The role of a drug-loaded poly (lactic co-glycolic acid) (PLGA) copolymer stent in the treatment of ovarian cancer.

Objectives: Cisplatin (CDDP) is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors, including ovarian cancer. However, adverse side effects and acquired drug resistance are observed in the clinical application of CDDP. Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem. Methods: In this study, 3D printing technology was used to prepare a CDDP-poly (lactic-co-glycolic acid) (CDDP-PLGA) polymer compound stent, and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo. Results: The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice, whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection. Compared with the control group, CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein (P < 0.01; P < 0.01) and decreased vascular endothelial growth factor mRNA (P < 0.05) and protein levels (P < 0.01), however, CDDP-PLGA significantly decreased the mRNA and protein levels of p-glycoprotein (P < 0.01; P < 0.01) and vascular endothelial growth factor (P < 0.01; P < 0.01), which are associated with chemoresistance, in subcutaneous tumor tissue. Immunohistochemistry assay results revealed that, in the CDDP-PLGA group, the staining of the proliferation-related genes Ki67 and PCNA were lightly, and the apoptosis-related gene caspase-3 stained deeply. Conclusions: PLGA biomaterials loaded with CDDP, as compared with the same amount of free CDDP, showed good efficacy in terms of cytotoxicity, as evidenced by changes in apoptosis. Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis, and improve the therapeutic effect. This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.

E-jet 3D printed drug delivery implants to inhibit growth and metastasis of orthotopic breast cancer.

Drug-loaded implants have attracted considerable attention in cancer treatment due to their precise delivery of drugs into cancer tissues. Contrary to injected drug delivery, the application of drug-loaded implants remains underutilized given the requirement for a surgical operation. Nevertheless, drug-loaded implants have several advantages, including a reduction in frequency of drug administration, minimal systemic toxicity, and increased delivery efficacy. Herein, we developed a new, precise, drug delivery device for orthotopic breast cancer therapy able to suppress breast tumor growth and reduce pulmonary metastasis using combination chemotherapy. Poly-lactic-co-glycolic acid scaffolds were fabricated by 3D printing to immobilize 5-fluorouracil and NVP-BEZ235. The implantable scaffolds significantly reduced the required drug dosages and ensured curative drug levels near tumor sites for prolonged period, while drug exposure to normal tissues was minimized. Moreover, long-term drug release was achieved, potentially allowing one-off implantation and, thus, a major reduction in the frequency of drug administration. This drug-loaded scaffold has great potential in anti-tumor treatment, possibly paving the way for precise, effective, and harmless cancer therapy.

E-Jet 3D-Printed Scaffolds as Sustained Multi-Drug Delivery Vehicles in Breast Cancer Therapy.

PURPOSE: Combination chemotherapy is gradually receiving more attention because of its potential synergistic effect and reduced drug doses in clinical application. However, how to precisely control drug release dose and time using vehicles remains a challenge. This work developed an efficient drug delivery system to combat breast cancer, which can enhance drug effects despite reducing its concentration. METHODS: Controlled-release poly-lactic-co-glycolic acid (PLGA) scaffolds were fabricated by E-jet 3D printing to deliver doxorubicin (DOX) and cisplatin (CDDP) simultaneously. RESULTS: This drug delivery system allowed the use of a reduced drug dosage resulting in a better effect on the human breast cancer cell apoptosis and inhibiting tumor growth, compared with the effect of each drug and the two drugs administrated without PLGA scaffolds. Our study suggested that DOX-CDDP-PLGA scaffolds could efficiently destroy MDA-MB-231 cells and restrain tumor growth. CONCLUSIONS: The 3D printed PLGA scaffolds with their time-programmed drug release might be useful as a new multi-drug delivery vehicle in cancer therapy, which has a potential advantage in a long term tumor cure and prevention of tumor recurrence.

Enhanced growth and differentiation of myoblast cells grown on E-jet 3D printed platforms.

BACKGROUND: Skeletal muscle tissue engineering often involves the prefabrication of muscle tissues in vitro by differentiation and maturation of muscle precursor cells on a platform which provides an environment that facilitates the myogenic differentiation of the seeded cells. METHODS: Poly lactic-co-glycolic acid (PLGA) 3D printed scaffolds, which simulate the highly complex structure of extracellular matrix (ECM), were fabricated by E-jet 3D printing in this study. The scaffolds were used as platforms, providing environment that aids in growth, differentiation and other properties of C2C12 myoblast cells. RESULTS: The C2C12 myoblast cells grown on the PLGA 3D printed platforms had enhanced cell adhesion and proliferation. Moreover, the platforms were able to induce myogenic differentiation of the myoblast cells by promoting the formation of myotubes and up-regulating the expressions of myogenic genes (MyHC and MyOG). CONCLUSION: The fabricated 3D printed platforms have excellent biocompatibility, thereby can potentially be used as functional cell culture platforms in skeletal tissue engineering and regeneration.

Collagen synthesis modulated in wounds treated by pulsed radiofrequency energy.

BACKGROUND: Chronic wounds are biochemically complex and are associated with insufficient cell proliferation, angiogenesis, and extracellular matrix remodeling. The mechanisms by which pulsed radiofrequency energy modulates wound healing are still unclear. METHODS: Db/db mice were wounded and exposed to pulsed radiofrequency energy. Gross closure, cell proliferation, and morphometric analysis of CD31-stained wound cross-sections were assessed. The mRNA expression of profibrotic factors (transforming growth factor-ß and platelet-derived growth factor-A), angiogenetic factors (vascular endothelial growth factor and basic fibroblast growth factor), and extracellular matrix components (collagen I and α-smooth muscle actin) were evaluated by quantitative reverse-transcriptase polymerase chain reaction. Collagen protein level of the wound was determined by Western blot analysis. To test the effect of pulsed radiofrequency energy on cell movement in wound healing, cell migration was monitored in monolayer dermal fibroblast cultures. The degree of collagen alignment and gelation time was quantitatively assessed using image analysis techniques. RESULTS: Pulsed radiofrequency energy-treated wounds were characterized by dermal cell proliferation and increased collagen synthesis. By contrast, the CD31 density and the mRNA expression of vascular endothelial growth factor and basic fibroblast growth factor showed no significant difference between the pulsed radiofrequency energy-treated wounds and the sham group. The pulsed radiofrequency energy-treated dermal fibroblast cultures expressed a significantly longer gelation time compared with the sham-exposed cultures. CONCLUSIONS: Exposing wounds to pulsed radiofrequency accelerated wound healing in this diabetic mouse model by means of significantly increasing dermal cell proliferation and collagen synthesis. A cellular mechanism behind these observations has been proposed.