Browsing by Author "Ferreira, Paula"
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- Alginate based scaffolds for bone tissue engineeringPublication . Valente, Joana; Valente, Tiago António Martins; Alves, Patrícia; Ferreira, Paula; Silva, Abílio; Correia, I.J.The design and production of scaffolds for bone tissue regeneration is yet unable to completely reproduce the native bone properties. In the present study new alginate microparticle and microfiber aggregated scaffolds were produced to be applied in this area of regenerative medicine. The scaffolds' mechanical properties were characterized by thermo mechanical assays. Their morphological characteristics were evaluated by isothermal nitrogen adsorption and scanning electron microscopy. The density of both types of scaffolds was determined by helium pycnometry and mercury intrusion porosimetry. Furthermore, scaffolds' cytotoxic profiles were evaluated in vitro by seeding human osteoblast cells in their presence. The results obtained showed that scaffolds have good mechanical and morphological properties compatible with their application as bone substitutes. Moreover, scaffold's biocompatibility was confirmed by the observation of cell adhesion and proliferation after 5 days of being seeded in their presence and by non-radioactive assays.
- An overview of electrospun membranes loaded with bioactive molecules for improving the wound healing processPublication . Miguel, Sónia; Sequeira, Rosa; Moreira, André; Cabral, C.S.D.; Mendonça, António; Ferreira, Paula; Correia, I.J.Nowadays, despite the intensive research performed in the area of skin tissue engineering, the treatment of skin lesions remains a big challenge for healthcare professionals. In fact, none of the wound dressings currently used in the clinic is capable of re-establishing all the native features of skin. An ideal wound dressing must confer protection to the wound from external microorganisms, chemical, and physical aggressions, as well as promote the healing process by stimulating the cell adhesion, differentiation, and proliferation. In recent years different types of wound dressings (such as films, hydrocolloids, hydrogels, micro/nano fibers) have been developed. Among them, electrospun nanofibrous membranes due to their intrinsic properties like high surface area-to-volume ratio, porosity and structural similarity with the skin extracellular matrix have been regarded as highly promising for wound dressings applications. Additionally, the nanofibers available in these membranes can act as drug delivery systems, which prompted the incorporation of biomolecules within their structure to prevent skin infections as well as improve the healing process. In this review, examples of different bioactive molecules that have been loaded on polymeric nanofibers are presented, highlighting the antibacterial biomolecules (e.g. antibiotics, silver nanoparticles and natural extracts-derived products) and the molecules capable of enhancing the healing process (e.g. growth factors, vitamins, and anti-inflammatory molecules).
- Coaxial electrospun PCL/Gelatin-MA fibers as scaffolds for vascular tissue engineeringPublication . Coimbra, Patrícia; Santos, Patrícia; Alves, Patrícia; Miguel, Sónia P.; Carvalho, Marco António Paulo de; Sá, Kevin; Correia, Ilídio Joaquim Sobreira; Ferreira, PaulaCoaxial electrospinning is a technique that allows the production of nanofibers with a core–shell structure. Such fibers present several advantages as materials for the preparation of scaffolds, namely due to the possibility of combining a core with the desired mechanical properties with a shell prepared from biocompatible materials that will establish proper interactions with the host. Herein, core-shell fibrous meshes, composed of a polycaprolactone (PCL) core and a functionalized gelatin shell, were prepared by coaxial electrospinning and then photocrosslinked under UV light aiming to be used in vascular tissue regeneration. The suitability of the meshes for the pretended biomedical application was evaluated by assessing their chemical/physical properties as well as their haemo and biocompatibility in vitro. The obtained results revealed that meshes’ shell prepared with a higher content of gelatin showed fibers with diameters presenting a unimodal distribution and a mean value of 600 nm. Moreover, those fibers with higher content of gelatin also displayed lower water contact angles, and therefore higher hydrophilicities. Such features are crucial for the good biologic performance displayed by these meshes, when in contact with blood and with Normal Human Dermal Fibroblasts cells.
- Combinatorial delivery of doxorubicin and acridine orange by gold core silica shell nanospheres functionalized with poly(ethylene glycol) and 4- methoxybenzamide for cancer targeted therapyPublication . Guimarães, Rafaela; Rodrigues, Ana Carolina Félix; Fernandes, Natanael; Diogo, Duarte de Melo; Ferreira, Paula; Correia, I.J.; Moreira, André F.Combinatorial therapies based on the simultaneous administration of multiple drugs can lead to synergistic effects, increasing the efficacy of the cancer therapy. However, it is crucial to develop new delivery systems that can increase the drugs' therapeutic selectivity and efficacy. Gold core silica shell (AuMSS) nanoparticles present physicochemical properties that allow their simultaneous application as drug delivery and imaging agents. Herein, poly(ethylene glycol) was modified with 4-methoxybenzamide and 3- (triethoxysilyl)propyl isocyanate (TPANIS) to create a novel surface functionalization capable of improving the colloidal stability and specificity of AuMSS nanospheres towards cancer cells. Moreover, a dual drug combination based on Doxorubicin (DOX) and Acridine orange (AO) was characterized and administered using the AuMSS-TPANIS nanospheres. The obtained results show that the DOX:AO drug combination can mediate a synergistic therapeutic effect in both HeLa and MCF-7 cells, particularly at the 2:1, 1:1, and 1:2 ratios. Otherwise, the TPANIS functionalization increased the AuMSS nanospheres colloidal stability and selectivity towards MCF-7 cancer cells (overexpressing sigma receptors). Such also resulted in an enhanced cytotoxic effect against MCF-7 cells when administering the DOX:AO drug combination with the AuMSSTPANIS nanospheres. Overall, the obtained results confirm the therapeutic potential of the DOX:AO drug combination as well as the targeting capacity of AuMSS-TPANIS, supporting its application in the cancer targeted combinatorial chemotherapy.
- Development of a poly(vinyl alcohol)/lysine electrospun membrane-based drug delivery system for improved skin regenerationPublication . Sequeira, Rosa Maria Saraiva; Miguel, Sónia; Cabral, Cátia S. D.; Moreira, André; Ferreira, Paula; Correia, I.J.Nanofiber-based wound dressings are currently being explored as delivery systems of different biomolecules for avoiding skin infections as well as improve/accelerate the healing process. In the present work, a nanofibrous membrane composed of poly(vinyl alcohol) (PVA) and lysine (Lys) was produced by using the electrospinning technique. Further, anti-inflammatory (ibuprofen (IBP)) and antibacterial (lavender oil (LO)) agents were incorporated within the electrospun membrane through blend electrospinning and surface physical adsorption methods, respectively. The obtained results demonstrated that the PVA_Lys electrospun membranes incorporating IBP or LO displayed the suitable morphological, mechanical and biological properties for enhancing the wound healing process. Moreover, the controlled and sustained release profile attained for IBP was appropriate for the duration of the wound healing inflammatory phase, whereas the initial burst release of LO is crucial to prevent wound bacterial contamination. Indeed, the PVA_Lys_LO electrospun membranes were able to mediate a strong antibacterial activity against both S. aureus and P. aeruginosa, without compromising human fibroblasts viability. Overall, the gathered data emphasizes the potential of the PVA_Lys electrospun membranes-based drug delivery systems to be used as wound dressings.
- Development of gold-core silica shell nanospheres coated with poly-2-ethyl-oxazoline and β-cyclodextrin aimed for cancer therapyPublication . Reis, Ana Catarina Almeida; Rodrigues, Ana Carolina Félix; Moreira, André; Jacinto, Telma A.; Ferreira, Paula; Correia, I.J.Cancer is one of the major world public health problems and the currently available treatments are nonspecific and ineffective. This reality highlights the importance of developing novel therapeutic approaches. In this field, multifunctional nanomedicines have the potential to revolutionize the currently available treatments. These unique nanodevices can simultaneously act as therapeutic and imaging agents allowing the real-time monitoring of the nanoparticles biodistribution and the treatment outcome. Among the different nanoparticles, the gold-core silica shell (AuMSS) nanoparticles advantageous physicochemical and biological properties make them promising nanoplatforms for cancer therapy. Nevertheless, their successful application as an effective cancer nanomedicine is limited by the unfavorable pharmacokinetics and uncontrolled release of the therapeutic payloads. Herein, a new polymeric coating for AuMSS nanospheres was developed by combining different ratios (25/75, 50/50 and 75/25) of two materials, Poly-2-ethyl-2-oxazoline (PEOZ) and β-cyclodextrin (β-CD). The surface functionalization of AuMSS nanospheres led to a size increase and to the neutralization of the surface charge. On the other side, the nanoparticles biological performance was improved. The coated AuMSS nanospheres showed an increased cytocompatibility and internalization rate by the HeLa cancer cells. Overall, the obtained data confirm the successful modification of the AuMSS nanospheres with PEOZ and β-CD as well as their promising properties for being applied in cancer therapy.
- Development of poly-2-ethyl-2-oxazoline coated gold-core silica shell nanorods for cancer chemo-photothermal therapyPublication . Moreira, André; Rodrigues, Ana Carolina Félix; Reis, Ana Catarina Almeida; Costa, Elisabete C.; Ferreira, Paula; Correia, Ilídio Joaquim SobreiraAim: Develop a new poly-2-ethyl-2-oxazoline (PEOZ)-based coating for doxorubicin-loaded gold-core mesoporous silica shell (AuMSS) nanorods application in cancer chemo-photothermal therapy. Methods: PEOZ functionalized AuMSS nanorods were obtained through the chemical grafting on AuMSS of a PEOZ silane derivative. Results: The PEOZ chemical grafting on the surface of AuMSS nanorods allowed the neutralization of nanodevices’ surface charge, from -30 to -15 mV, which improved nanoparticles’ biocompatibility, namely by decreasing the blood hemolysis to negligible levels. In vitro antitumoral studies revealed that the combined treatment mediated by the PEOZ-coated AuMSS nanorods result in a synergistic effect, allowing the complete eradication of cervical cancer cells. Conclusion: The application of the PEOZ coating improves the AuMSS nanorods performance as a multifunctional combinatorial therapy for cervical cancer.
- Development of UV cross-linked gelatin coated electrospun poly(caprolactone) fibrous scaffolds for tissue engineeringPublication . Correia, Tiago R.; Ferreira, Paula; Vaz, Rita; Alves, Patrícia; Figueiredo, Margarida; Correia, Ilídio Joaquim Sobreira; Coimbra, PatríciaCardiovascular disease is the leading cause of morbidity and mortality among industrialized countries. Vascular grafts are often required for the surgical treatments. Considering the limitations associated with the use of autografts and with the currently available synthetic materials, a growing demand in tissue engineered vascular grafts has been registered. During the work here described, electrospinning technique was used to prepared fibrous matrices to be applied as vascular implants. For that purpose, electrospun polycaprolactone (PCL) fibrous mats were produced and afterwards coated with different hydrogel formulations based in photocrosslinkable gelatin (GelMA) and the macromers poly(ethylene glycol) acrylate (PEGA) and poly(ethylene glycol) diacrylate (PEGDA). These were further photocrosslinked under UV irradiation using Irgacure® 2959 (by BASF) as the photoinitiator. The suitability of the coated scaffolds for the intended application, was evaluated by assessing their chemical/physical properties as well as their interaction with blood and endothelial cells.
- Dextran-Based Injectable Hydrogel Composites for Bone RegenerationPublication . Alves, Patrícia; Simão, Ana Filipa; Graça, Mariana F. P.; Mariz, Marcos; Correia, I.J.; Ferreira, PaulaCurrently, bone infections caused by diseases or injuries are a major health issue. In addition, the conventional therapeutic approaches used to treat bone diseases or injuries present several drawbacks. In the area of tissue engineering, researchers have been developing new alternative therapeutic approaches, such as scaffolds, to promote the regeneration of injured tissues. Despite the advantages of these materials, most of them require an invasive surgical procedure. To overcome these problems, the main focus of this work was to develop scaffolds for bone regeneration, which can be applied using injectable hydrogels that circumvent the use of invasive procedures, while allowing for bone regeneration. Throughout this work, injectable hydrogels were developed based on a natural polymer, dextran, along with the use of two inorganic compounds, calcium β-triphosphate and nanohydroxyapatite, that aimed to reinforce the mechanical properties of the 3D mesh. The materials were chemically characterized considering the requirements for the intended application: the swelling capacity was evaluated, the degradation rate in a simulated physiological environment was assessed, and compression tests were performed. Furthermore, vancomycin was incorporated into the polymeric matrices to obtain scaffolds with antibacterial performance, and their drug release profile was assessed. The cytotoxic profile of the hydrogels was assessed by an MTS assay, using osteoblasts as model cells. The data obtained demonstrated that dextran-based hydrogels were successfully synthesized, with a drug release profile with an initial burst between 50 and 80% of the drug. The hydrogels possess fair biocompatibility. The swelling capacity showed that the stability of the samples and their degradation profile is compatible with the average time period required for bone regeneration (usually about one month) and have a favorable Young’s modulus (200–300 kPa). The obtained hydrogels are well-suited for bone regeneration applications such as infections that occur during implantation or bone graft substitutes with antibiotics.
- Electrospun polymeric nanofibres as wound dressings: A reviewPublication . Miguel, Sónia P.; Figueira, Daniela Sofia Rodrigues; Simões, Déborah; Ribeiro, MP.; Coutinho, Paula; Ferreira, Paula; Correia, Ilídio Joaquim SobreiraSkin wounds have significant morbidity and mortality rates associated. This is explained by the limited effectiveness of the currently available treatments, which in some cases do not allow the reestablishment of the structure and functions of the damaged skin, leading to wound infection and dehydration. These drawbacks may have an impact on the healing process and ultimately prompt patients’ death. For this reason, researchers are currently developing new wound dressings that enhance skin regeneration. Among them, electrospun polymeric nanofibres have been regarded as promising tools for improving skin regeneration due to their structural similarity with the extracellular matrix of normal skin, capacity to promote cell growth and proliferation and bactericidal activity as well as suitability to deliver bioactive molecules to the wound site. In this review, an overview of the recent studies concerning the production and evaluation of electrospun polymeric nanofibrous membranes for skin regenerative purposes is provided. Moreover, the current challenges and future perspectives of electrospun nanofibrous membranes suitable for this biomedical application are highlighted.