Browsing by Author "Santos, C."
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- Characterization of a novel 3D-polymeric scaffold as a co-delivery systemPublication . Zegre, Miguel; Silveira, M.; Anjos, I.; Ribeiro, I. A.; Santos, C.; Caetano, Liliana Aranha; Gonçalves, L.; Bettercourt, A.Osteomyelitis is an inflammation of the bone caused by infection, leading to necrosis and tissue destruction. It can cause persistent morbidity and become a chronic disease, being one of the infectious diseases most difficult to manage. Staphylococcus aureus is the most usual causative pathogen in osteomyelitis, and bacterial infections are often complicated by concomitant fungal infections, Candida sp. being the most common. Co-encapsulation of drugs provides a convenient means for the administration of multiple drugs directed at commonly associated diseases. Three-dimensional scaffolds have become a crucial element of bone tissue engineering and regenerative medicine, are designed to provide an ideal environment for bone formation. Thus, this work aims to develop a new local drug-delivery system for the modulation of polymicrobial activity in bone infections, through the co-delivery of minocycline and voriconazole to the local site of infection, while fostering bone repair.
- Co-delivery of antimicrobials based on poly(D,L-lactic acid) 3D-scaffoldsPublication . Zegre, Miguel; Falcão, M.; Ribeiro, I. A.; Santos, C.; Barros, J.; Monteiro, F. J.; Ferraz, M. P.; Caetano, Liliana Aranha; Gonçalves, L.; Bettencourt, A.Bone infection treatment is a clinical challenge, often complicated by simultaneous polymicrobial infections. A growing number of studies address the co-isolation of fungal and bacterial species, such as Candida albicans and Staphylococcus aureus, from polymicrobial biofilm associated with osteomyelitis. Recent publications demonstrate that scaffolds with local drug delivery ability, display high antimicrobial efficiency rates and reduced toxicity, suppressing the progression of bone disease and decreasing the number of pathogens in mono- or polymicrobial-biofilms.
- Evaluation of a dual function minocycline polymeric bone scaffoldPublication . Anjos, I.; Zegre, Miguel; Santos, C.; Alves, M. M.; Ribeiro, I.; Gonçalves, L.; Bettencourt, A. F.It is estimated that orthopedic procedures will rise due to population growth along with aging and increasing chronic diseases. Consequently, orthopedic infections associated with these procedures can be a serious complication, leading to a state of morbidity. Current strategies for treating bone infections and defects present several limitations, namely low local concentrations and systemic toxicity. To overcome these limitations, synthetic and biocompatible bone grafts substitutes (scaffolds) are being developed as platforms for local drug delivery, a strategy that allows high antibiotics concentration in bone for orthopedic infections treatment. Thus, this work aims to develop a drug delivery system with osteoconductive and osteoinductive properties for bone regeneration and capable of treating the infection. For this purpose, porous PDLLA scaffolds were produced by the solvent casting technique, functionalized with bioglass (BG) and collagen (Col), and loaded with 0.5, 0.25, 0.1, or 0.05 mg/mL of minocycline hydrochloride (MH), a dual function drug that beyond its antibiotic role, also induce osteoblastic cells differentiation. Scaffolds’ surface morphology was characterized by scanning electron microscopy (SEM) and elemental chemical composition was performed by X-ray energy dispersive spectrometer (EDS). These drug delivery systems were also characterized in terms of drug release profiles and cytocompatibility through in vitro studies. SEM analysis demonstrated a porous surface and confirmed the functionalization. Regarding drug release profiles, the obtained results suggest a two-phase stage release, with an initial burst release of approximately 60%, 30%, and 10% of MH in the first 15 min, for the two most MH concentrated groups, 0.1 mg/mL of MH group and 0.05 mg/mL of MH group, respectively, followed by a sustained release. In vitro cell studies were promising for scaffolds adsorbed with 0.1 and 0.05 mg/mL of MH, not revealing cytotoxicity, contrary to what was seen for scaffolds with higher concentrations of MH (0.5 and 0.25 mg/mL).In conclusion, due to release profiles of the drug and in vitro cell assays, scaffolds adsorbed with the two lowest MH concentrations seem a promising strategy for acute infection treatment, however, antimicrobial assays must be conducted.
- Handgrip dynamometry and patient-generated subjective global in patients with non-resectable lung cancerPublication . Barata, A. T.; Santos, C.; Cravo, M.; Vinhas, M. D. C.; Morais, C.; Carolino, Elisabete; Vieira, J. Roldão; Fonseca, J.Rationale: Undernutrition is frequently associated with advanced lung cancer. Accurate nutritional assessment tools are important to provide the proper nutritional therapy. Hand grip strength (HGS) has already been used in these patients and the findings suggest it is a good indicator of nutritional status. The aim of this study was to evaluate the association between nutritional status and hand grip strength in patients with nonresectable lung cancer.
- Poly(D,L-lactic acid) scaffolds as an innovative approach to the treatment of mixed S. aureus-C. albicans biofilmsPublication . Zegre, Miguel; Barros, J.; Ribeiro, I. A.; Santos, C.; Aranha Caetano, Liliana; Gonçalves, L.; Monteiro, F.; Ferraz, M.; Bettencourt, A.Introduction: The treatment of bacterial joint and bone infections in patients after multiple revision arthroplasties is very challenging. An expanding number of studies report the co-isolation of fungal and bacterial species (such as Candida albicans and Staphylococcus aureus) from polymicrobial biofilm associated with infections related to bone infections. Current investigations establish that local-specific drug delivery scaffolds with low toxicity and increased efficiency to specific sites when compared to oral and systemic administration approaches, can considerably lower the number of viable microorganisms in polymicrobial biofilms, preventing simultaneously the progression of infection in bone disorder. Notably, the development of co-delivery systems of at least two antimicrobials is yet a neglected approach, while it may be a critical strategy for the treatment of infections associated with polymicrobial biofilms. Simultaneously, it is recommended to assess the contribution of each microbial population within the biofilm to select the best therapy to treat polymicrobial infections. Among different biomaterials used in scaffolds as drug-delivery carriers, poly(lactic acid) (PLA) based polymers are being widely studied due to their versatility, low toxicity, and tailored biodegradability having the US Food and Drug Administration approval for clinical use. The adequate osteoconductive and anti-S. aureus effects of a collagen functionalized poly(D, L-lactic acid) (PDLLA) porous scaffold loaded with minocycline (a tetracycline antibiotic) have been previously demonstrated3. In the present study, we focus on the problem of mixed bacterial-fungal biofilm infections and the joining of two antimicrobials in the PDLLA scaffold. Minocycline and voriconazole (an antifungal triazole) were the chosen model drugs, since minocycline may represent a promising drug that can be administered in combination with azoles (namely voriconazole) to treat infections caused by pathogenic Candida species. Morphological and chemical properties of the co-delivery PDLLA scaffolds, as well as drug release profiles, were examined. The antibiofilm activity of these drug delivery systems was tested against single- and dual-species biofilms of S. aureus and C. albicans. The formation of dual-species S. aureus – C. albicans biofilms was studied over time to understand the relationship between both microorganisms during in vitro biofilm formation. Cytocompatibility and osteoconductive tests were also conducted using MG-63 osteoblasts to assess the biocompatibility of the PDLLA scaffolds.
- Poly(D,L-lactic acid) scaffolds as an innovative approach to the treatment of mixed S. aureus-C. albicans biofilmsPublication . Zegre, Miguel; Barros, J.; Ribeiro, I. A.; Santos, C.; Aranha Caetano, Liliana; Gonçalves, L.; Monteiro, F.; Ferraz, M.; Bettencourt, A.Problem - Bone infections associated with polymicrobial biofilm formation; mixed bacterial-fungal biofilm infection; Staphylococcus aureus and Candida albicans most described microbials. Strategy - Local drug delivery scaffolds; development of poly-DL-lactic acid (PDLLA) scaffolds; co-delivery of antibacterial and antifungal drugs; minocycline and voriconazole as model drugs.
- Poly(DL-lactic acid) scaffolds adsorbed with minocycline and voriconazole: a new pathway towards infection containmentPublication . Zegre, Miguel; Henriques, M.; Santos, C.; Ribeiro, I. A.; Caetano, Liliana Aranha; Gonçalves, Lídia M.; Bettencourt, Ana F.Bone infection (osteomyelitis): burden as a clinical complication of orthopedic surgeries. Controlled antimicrobial release systems: treat and prevent osteomyelitis. Biomaterials based on porous scaffolds: local administration of high concentration of drugs; no systemic toxicity; extended time. Scaffolds in bone tissue engineering: a combination of bioresorbable polymers with bioactive bioglasses; present biodegradability and biosafety; suitable microenvironment and structure; favor osteogenic differentiation and cell growth. Co-encapsulation of drugs: advantageous means for administration of drugs; novel strategy directed to the co-delivery of two antimicrobials (voriconazole and minocycline).
- Templated synthesis of carbon materials mediated by porous clay heterostructuresPublication . Santos, C.; Andrade, M.; Vieira, A. L.; Martins, A.; Pires, J.; Freire, C.; Carvalho, A. P.Mesoporous carbon materials were prepared through template method approach using porous clay heterostructures (PCHs) as matrix and furfuryl alcohol as carbon precursor. Three PCHs prepared using amines with 8, 10 and 12 carbon atoms were used. The effect of several impregnation-polymerization cycles of the carbon precursor, the carbonization temperature and the need of a previous surface alumination were evaluated. The presence of two porosity domains was identified in all the carbon materials. These two domains comprise pores resulting from the carbonization of the polymer film formed in the inner structure of the PCH (domain I) and larger pores created by the clay particles aggregation (domain II). The predominance of the porosity associated to domain I or II can be achieved by choosing a specific amine to prepare the PCH matrix. Carbonization at 700 C led to the highest development of pores of domain I. In general, the second impregnation-polymerization cycle of furfuryl alcohol resulted in a small decrease of both types of porosity domains. Furthermore the previous acidification of the surface to create acidic sites proved to be unnecessary. The results showed the potential of PCHs as matrices to tailor the textural properties of carbons prepared by template mediated synthesis.