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Abstract 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.

Antibiotic beads can be used to treat surgical infections. In this study, polylactide–polyglycolide (PLGA) was mixed with vancomycin, the osteogenic enhancer lithium chloride (LiCl), and hot compression to form PLGA-vancomycin-LiCl delivery beads to treat bone infection. An elution method was used to characterize in vitro release characteristics of vancomycin and Li over a 42-day period. The release profiles lasted for more than 42 days for vancomycin and 28 days for Li. The concentration of vancomycin in each sample was well above the breakpoint sensitivity. Lithium cotreatment enhanced the bactericidal effect of vancomycin. Released Li and vancomycin increased the mRNA or protein expressions of osteogenic markers of mesenchymal stem cells (MSCs). In vivo, the PLGA delivery systems were implanted into the distal femoral cavities of rabbits, and the cavity fluid content was aspirated and analyzed at each time point. The released Li and vancomycin lasted more than 6 weeks, and the vancomycin concentrations were much greater than the breakpoint sensitivity. Four rabbits in each group were sacrificed at 8 weeks for histological observation. More mature bone tissue was observed in the Li treatment group. This study provides a PLGA drug delivery system to meet the requirements of patients with bone infections.

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. Cite this article: Bone Joint Res 2023;12(8):504–511.

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.

Abstract Embedding multiple pharmaceutical drugs into poly(lactic‐co‐glycolic acid) (PLGA) nanofibers is known to improve the regeneration of the Achilles tendon upon implantation after injury and rapidly restore post‐surgery activity. In this study, an implantable material comprising celecoxib, collagen, bupivacaine, and PLGA (CCBP) is prepared by electrospinning. Its in vitro/vivo drug discharge behaviors are evaluated, and its efficacy in tendon regeneration is investigated in a rat model. The regeneration capacity of the wounded tendon is also compared with that of a doxycycline‐collagen‐bupivacaine‐PLGA (DCBP) combination. The results show that, relative to the primary PLGA nanofibers, the pharmaceutical‐embedded nanofibers have thinner fiber diameters and higher hydrophilicity. The drug‐eluting nanofibers also offer a sustained release of celecoxib for at least 30 d in vitro and 28 d in vivo. Achilles tendons regenerated using the CCBP combination nanofibers demonstrate a significantly higher maximum load‐to‐failure than normal tendons and those repaired using the DCBP combination. Additionally, the expression of growth factors and composition of collagen I induced by the CCBP combination are superior to those induced by the DCBP combination. The results suggest that the CCBP combination is a promising scaffold for the repair of ruptured Achilles tendons.

Despite the progress made in modern medical technology, the therapy of ruptured tendons continues to be a challenging task. We designed an amalgamated scaffold consisting of an additively manufactured polycaprolactone (PCL) tubular stent and electrospun collagen/drug-embedded poly-D-L-lactide-glycolide (PLGA) nanofibrous mats for the treatment of Achilles tendon rupture. The in vitro drug elution characteristics of pharmaceuticals from electrospun nanofibers was estimated. The in vivo efficacies of PCL stent/biomolecules-biomolecule-eluting nanofibers for the therapy of treatment of tendon rupture were also evaluated on in a rabbit model with histological examinations. The experimental results showed that the PCL stents with diamond pores exhibited the best mechanical properties. Drug-loaded PLGA nanofibers provided sustained discharges of vancomycin and ceftazidime for 40 days and lidocaine for over 10 days in vitro. The in vivo outcomes suggested that the repaired tendon strengths in the no-stent group and stent-only group (without drugs) showed poorer strength than the control (normal tendons with no surgery). Furthermore, the stent/drug group exhibited a higher recovery rate than the stent-only group. The integration of the additively manufactured PCL tubular stent and electrospun drug-eluting PLGA nanofibrous membranes can effectively enhance tendon treatment in a rabbit model.

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.

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.

MicroRNA (miRNA) 107 expression is downregulated but Wnt3a protein and β-catenin are upregulated in degenerated intervertebral disc (IVD). We investigated mir-107/Wnt3a-β-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 β-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 β-catenin in repaired cartilage tended to be lower in the HBO group. We observed that HBO inhibits Wnt3a/β-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.

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.

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.

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.

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-β1 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.

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.

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.

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.

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.

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.

Membrane systems offer a broad range of applications in the field of tissue engineering [...]

Stent implantation impairs local endothelial function and may be associated with subsequent adverse cardiovascular events. Telmisartan, an angiotensin II receptor blocker that has unique peroxisome proliferator-activated-receptor-gamma-mediated effects on cardiovascular disease, has been shown to enhance endothelial function and limit neointimal hyperplasia. This study utilized hybrid biodegradable/stent nanofibers to facilitate sustained and local delivery of telmisartan to injured arterial vessels. Telmisartan and poly(d,l)-lactide-co-glycolide (PLGA) (75:25) were dissolved in hexafluoroisopropyl alcohol and electrospun into biodegradable nanofibrous tubes which were coated onto metal stents. By releasing 20% of the loaded telmisartan in 30 days, these hybrid biodegradable/stent telmisartan-loaded nanofibers increased the migration of endothelial progenitor cells in vitro, promoted endothelialization, and reduced intimal hyperplasia. As such, this work provides insights into the use of PLGA nanofibers for treating patients with an increased risk of stent restenosis.

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.

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.

Abstract “Cable-tie” type biodegradable stents with drug-eluting nanofiber were developed to treat rabbit denuded arteries in this study. Biodegradable stents were fabricated using poly-L-lactide film following being cut and rolled into a cable-tie type stent. Additionally, drug-eluting biodegradable nanofiber tubes were electrospun from a solution containing poly (lactic-co-glycolic acid), rapamycin, and hexafluoroisopropanol, and then mounted onto the stents. The fabricated rapamycin-eluting cable-tie stents exhibited excellent mechanical properties on evaluation of compression test and collapse pressure, and less than 8% weight loss following being immersed in phosphate-buffered saline for 16 weeks. Furthermore, the biodegradable stents delivered high rapamycin concentrations for over 4 weeks and achieved substantial reductions in intimal hyperplasia associated with elevated heme oxygenase-1 and calponin level on the denuded rabbit arteries during 6 months of follow-up. The drug-eluting cable-tie type stents developed in this study might have high potential impacts for the local drug delivery to treat various vascular diseases.

Background: Malignant gliomas (MGs) are highly chemotherapy-resistant. Temozolomide (TMZ) and carmustine (BiCNU) are alkylating agents clinically used for treating MGs. However, their effectiveness is restrained by overexpression of the DNA repair protein O 6 -methylguanine-DNA methyltransferase (MGMT) in tumors. O 6 -benzylguanine (O 6 -BG) is a nonreversible inhibitor of MGMT, it promotes the cytotoxicity of alkylating chemotherapy. The authors have developed a hybrid-structured nanofibrous membrane (HSNM) that sequentially delivers high concentrations of O 6 -BG, BiCNU, and TMZ in an attempt to provide an alternative to the current therapeutic options for MGs. Methods: The HSNMs were implanted onto the cerebral surface of pathogen-free rats following surgical craniectomy, while the in vivo release behaviors of O 6 -BG, TMZ, and BiCNU from the HSNMs were explored. Subsequently, the HSNMs were surgically implanted onto the brain surface of two types of tumor-bearing rats. The survival rate, tumor volume, malignancy of tumor, and apoptotic cell death were evaluated and compared with other treatment regimens. Results: The biodegradable HSNMs sequentially and sustainably delivered high concentrations of O 6 -BG, BiCNU, and TMZ for more than 14 weeks. The tumor-bearing rats treated with HSNMs demonstrated therapeutic advantages in terms of retarded and restricted tumor growth, prolonged survival time, and attenuated malignancy. Conclusion: The results demonstrated that O 6 -BG potentiates the effects of interstitially transported BiCNU and TMZ. Therefore, O 6 -BG may be required for alkylating agents to offer maximum therapeutic benefits for the treatment of MGMT-expressing tumors. In addition, the HSNM-supported chemoprotective gene therapy enhanced chemotherapy tolerance and efficacy. It can, therefore, potentially provide an improved therapeutic alternative for MGs.

This paper describes the manufacture of binary nanostructured films utilizing nanosphere lithography and ultraviolet (UV) roller imprinting. To manufacture the binary nanofeatured template, polystyrene nanocolloids of two distinct dimensions (900 and 300 nm) were primarily self-assembly spun coated on a silicon substrate. A roller imprinting facility equipped with polydimethylsiloxane molds and ultraviolet radiation was employed. During the imprinting procedure, the roller was steered by a motor and compressed the ultraviolet-curable polymeric layer against the glass substrate, where the nanofeatured layer was cured by the UV light source. Binary nanofeatured films were thus obtained. The influence of distinct processing variables on the imprinting of nanofeatured films was investigated. The empirical data suggested that with appropriate processing conditions, binary nanofeatured plastic films can be satisfactorily manufactured. It also demonstrated that roller imprinting combined with ultraviolet radiation can offer an easy yet effective method to prepare binary nanofeatured films, with a miniatured processing time and enhanced part quality.

This paper reports the binary colloid assembly of nanospheres using spin coating techniques. Polystyrene spheres with sizes of 900 and 100 nm were assembled on top of silicon substrates utilizing a spin coater. Two different spin coating processes, namely concurrent and sequential coatings, were employed. For the concurrent spin coating, 900 and 100 nm colloidal nanospheres of latex were first mixed and then simultaneously spin coated onto the silicon substrate. On the other hand, the sequential coating process first created a monolayer of a 900 nm nanosphere array on the silicon substrate, followed by the spin coating of another layer of a 100 nm colloidal array on top of the 900 nm array. The influence of the processing parameters, including the type of surfactant, spin speed, and spin time, on the self-assembly of the binary colloidal array were explored. The empirical outcomes show that by employing the optimal processing conditions, binary colloidal arrays can be achieved by both the concurrent and sequential spin coating processes.

Polycaprolactone/nano-hydroxylapatite (PCL/nHA) nanocomposites have found use in tissue engineering and drug delivery owing to their good biocompatibility with these types of applications in addition to their mechanical characteristics. Three-dimensional (3D) printing of PCL/nHA nanocomposites persists as a defiance mostly because of the lack of commercial filaments for the conventional fused deposition modeling (FDM) method. In addition, as the composites are prepared using FDM for the purpose of delivering pharmaceuticals, thermal energy can destroy the embedded drugs and biomolecules. In this report, we investigated 3D printing of PCL/nHA using a lab-developed solution-extrusion printer, which consists of an extrusion feeder, a syringe with a dispensing nozzle, a collection table, and a command port. The effects of distinct printing variables on the mechanical properties of nanocomposites were investigated. Drug-eluting nanocomposite screws were also prepared using solution-extrusion 3D printing. The empirical outcomes suggest that the tensile properties of the 3D-printed PCL/nHA nanocomposites increased with the PCL/nHA-to-dichloromethane (DCM) ratio, fill density, and print orientation but decreased with an increase in the moving speed of the dispensing tip. Furthermore, printed drug-eluting PCL/nHA screws eluted high levels of antimicrobial vancomycin and ceftazidime over a 14-day period. Solution-extrusion 3D printing demonstrated excellent capabilities for fabricating drug-loaded implants for various medical applications.

We report the fabrication of nanofeatured polymeric films using nanosphere lithography and ultraviolet (UV) soft-mold roller embossing and show an illuminative example of their application to solar cells. To prepare the nanofeatured template, polystyrene nanocolloids of two distinct sizes (900 and 300 nm) were overlaid on silicon substrates using a spin coater. A lab-made soft-mold roller embossing device equipped with a UV light source was adopted. A casting method was employed to replicate the nanofeatured template onto polydimethylsiloxane, which was used as the soft mold. During the embossing procedure, the roller was driven by a step motor and compressed the UV-curable resin against the glass substrate to form the nanofeatured layer, which was subsequently cured by UV radiation. Polymer films with nanoscaled features were thus obtained. The influence of distinct processing variables on the reproducibility of the nanofeatured films was explored. The empirical outcomes demonstrate that UV soft-mold roller embossing offers a simple yet potent way of producing nanofeatured films.

Osteosynthesis surgery for rib fractures is controversial and challenging. This study developed a noval poly(ε-caprolactone) (PCL)-based biodegradable “cable-tie” fixator for osteosynthesis surgery for rib fractures. A biodegradable fixator specifically for fractured ribs was designed and fabricated by a micro-injection molding machine in our laboratory. The fixator has three belts that could be passed through matching holes individually. The locking mechanism allows the belt movement to move in only one direction. To examine the in vitro biomechanical performance, ribs 3–7 from four fresh New Zealand rabbits were employed. The load to failure and stress-strain curve was compared in the three-point bending test among native ribs, titanium plate-fixed ribs, and PCL fixator-fixed ribs. In the in vivo animal study, the sixth ribs of New Zealand rabbits were osteotomized and osteosynthesis surgery was performed using the PCL fixator. Outcomes were assessed by monthly X-ray examinations, a final micro-computed tomography (CT) scan, and histological analysis. The experimental results suggested that the ribs fixed with the PCL fixator were significantly less stiff than those fixed with titanium plates (p < 0.05). All ribs fixed with the PCL fixators exhibited union. The bridging callus was confirmed by gross, radiographic micro-three-dimensional (3D) CT, and histological examinations. In addition, there was no significant inflammatory response of the osteotomized ribs or the PCL-rib interface during application. The novel PCL fixator developed in this work achieves satisfactory results in osteosynthesis surgery for rib fractures, and may provide potential applications in other orthopedic surgeries.

Polycaprolactone (PCL) is a resorbable semicrystalline polymer that degrades slowly via hydrolysis and has applications in medical implants and drug delivery. As a result of its low melting point, PCL can be processed easily by conventional polymer processing techniques. However, the additive manufacturing of PCL remains a challenge, mainly due to the fact that there are no commercially available filaments for traditional fused deposition modeling (FDM). Furthermore, when the materials are fabricated via FDM for drug delivery applications, the high temperature may deactivate the incorporated drugs/biomolecules. This study investigates the solution extrusion additive manufacturing of PCL using a lab-developed solution-type device. The device comprises a solution extrusion feeder, driving stepper motors, a power source, a syringe equipped with a dispensing tip, an accumulation platform, and a control interface. The influences of different manufacturing parameters on part quality were evaluated. The experimental results suggest that the tensile strength of the additively manufactured parts increases with fill density but decreases with the ratio of PCL to dichloromethane (DCM) and moving speed of the dispensing tip. Parts fabricated by 90° print orientation of infill exhibited the greatest mechanical strength. The fabricated parts tend to heal the gaps among strips after additive manufacturing, but tiny pores can still be seen on the surfaces.

Malignant glioma (MG) is extremely aggressive and highly resistant to chemotherapeutic agents. Using electrospraying, the potent chemotherapeutic agent 7-ethyl-10-hydroxycamptothecia (SN-38) was embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs). The SMPs were stereotactically injected into the brain parenchyma of healthy rats and intratumorally injected into F98 glioma-bearing rats for estimating the pharmacodynamics and therapeutic efficacy. SN-38 was rapidly released after injection and its local (brain tissue) concentration remained much higher than that in the blood for more than 8 weeks. Glioma-bearing rats were divided into three groups—group A (n = 13; stereotactically injected pure PLGA microparticles), group B (n = 12; stereotactically injected Gliadel wafer and oral temozolomide), and group C (n = 13; stereotactic and intratumoral introduction of SMPs). The SMPs exhibited significant therapeutic efficacy, with prolonged survival, retarded tumor growth, and attenuated malignancy. The experimental results demonstrated that SMPs provide an effective and potential strategy for the treatment of MG.

In this study, we explored the release characteristics of analgesics, namely levobupivacaine, lidocaine, and acemetacin, from electrosprayed poly(D,L-lactide-co-glycolide) (PLGA) microparticles. The drug-loaded particles were prepared using electrospraying techniques and evaluated for their morphology, drug release kinetics, and pain relief activity. The morphology of the produced microparticles elucidated by scanning electron microscopy revealed that the optimal parameters for electrospraying were 9 kV, 1 mL/h, and 10 cm for voltage, flow rate, and travel distance, respectively. Fourier-transform infrared spectrometry indicated that the analgesics had been successfully incorporated into the PLGA microparticles. The analgesic-loaded microparticles possessed low toxicity against human fibroblasts and were able to sustainably elute levobupivacaine, lidocaine, and acemetacin in vitro. Furthermore, electrosprayed microparticles were found to release high levels of lidocaine and acemetacin (well over the minimum therapeutic concentrations) and levobupivacaine at the fracture site of rats for more than 28 days and 12 days, respectively. Analgesic-loaded microparticles demonstrated their effectiveness and sustained performance for pain relief in fracture injuries.

Three-dimensional (3D) printing is a simple and versatile process for producing parts of complex geometries. Although the process possesses several manufacturing advantages, such as rapid prototyping, customization, and complexity, the optimization of the 3D printing procedure remains a challenge. Here we explore the influences of various processing conditions on the mechanical properties of melt extrusion- and solution extrusion-printed polylactide (PLA) products by adopting a robust experimental design model. In addition to the commercially available melt extrusion 3D printer, a novel solution-type 3D printer has been exploited especially for this study, which consists of a solution-type plunger-actuated feeding system, stepper motors and motion components, a power supply unit, a print bed, a user interface, and connectivity. The effects of various parameters were investigated by adopting a robust experimental design. We compared the parts printed using the melt extrusion and solution extrusion methods and found that, in the melt extrusion printing, the print speed and fill density were the principal parameters affecting product quality, while in the solution extrusion printing, oven temperature, fill density, and PLA/dichloromethane (DCM) ratio were the key parameters. By scanning electron microscopy, we found that the melt extrusion-printed parts exhibit a strip-like microstructure and the solution extrusion-printed parts show a fused surface morphology. Due to the addition of solvent, the solution-printed PLA material show a different thermal profile in the differential scanning calorimeter analysis, which in turn affects the mechanical behaviour of printed parts.

Brain abscesses are emergent and life-threating despite advances in modern neurosurgical techniques and antibiotics. The present study explores the efficacy of vancomycin embedded to 50:50 poly(lactic-co-glycolide acid) (PLGA) microparticles in the treatment of brain abscess. The vancomycin embedded microparticles (VMPs) were stereotactically introduced into the cerebral parenchyma in Staphylococcus aureus bacteria- induced brain abscess-bearing rats. Experimental rats were divided into three groups: group A (n = 13; no treatment), group B (n = 14; daily vancomycin injection (5 mg intraperitoneally), and group C (n = 12; stereotactic introduction of VMPs into the abscess cavity). Group C exhibited no inflammatory response and significantly increased survival and reduced mean abscess volumes (p

Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l)-lactide-co-glycolide] (PLGA) was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm) and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release) and reached completion around day 28. Scanning electron microscope (SEM) photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered). In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

Fungal osteomyelitis has been difficult to treat, with first-line treatments consisting of implant excision, radical debridement, and local release of high-dose antifungal agents. Locally impregnated antifungal beads are another popular treatment option. This study aimed to develop biodegradable antifungal-agent-loaded Poly(d,l-lactide-co-glycolide) (PLGA) beads and evaluate the in vitro/in vivo release patterns of amphotericin B and fluconazole from the beads. Beads of different sizes were formed using a compression-molding method, and their morphology was evaluated via scanning electron microscopy. Intrabead incorporation of antifungal agents was evaluated via Fourier-transform infrared spectroscopy, and in vitro fluconazole liberation curves of PLGA beads were inspected via high-performance liquid chromatography. When we implanted the drug-incorporated beads into the bone cavity of rabbits, we found that a high level of fluconazole (beyond the minimum therapeutic concentration [MTC]) was released for more than 49 d in vivo. Our results indicate that compression-molded PLGA/fluconazole beads have potential applications in treating bone infections.

Electrospraying has been recognized as an important technique for the production of microparticles for pharmaceutical applications. Nevertheless, the produce of poly (d,l)-lactide-co-glycolide (PLGA) microspheres with a desired size distribution remains a challenge. We conducted an empirical study, based on a fractional orthogonal design, to optimize the size distribution of electrosprayed particles. The influence of different processing factors, including PLGA concentration in the solution, volumetric flow rate of the solution, travel distance between the needle tip and the collection, voltage applied to the polymer solution, size of the needle, and type of solvent on the electrospraying of polymeric microparticles was investigated. After electrospraying, the size distribution of the PLGA particles was characterized and analyzed. Among the selected factors, the type of solvent used was the principal factor affecting the particle size of electrosprayed microspheres. Hexafluoro-2-propanol (HFIP) electrosprayed microparticles with the smallest diameter. However, hollowed particles could be seen among these microspheres. Dichloromethane (DCM) was found to electrospray microspheres with a fairly spherical geometry, while trichloromethane (TCM) electrosprayed particles with relatively rougher surfaces. Finally, the particle size of sprayed microspheres decreases somewhat with the polymer concentration and travel distance.

In this study, we developed biodegradable lidocaine–/vancomycin–/ceftazidime–eluting poly(d,l–lactide–co–glycolide) (PLGA) nano/microparticulate carriers using an electrospraying process, and we evaluated the release behaviors of the carriers in knee joints. To prepare the particles, predetermined weight percentages of PLGA, vancomycin, ceftazidime, and lidocaine were dissolved in solvents. The PLGA/antibiotic/lidocaine solutions were then fed into a syringe for electrospraying. After electrospraying, the morphology of the sprayed nano/microparticles was elucidated by scanning electron microscopy (SEM). The in vitro antibiotic/analgesic release characteristics of the nano/microparticles were studied using high-performance liquid chromatography (HPLC). In addition, drug release to the synovial tissues and fluids was studied in vivo by injecting drug-loaded nano/microparticles into the knee joints of rabbits. The biodegradable electrosprayed nano/microparticles released high concentrations of vancomycin/ceftazidime (well above the minimum inhibition concentration) and lidocaine into the knee joints for more than 2 weeks and for over 3 days, respectively. Such results suggest that electrosprayed biodegradable nano/microcarriers could be used for the long-term local delivery of various pharmaceuticals.

This study developed multi-layered lidocaine- and epinephrine-eluting biodegradable poly[(d,l)-lactide-co-glyco lide] (PLGA)/collagen nanofibers. An electrospinning technique was employed to fabricate the multi-layer biodegradable drug-eluting nanofibers. After fabrication, the nanofibrous membranes were characterized. The drug release characteristics were also investigated. In addition, the in vivo efficacy of nanofibers for pain relief and hemostasis in palatal oral wounds of rabbits were evaluated. Histological examinations were also completed. The experimental results suggested that all nanofibers exhibited good biocompatibility and eluted effective levels of lidocaine and epinephrine at the initial stages of wound recovery.

This study aimed to develop a new biodegradable polymeric cage to convert corticocancellous bone chips into a structured strut graft for treating segmental bone defects. A total of 24 adult New Zealand white rabbits underwent a left femoral segmental bone defect creation. Twelve rabbits in group A underwent three-dimensional (3D) printed cage insertion, corticocancellous chips implantation, and Kirschner-wire (K-wire) fixation, while the other 12 rabbits in group B received bone chips implantation and K-wire fixation only. All rabbits received a one-week activity assessment and the initial image study at postoperative 1 week. The final image study was repeated at postoperative 12 or 24 weeks before the rabbit scarification procedure on schedule. After the animals were sacrificed, both femurs of all the rabbits were prepared for leg length ratios and 3-point bending tests. The rabbits in group A showed an increase of activities during the first week postoperatively and decreased anterior cortical disruptions in the postoperative image assessments. Additionally, higher leg length ratios and 3-point bending strengths demonstrated improved final bony ingrowths within the bone defects for rabbits in group A. In conclusion, through this bone graft converting technique, orthopedic surgeons can treat segmental bone defects by using bone chips but with imitate characters of structured cortical bone graft.