RESUMO
Pelvic prolapse stands as a substantial medical concern, notably impacting a significant segment of the population, predominantly women. This condition, characterized by the descent of pelvic organs, such as the uterus, bladder, or rectum, from their normal positions, can lead to a range of distressing symptoms, including pelvic pressure, urinary incontinence, and discomfort during intercourse. Clinical challenges abound in the treatment landscape of pelvic prolapse, stemming from its multifactorial etiology and the diverse array of symptoms experienced by affected individuals. Current treatment options, while offering relief to some extent, often fall short in addressing the full spectrum of symptoms and may pose risks of complications or recurrence. Consequently, there exists a palpable need for innovative solutions that can provide more effective, durable, and patient-tailored interventions for pelvic prolapse. We manufactured an integrated polycaprolactone (PCL) mesh, reinforced with nano-hydroxyapatite (nHA), along with drug-eluting poly(lactic-co-glycolic acid) (PLGA) nanofibers for a prolapse scaffold. This aims to offer a promising avenue for enhanced treatment outcomes and improved quality of life for individuals grappling with pelvic prolapse. Solution extrusion additive manufacturing and electrospinning methods were utilized to prepare the nHA filled PCL mesh and drug-incorporated PLGA nanofibers, respectively. The pharmaceuticals employed included metronidazole, ketorolac, bleomycin, and estrone. Properties of fabricated resorbable scaffolds were assessed. The in vitro release characteristics of various pharmaceuticals from the meshes/nanofibers were evaluated. Furthermore, the in vivo drug elution pattern was also estimated on a rat model. The empirical data show that nHA reinforced PCL mesh exhibited superior mechanical strength to virgin PCL mesh. Electrospun resorbable nanofibers possessed diameters ranging from 85 to 540 nm, and released effective metronidazole, ketorolac, bleomycin, and estradiol, respectively, for 9, 30, 3, and over 30 days in vitro. Further, the mesh/nanofiber scaffolds also liberated high drug levels at the target site for more than 28 days in vivo, while the drug concentrations in blood remained low. This discovery suggests that resorbable scaffold can serve as a viable option for treating female pelvic organ prolapse.
RESUMO
We developed biodegradable drug-eluting prolapse mats using solution-extrusion 3D printing and coaxial electrospinning techniques. The mats were composed of polycaprolactone (PCL) mesh and lidocaine-, estradiol-, metronidazole-, and connective tissue growth factor (CTGF)-incorporated poly(lactic-co-glycolic acid) (PLGA) nanofibers that mimic the structure of the natural extracellular matrix of most connective tissues. The mechanical properties of degradable prolapse membrane were assessed and compared to commercial non-degradable polypropylene knitted meshes clinically used for pelvic organ prolapse (POP) repair. The release behaviors of the drug-loaded hybrid degradable membranes were also characterized. The experimental results suggest that 3D-printed PCL meshes exhibited comparable strengths to commercial POP meshes and survived through 10,000 cycles of fatigue test without breakage. Hybrid PCL meshes/PLGA nanofibrous membranes provided a sustainable release of metronidazole, lidocaine, and estradiol for 4, 25, and 30 days, respectively, in vitro. The membranes further liberated high levels of CTGF for more than 30 days. The animal tests show that the mechanical property of PCL mesh decreased with time, mainly due to degradation of the polymers post-implantation. No adverse effect of the mesh/nanofibers was noted in the histological images. By adopting solution-extrusion 3D printing and coaxial electrospinning, degradable drug-eluting membranes can be fabricated for POP applications.