A hybrid 3D-printed/electrospun biodegradable drug-eluting scaffold for heterotopic ossification-related local drug delivery
Heterotopic ossification (HO) is a clinically challenging complication after trauma or orthopedic surgery. This study evaluated a hybrid biodegradable scaffold for localized peri-osseous delivery of agents relevant to HO-risk and bone-healing environments. Polycaprolactone (PCL) mesh scaffolds were fabricated using solvent-cast additive manufacturing as flexible macro-scale barriers, while poly(lactic-co-glycolic acid) (PLGA) nanofibers incorporating indomethacin, teicoplanin, and bone morphogenetic protein-2 (BMP-2) were prepared using electrospinning and coaxial electrospinning. Scaffold morphology, wettability, mechanical behavior, Fourier-transform infrared spectroscopy and differential scanning calorimetry profiles, in vitro release, rabbit local/systemic release, and peri-implant histology were evaluated. The PCL mesh showed an ultimate tensile strength of 26.2 ± 2.6 MPa and a maximum strain of 337%. After 3 days in phosphate-buffered saline, the assembled PCL mesh/PLGA nanofiber scaffold retained comparable tensile properties, with an ultimate tensile strength of 24.8 ± 2.0 MPa and maximum strain of 334 ± 6%, indicating preserved flexibility under hydrated conditions. Drug-loaded PLGA nanofibers showed reduced tensile strength compared with pristine PLGA fibers, indicating that drug incorporation affected nanofiber handling and durability. In vitro testing demonstrated initial burst release of indomethacin and teicoplanin followed by sustained release, whereas BMP-2 release persisted for more than 30 days. In healthy rabbits, local teicoplanin and indomethacin levels were sustained for 28 days with substantially lower systemic levels. Histology demonstrated an early peri-implant inflammatory response that decreased over time. As no validated HO model or ectopic bone quantification was used, the findings support scaffold feasibility and localized delivery, not proven HO prevention. Further disease-model efficacy, biological activity, dose optimization, degradation, and safety studies are required before clinical translation.