Development of novel hybrid 3D-printed degradable artificial joints incorporating electrospun pharmaceutical- and growth factor-loaded nanofibers for small joint reconstruction.

Small joint reconstruction remains challenging and can lead to prosthesis-related complications, mainly due to the suboptimal performance of the silicone materials used and adverse host reactions. In this study, we developed hybrid artificial joints using three-dimensional printing (3D printing) for polycaprolactone (PCL) and incorporated electrospun nanofibers loaded with drugs and biomolecules for small joint reconstruction. We evaluated the mechanical properties of the degradable joints and the drug discharge patterns of the nanofibers. Empirical data revealed that the 3D-printed PCL joints exhibited good mechanical and fatigue properties. The drug-eluting nanofibers sustainedly released teicoplanin, ceftazidime, and ketorolac in vitro for over 30, 19, and 30 days, respectively. Furthermore, the nanofibers released high levels of bone morphogenetic protein-2 and connective tissue growth factors for over 30 days. An in vivo animal test demonstrated that nanofiber-loaded joints released high concentrations of antibiotics and analgesics in a rabbit model for 28 days. The animals in the drug-loaded degradable joint group showed greater activity counts than those in the surgery-only group. The experimental data suggest that degradable joints with sustained release of drugs and biomolecules may be utilized in small joint arthroplasty.

Resorbable nanofibrous membranes for local and sustained co-delivery of acyclovir and ketorolac in herpes therapy.

Herpes simplex and herpes zoster are both viral infections caused by members of the herpesvirus family. The former is characterized by painful, fluid-filled blisters or sores on the skin and mucous membranes, while the latter presents as a painful rash with blisters, typically occurring in a single band or patch along one side of the body. The treatment remains a challenge since current antiviral therapy via oral administration may lead to unfavorable side effects such as headaches, nausea, and diarrhea. This study used electrospinning to develop biodegradable nanofibrous poly(lactic-co-glycolic acid) (PLGA) membranes for delivery of both acyclovir and ketorolac. The structure of the spun nanofibers was assessed via scanning electron microscopy (SEM), and the appearance of loaded acyclovir and ketorolac in the nanofibers was confirmed with Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Release profiles of these drugs from the nanofibrous membranes were assessed using in vitro elution studies, high-performance liquid chromatography (HPLC) assays, and in vivo drug release patterns. The electrospun nanofibers had a size range of 283-725 nm in diameter, resembling the extracellular matrix of natural tissue and demonstrated excellent flexibility and extensibility. Notably, the drug-eluting nanofibers exhibited an extended release of high levels of acyclovir and ketorolac over a 21-day period. Thus, biodegradable drug-eluting membranes with a prolonged drug release could be a potential therapeutic approach for treating herpes infections.

Novel Bioresorbable Drug-Eluting Mesh Scaffold for Therapy of Muscle Injury.

A novel bioresorbable drug-eluting polycaprolactone (PCL) mesh scaffold was developed, utilizing a solvent-cast additive manufacturing technique, to promote therapy of muscle injury. The degradation rate and mechanical properties strength of the PCL mesh were characterized after immersion in a buffer solution for different times. The in vitro release characteristics of vancomycin, ceftazidime, and lidocaine from the prepared mesh were evaluated using a high-performance liquid chromatography (HPLC) assay. In addition, the in vivo efficacy of PCL meshes for the repair of muscle injury was investigated on a rat model with histological examinations. It was found that the additively manufactured PCL meshes degraded by 13% after submission in buffered solution for four months. All PCL meshes with different pore sizes exhibited greater strength than rat muscle and survived through 10,000 cyclic loadings. Furthermore, the meshes could offer a sustained release of antibiotics and analgesics for more than 3 days in vitro. The results of this study suggest that drug-loaded PCL mesh exhibits superior ability to pure PCL mesh in terms of effectively promoting muscle repair in rat models. The histological assay also showed adequate biocompatibility of the resorbable meshes. The additively manufactured biodegradable drug-eluting meshes may be adopted in the future in humans for the therapy of muscle injuries.

Novel CO2-encapsulated Pluronic F127 hydrogel for the treatment of Achilles tendon injury.

Nonsurgical treatment and surgical repairment of injured Achilles tendons seldom restore the wounded tendon to its original elasticity and stiffness. Therefore, we hypothesized that the surgically repaired Achilles tendon can achieve satisfactory regeneration by applying multi-drug encapsulated hydrogels. In this study, a novel bupivacaine-eluting carbon dioxide-encapsulated Pluronic F127 hydrogel (BC-hydrogel) was developed for the treatment of Achilles tendon injuries. The rheological properties of BC-hydrogel were measured. A high-performance liquid chromatography assay was used to assess the release characteristics of bupivacaine in both in vitro and in vivo settings. Furthermore, the effectiveness of BC-hydrogel in treating torn tendons was examined in a rat model, and histological analyses were conducted. Evidently, the degradable hydrogels continuously eluted bupivacaine for more than 14 days. The animal study results revealed that the BC-hydrogel improved the post-surgery mobility of the animals compared with pristine hydrogels. Histological assay results demonstrated a significant reaction to high vascular endothelial growth factor in the surrounding tissues and expression of collagen I within the repaired tendon. This demonstrates the potential of this novel BC-hydrogel as an effective treatment method for Achilles tendon injuries.

Anti-Adhesive Resorbable Indomethacin/Bupivacaine-Eluting Nanofibers for Tendon Rupture Repair: In Vitro and In Vivo Studies.

The treatment and surgical repair of torn Achilles tendons seldom return the wounded tendon to its original elasticity and stiffness. This study explored the in vitro and in vivo simultaneous release of indomethacin and bupivacaine from electrospun polylactide-polyglycolide composite membranes for their capacity to repair torn Achilles tendons. These membranes were fabricated by mixing polylactide-polyglycolide/indomethacin, polylactide-polyglycolide/collagen, and polylactide-polyglycolide/bupivacaine with 1,1,1,3,3,3-hexafluoro-2-propanol into sandwich-structured composites. Subsequently, the in vitro pharmaceutic release rates over 30 days were determined, and the in vivo release behavior and effectiveness of the loaded drugs were assessed using an animal surgical model. High concentrations of indomethacin and bupivacaine were released for over four weeks. The released pharmaceutics resulted in complete recovery of rat tendons, and the nanofibrous composite membranes exhibited exceptional mechanical strength. Additionally, the anti-adhesion capacity of the developed membrane was confirmed. Using the electrospinning technique developed in this study, we plan on manufacturing degradable composite membranes for tendon healing, which can deliver sustained pharmaceutical release and provide a collagenous habitat.

Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models.

MicroRNA (miRNA) 107 expression is downregulated but Wnt3a protein and ß-catenin are upregulated in degenerated intervertebral disc (IVD). We investigated mir-107/Wnt3a-ß-catenin signaling in vitro and in vivo following hyperbaric oxygen (HBO) intervention. Our results showed 96 miRNAs were upregulated and 66 downregulated in degenerated nucleus pulposus cells (NPCs) following HBO treatment. The 3' untranslated region (UTR) of the Wnt3a mRNA contained the "seed-matched-sequence" for miR-107. MiR-107 was upregulated and a marked suppression of Wnt3a was observed simultaneously in degenerated NPCs following HBO intervention. Knockdown of miR-107 upregulated Wnt3a expression in hyperoxic cells. HBO downregulated the protein expression of Wnt3a, phosphorylated LRP6, and cyclin D1. There was decreased TOP flash activity following HBO intervention, whereas the FOP flash activity was not affected. HBO decreased the nuclear translocation of ß-catenin and decreased the secretion of MMP-3 and -9 in degenerated NPCs. Moreover, rabbit serum KS levels and the stained area for Wnt3a and ß-catenin in repaired cartilage tended to be lower in the HBO group. We observed that HBO inhibits Wnt3a/ß-catenin signaling-related pathways by upregulating miR-107 expression in degenerated NPCs. HBO may play a protective role against IVD degeneration and could be used as a future therapeutic treatment.

Hybrid Resorbable 3D-Printed Mesh/Electrospun Nanofibrous Drug/Biomolecule-Eluting Mats for Alveolar Ridge Preservation.

In this research study, we developed hybrid resorbable three-dimensional (3D)-printed mesh/electrospun nanofibrous biomolecule-eluting mats for alveolar ridge preservation. The fabrication process involved the use of 3D printing and coaxial electrospinning technologies. Specifically, we utilized a lab-developed solution-extrusion 3D printer to fabricate polycaprolactone (PCL) meshes. Then, bi-layered poly(lactic-co-glycolic acid) (PLGA) nanofibrous membranes, which embedded ibuprofen and epidermal growth factor (EGF), were prepared utilizing electrospinning and coaxial electrospinning techniques, respectively. To ensure the quality of the produced mesh and spun nanofibers, we carried out a characterization process. Furthermore, we estimated the in vitro and in vivo release characteristics of ibuprofen and EGF, respectively, using high-performance liquid chromatography and enzyme-linked immunosorbent assays. In addition, we assessed the effectiveness of hybrid nanofibrous mats for preserving the alveolar ridge by adopting an animal model and conducting a histology examination. The study findings demonstrate that the nanofibrous mats provided a continuous discharge of ibuprofen and EGF for more than four weeks. Moreover, the animal test carried out in vivo showed that animals implanted with this combination of mesh and drug-eluting mats displayed considerably greater mobility than those without mats. The histological analysis revealed no unfavorable impacts from the drug-eluting mats. Our study demonstrated the successful fabrication of resorbable drug-eluting nanofibrous mats for alveolar ridge preservation by utilizing both 3D printing and coaxial electrospinning technologies.

Thickness of simple calcaneal tuberosity avulsion fractures influences the optimal fixation method employed.

Aims: This study aimed to establish the optimal fixation methods for calcaneal tuberosity avulsion fractures with different fragment thicknesses in a porcine model. Methods: A total of 36 porcine calcanea were sawed to create simple avulsion fractures with three different fragment thicknesses (5, 10, and 15 mm). They were randomly fixed with either two suture anchors or one headless screw. Load-to-failure and cyclic loading tension tests were performed for the biomechanical analysis. Results: This biomechanical study predicts that headless screw fixation is a better option if fragment thickness is over 15 mm in terms of the comparable peak failure load to suture anchor fixation (headless screw: 432.55 N (SD 62.25); suture anchor: 446.58 N (SD 84.97)), and less fracture fragment displacement after cyclic loading (headless screw: 3.94 N (SD 1.76); suture anchor: 8.68 N (SD 1.84)). Given that the fragment thickness is less than 10 mm, suture anchor fixation is a safer option. Conclusion: Fracture fragment thickness helps in making the decision of either using headless screw or suture anchor fixation in treating calcaneal tuberosity avulsion fracture, based on the regression models of our study.

Nanofibrous insulin/vildagliptin core-shell PLGA scaffold promotes diabetic wound healing.

Introduction: Slow wound repair in diabetes is a serious adverse event that often results in loss of a limb or disability. An advanced and encouraging vehicle is wanted to enhance clinically applicable diabetic wound care. Nanofibrous insulin/vildagliptin core-shell biodegradable poly (lactic-co-glycolic acid) (PLGA) scaffolds to prolong the effective drug delivery of vildagliptin and insulin for the repair of diabetic wounds were prepared. Methods: To fabricate core-shell nanofibrous membranes, vildagliptin mixture with PLGA, and insulin solution were pumped via separate pumps into two differently sized capillary tubes that were coaxially electrospun. Results and Discussion: Nanofibrous core-shell scaffolds slowly released effective vildagliptin and insulin over 2 weeks in vitro migration assay and in vivo wound-healing models. Water contact angle (68.3 ± 8.5° vs. 121.4 ± 2.0°, p = 0.006) and peaked water absorbent capacity (376% ± 9% vs. 283% ± 24%, p = 0.003) of the insulin/vildagliptin core-shell nanofibrous membranes remarkably exceeded those of a control group. The insulin/vildagliptin-loaded core-shell nanofibers improved endothelial progenitor cells migration in vitro (762 ± 77 cells/mm2 vs. 424.4 ± 23 cells/mm2, p < 0.001), reduced the α-smooth muscle actin content in vivo (0.72 ± 0.23 vs. 2.07 ± 0.37, p < 0.001), and increased diabetic would recovery (1.9 ± 0.3 mm2 vs. 8.0 ± 1.4 mm2, p = 0.002). Core-shell insulin/vildagliptin-loaded nanofibers extend the drug delivery of insulin and vildagliptin and accelerate the repair of wounds associated with diabetes.

Sustained Release of Antifungal and Antibacterial Agents from Novel Hybrid Degradable Nanofibers for the Treatment of Polymicrobial Osteomyelitis.

This study aimed to develop a drug delivery system with hybrid biodegradable antifungal and antibacterial agents incorporated into poly lactic-co-glycolic acid (PLGA) nanofibers, facilitating an extended release of fluconazole, vancomycin, and ceftazidime to treat polymicrobial osteomyelitis. The nanofibers were assessed using scanning electron microscopy, tensile testing, water contact angle analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The in vitro release of the antimicrobial agents was assessed using an elution method and a high-performance liquid chromatography assay. The in vivo elution pattern of nanofibrous mats was assessed using a rat femoral model. The experimental results demonstrated that the antimicrobial agent-loaded nanofibers released high levels of fluconazole, vancomycin, and ceftazidime for 30 and 56 days in vitro and in vivo, respectively. Histological assays revealed no notable tissue inflammation. Therefore, hybrid biodegradable PLGA nanofibers with a sustainable release of antifungal and antibacterial agents may be employed for the treatment of polymicrobial osteomyelitis.

Enhanced Diabetic Wound Healing Using Electrospun Biocompatible PLGA-Based Saxagliptin Fibrous Membranes.

Delayed diabetic wound healing is an adverse event that frequently leads to limb disability or loss. A novel and promising vehicle for the treatment of diabetic wounds is required for clinical purposes. The biocompatible and resorbable poly (lactic-co-glycolic acid) (PLGA)-based fibrous membranes prepared by electrospinning that provide a sustained discharge of saxagliptin for diabetic wound healing were fabricated. The concentration of released saxagliptin in Dulbecco's phosphate-buffered saline was analyzed for 30 days using high-performance liquid chromatography. The effectiveness of the eluted saxagliptin was identified using an endothelial progenitor cell migration assay in vitro and a diabetic wound healing in vivo. Greater hydrophilicity and water storage were shown in the saxagliptin-incorporated PLGA membranes than in the pristine PLGA membranes (both p < 0.001). For diabetic wound healing, the saxagliptin membranes accelerated the wound closure rate, the dermal thickness, and the heme oxygenase-1 level over the follicle areas compared to those in the pristine PLGA group at two weeks post-treatment. The saxagliptin group also had remarkably higher expressions of insulin-like growth factor I expression and transforming growth factor-ß1 than the control group (p = 0.009 and p < 0.001, respectively) in diabetic wounds after treatment. The electrospun PLGA-based saxagliptin membranes exhibited excellent biomechanical and biological features that enhanced diabetic wound closure and increased the antioxidant activity, cellular granulation, and functionality.

Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by Angiogenesis.

The inhibition of dipeptidyl peptidase-4 (DPP4) significantly enhances the wound closure rate in diabetic patients with chronic foot ulcers. DPP4 inhibitors are only prescribed for enteral, but topical administration, if feasible, to a wound would have more encouraging outcomes. Nanofibrous drug-eluting poly-D-L-lactide-glycolide (PLGA) membranes that sustainably release a high concentration of vildagliptin were prepared to accelerate wound healing in diabetes. Solutions of vildagliptin and PLGA in hexafluoroisopropanol were electrospun into nanofibrous biodegradable membranes. The concentration of the drug released in vitro from the vildagliptin-eluting PLGA membranes was evaluated, and it was found that effective bioactivity of vildagliptin can be discharged from the nanofibrous vildagliptin-eluting membranes for 30 days. Additionally, the electrospun nanofibrous PLGA membranes modified by blending with vildagliptin had smaller fiber diameters (336.0 ± 69.1 nm vs. 743.6 ± 334.3 nm, p < 0.001) and pore areas (3405 ± 1437 nm2 vs. 8826 ± 4906 nm2, p < 0.001), as well as a higher hydrophilicity value (95.2 ± 2.2° vs. 113.9 ± 4.9°, p = 0.004), and showed a better water-retention ability within 24 h compared with PLGA membranes. The vildagliptin-eluting PLGA membrane also enhanced the diabetic wound closure rate for two weeks (11.4 ± 3.0 vs. 18.7 ± 2.6 %, p < 0.001) and the level of the angiogenesis using CD31 expression (1.73 ± 0.39 vs. 0.45 ± 0.17 p = 0.006 for Western blot; 2.2 ± 0.5 vs. 0.7 ± 0.1, p < 0.001 for immunofluorescence). These results demonstrate that nanofibrous drug-eluting PLGA membranes loaded with vildagliptin are an effective agent for sustained drug release and, therefore, for accelerating cutaneous wound healing in the management of diabetic wounds.

Pharmaceutical-eluting hybrid degradable hydrogel/microparticle loaded sacs for finger joint interpositional arthroplasty.

Despite recent advances in medical technology, treatment of chronic osteomyelitis in the small joint of the hand remains challenging. Here, we exploited hybrid biodegradable hydrogel/microparticle/polycaprolactone (PCL) sacs for finger joint interpositional arthroplasty via electrospraying and rotational molding techniques. Degradable Pluronic F127, poly(lactic-co-glycolic acid) (PLGA), and PCL were starting materials for the hydrogels, microparticles, and sac, respectively. Vancomycin, ceftazidime, and lidocaine were the embedded pharmaceuticals. The in vitro and in vivo drug release behaviors of hybrid drug-eluting sacs were assessed. The empirical outcomes show that the size distribution of the electrosprayed vancomycin/ceftazidime/lidocaine PLGA microparticles was 8.25 ± 3.35 µm. Biodegradable PCL sacs offered sustainable and effective release of vancomycin, ceftazidime, and lidocaine, respectively, after 30, 16, and 11 days in vitro. The sacs also discharged high levels of anti-microbial agents for 56 days and analgesics for 14 days in a rabbit knee joint model. The blood urea nitrogen (creatinine) levels remained normal at various time points: 16.5 ± 2.5 mg/dL (0.85 ± 0.24 mg/dL), 20.0 ± 1.4 mg/dL (1.0 ± 0.16 mg/dL), 19.3 ± 2.4 mg/dL (1.13 ± 0.15 mg/dL), and 20.0 ± 2.16 mg/dL (1.0 ± 0.16 mg/dL) at days 7, 14, 21, and 35, respectively. The empirical outcomes of this study suggested that the hybrid biodegradable drug-eluting sacs with extended liberation of pharmaceuticals may find applications in the small joints for post-operative pain relief and infection control.

Tri-Layered Doxycycline-, Collagen- and Bupivacaine-Loaded Poly(lactic-co-glycolic acid) Nanofibrous Scaffolds for Tendon Rupture Repair.

Achilles tendon rupture is a severe injury, and its optimal therapy remains controversial. Tissue engineering scaffolds play a significant role in tendon healing and tissue regeneration. In this study, we developed tri-layered doxycycline/collagen/bupivacaine (DCB)-composite nanofibrous scaffolds to repair injured Achilles tendons. Doxycycline, collagen, and bupivacaine were integrated into poly(lactic-co-glycolic acid) (PLGA) nanofibrous membranes, layer by layer, using an electrospinning technique as healing promoters, a 3D scaffold, and painkillers, respectively. After spinning, the properties of the nanofibrous scaffolds were characterized. In vitro drug discharge behavior was also evaluated. Furthermore, the effectiveness of the DCB-PLGA-composite nanofibers in repairing ruptured Achilles tendons was investigated in an animal tendon model with histological analyses. The experimental results show that, compared to the pristine PLGA nanofibers, the biomolecule-loaded nanofibers exhibited smaller fiber size distribution and an enhanced hydrophilicity. The DCB-composite nanofibers provided a sustained release of doxycycline and bupivacaine for over 28 days in vivo. Additionally, Achilles tendons repaired using DCB-composite nanofibers exhibited a significantly higher maximum load-to-failure than normal tendons, suggesting that the biomolecule-incorporated nanofibers are promising scaffolds for repairing Achilles tendons.

Electrospun, Resorbable, Drug-Eluting, Nanofibrous Membranes Promote Healing of Allograft Tendons.

In spite of advances in medical technology, the repair of Achilles tendon ruptures remains challenging. Reconstruction with an autograft tendon provides the advantage of a higher healing rate; nevertheless, the development of donor-site morbidity cannot be ignored. We developed biodegradable, drug-eluting, nanofibrous membranes employing an electrospinning technique and evaluated their effectiveness on the healing of allograft tendons. Poly-D-L-lactide-glycolide was used as the polymeric material for the nanofibers, while doxycycline was selected as the drug for delivery. The in vitro and in vivo drug-release profiles were investigated. The biomechanical properties of allografted Achilles tendons repaired using the nanofibrous membranes were tested in euthanized rabbits at 2-, 4-, and 6-week time intervals. Histological examination was performed for the evaluation of tissue reaction and tendon healing. The level of postoperative animal activity was also monitored using an animal behavior cage. The experimental results showed that the degradable nanofibers used as a vehicle could provide sustained release of doxycycline for 42 days after surgery with very low systemic drug concentration. Allograft Achilles tendon reconstruction assisted by drug-loaded nanofibers was associated with better biomechanical properties at 6 weeks post-surgery. In addition, the animals exhibited a better level of activity after surgery. The use of drug-eluting, nanofibrous membranes could enhance healing in Achilles tendon allograft reconstruction surgery.

Simvastatin-Loaded Nanofibrous Membrane Efficiency on the Repair of Achilles Tendons.

Introduction: In this study, simvastatin-incorporated poly(D,L-lactide-co-glycolide) (PLGA) nanofibrous mats were fabricated via electrospinning, and their efficacy in the repair of the Achilles tendon was evaluated. Methods: The morphology of spun nanofibers and the in vitro drug release kinetics were assessed, while the in vivo efficacy in tendon repair was tested using a rat model. Results: Images obtained by scanning electron microscopy revealed that spun nanofibers exhibit a porous structure with a fiber diameter of approximately 350 nm. Fourier-transform infrared spectrometry and differential scanning calorimetry demonstrated successful incorporation of pharmaceutical agents into the PLGA nanofibers. The drug-loaded nanofibrous membranes sustainably discharged high concentrations of simvastatin for >28 days at the target site, and drug concentrations in blood were low. Tendons repaired using simvastatin-eluting nanofibers exhibited superior mechanical strength and animal activities to those repaired without nanofibers or with pure PLGA nanofibers. Discussion: Simvastatin-loaded nanofibers demonstrated effectiveness and sustainable capability for the repair of Achilles tendons. Eventually biodegradable drug-eluting nanofibrous mats may be used in humans for the treatment of tendon ruptures.

Bone Morphogenetic Protein-, Antimicrobial Agent-, and Analgesic-Incorporated Nanofibrous Scaffolds for the Therapy of Alveolar Clefts.

An alveolar cleft is a bone defect in the maxillary arch. Although the use of autologous iliac bone grafts to repair alveolar clefts is the preferred treatment method, donor-site morbidity remains a concern. In this study, we incorporated bone morphogenetic protein (BMP), an antimicrobial agent, and an analgesic into nanofibrous scaffolds for alveolar cleft therapy. Three-dimensional (3D) printing and coaxial electrospinning techniques were used to fabricate the scaffolds. BMP-2, ketorolac, and amoxicillin were used as the growth factor, analgesic, and antimicrobial agent, respectively. The in vitro properties of the nanofibrous scaffolds were characterized, and in vivo efficacy was evaluated in a rat alveolar-cleft model. The empirical data indicated that the biomolecule-incorporated scaffolds offered extended discharge of BMP-2, amoxicillin, and ketorolac for >4 weeks. The animal test outcomes also demonstrated favorable bone healing at the cleft site. Biomolecule- and drug-incorporated nanofibrous scaffolds demonstrated their efficacy in alveolar cleft treatment.

Fabrication of Ropivacaine/Dexamethasone-Eluting Poly(D, L-lactide-co-glycolide) Microparticles via Electrospraying Technique for Postoperational Pain Control.

Microencapsulation plays an important role in biomedical technology owing to its particular and attractive characteristics. In this work, we developed ropivacaine and dexamethasone loaded poly(D, L-lactide-co-glycolide) (PLGA) microparticles via electrospraying technique and investigated the release behavior of electrosprayed microparticles. The particle morphology of sprayed particles was assessed using scanning electron microscopy (SEM). The in vitro drug release kinetics were evaluated employing an elution method, and the in vivo pharmaceutical release as well as its efficacy on pain relief were tested using an animal activity model. The microscopic observation suggested that sprayed microparticles exhibit a size distribution of 5-6 µm. Fourier-transform infrared spectrometry and differential scanning calorimetry demonstrated the successful incorporation of pharmaceuticals in the PLGA particulates. The drugs-loaded particles discharged sustainably high concentrations of ropivacaine and dexamethasone at the target region in vivo for over two weeks, and the drug levels in the blood remained low. By adopting the electrospraying technique, we were able to prepare drug-embedded polymeric microparticles with effectiveness and with a sustainable capability for postoperative pain control.

Novel Biodegradable 3D-Printed Analgesics-Eluting-Nanofibers Incorporated Nuss Bars for Therapy of Pectus Excavatum.

A novel hybrid biodegradable Nuss bar model was developed to surgically correct the pectus excavatum and reduce the associated pain during treatment. The scheme consisted of a three-dimensional (3D) printed biodegradable polylactide (PLA) Nuss bar as the surgical implant and electrospun polylactide-polyglycolide (PLGA) nanofibers loaded with lidocaine and ketorolac as the analgesic agents. The degradation rate and mechanical properties of the PLA Nuss bars were characterized after submersion in a buffered mixture for different time periods. In addition, the in vivo biocompatibility of the integrated PLA Nuss bars/analgesic-loaded PLGA nanofibers was assessed using a rabbit chest wall model. The outcomes of this work suggest that integration of PLA Nuss bar and PLGA/analgesic nanofibers could successfully enhance the results of pectus excavatum treatment in the animal model. The histological analysis also demonstrated good biocompatibility of the PLA Nuss bars with animal tissues. Eventually, the 3D printed biodegradable Nuss bars may have a potential role in pectus excavatum treatment in humans.

3D-printed/electrospun bioresorbable nanofibrous drug-eluting cuboid frames for repair of alveolar bone defects.

Despite progress in clinical science, the repair and restoration of alveolar bone defects remains as a challenge, particularly for nonuniform and complex defects. We developed bioresorbable nanofibrous drug-eluting cuboid frames for alveolar bone repair using three-dimensional (3D) printing and electrospinning technologies. The cuboid frames comprised polylactide (PLA) cages and ketorolac and amoxicillin-loaded poly(lactic-co-glycolic acid) nanofibers that imitated the morphology of the natural extracellular matrix of bone tissues. Characteristics of the printed frame and electrospun nanofibers were evaluated. The in vitro and in vivo release characteristics of the drugs embedded in the nanofibers were estimated using a high-performance liquid chromatography assay. In addition, the in vivo efficacies of the PLA cuboid frame and drug-eluting nanofibers for the treatment of alveolar bone defects were evaluated in a rat model. The experimental data indicated that the nanofibrous PLA frame provided a sustained release of ketorolac and amoxicillin for over 4 weeks. The results of the in vivo animal test also indicated that the animals that were implanted with the drug-eluting cuboid frame exhibited significantly greater movement than the animals with no frame. Histological analysis revealed no sign of adverse effects of the drug-eluting frames. By adopting 3D printing and electrospinning technologies, resorbable drug-eluting cuboid frames can be successfully manufactured for maxillofacial applications.