspheres attached to the glass plates and to the porous alloy samples suggest that dexamethasone burst release is enhanced by PLGA swelling at higher CO2 pressures and better dispersion of microspheres. This study shows that microspheres can be incorporated into porous solids using supercritical CO2, allowing for a wide variety of drug-biodegradable polymer formulations prepared using the proven emulsion/solvent evaporation method to be tested.