a b s t r a c t hLF1-11 (GRRRRSVQWCA) is an antimicrobial peptide (AMP) with high activity against methicillin-resistant Staphylococcus aureus (MRSA), the most prevalent species in implant-associated infection. In this work, the effect of the surface immobilization on hLF1-11 antimicrobial activity was studied. Immobilization was performed onto chitosan thin films as a model for an implant coating due to its reported osteogenic and antibacterial properties. Chitosan thin films were produced by spin-coating on gold surfaces. hLF1-11 was immobilized onto these films by its C-terminal cysteine in an orientation that exposes the antimicrobial activity-related arginine-rich portion of the peptide. Two levels of exposure (with and without a polyethylene glycol (PEG) spacer) were analyzed. Covalent immobilization was further compared with the AMP physical adsorption onto chitosan films. Surfaces were characterized using ellipsometry, contact angle measurements, atomic force microscopy, infrared and X-ray photoelectron spectroscopies and using a fluorimetric assay for hLF1-11 quantification. Surface antimicrobial activity was assessed through surface adhesion and viability assays using an MRSA (S. aureus ATCC 33591). The incorporation of hLF1-11 increased significantly bacterial adhesion to chitosan films. However, the presence of hLF1-11, namely when immobilized through a PEG spacer, decreased the viability of adherent bacteria with regard to the control surface. These results demonstrated that hLF1-11 after covalent immobilization by its cysteine can maintain activity, particularly if a spacer is applied. However, further studies, exploring the opposite orientation or the same C-terminal orientation, but non-cysteine related, can help to clarify the potential of the hLF1-11 immobilization strategy.

The outcome of cell-based therapies can benefit from carefully designed cell carriers. A multifunctional injectable vehicle for the co-delivery of human mesenchymal stem cells (hMSCs) and osteoinductive peptides is proposed, to specifically direct hMSCs osteogenic differentiation. The osteogenic growth peptide (OGP) inspired the design of two peptides, where the bioactive portion of OGP was flanked by a protease-sensitive linker, or its scrambled sequence, to provide faster and slower release rates, respectively. Peptides were fully characterized and chemically grafted to alginate. Both OGP analogs released bioactive fragments in vitro, at different kinetics, which stimulated hMSCs proliferation and osteogenesis. hMSCs-laden OGP-alginate hydrogels were tested at an ectopic site in a xenograft mouse model. After 4 weeks, OGP-alginate hydrogels were more degraded and colonized by vascularized connective tissue than the control (without OGP). hMSCs were able to proliferate, migrate outward the hydrogels, produce endogenous extracellular matrix and mineralize it. Moreover, OGP-groups stimulated hMSCs osteogenesis, as compared with the control. Overall, the ability of the proposed platform to direct the fate of transplanted hMSCs in loco was demonstrated, and OGP-releasing hydrogels emerged as a potentially useful system to promote bone regeneration.

A B S T R A C TCeramic/polymer-based biocomposites have emerged as potential biomaterials to fill, replace, repair or regenerate injured or diseased bone, due to their outstanding features in terms of biocompatibility, bioactivity, injectability, and biodegradability. However, these properties can be dependent on the amount of ceramic component present in the polymer-based composite. Therefore, in the present study, the influence of nanohydroxyapatite content (30 to 70 wt%) on alginate-based hydrogels was studied in order to evaluate the best formulation for maximizing bone tissue regeneration. The composite system was characterized in terms of physic-chemical properties and biological response, with in vitro cytocompatibility assessment with human osteoblastic cells and ex vivo functional evaluation in embryonic chick segmental bone defects. The main morphological characteristics of the alginate network were not affected by the addition of nanohydroxyapatite. However, physic-chemical features, like water-swelling rate, stability at extreme pH values, apatite formation, and Ca 2+ release were nanoHA dose-dependent. Within in vitro cytocompatibility assays it was observed that hydrogels with nanoHA 30% content enhanced osteoblastic cells proliferation and expression of osteogenic transcription factors, while those with higher concentrations (50 and 70%) decreased the osteogenic cell response. Ex vivo data underlined the in vitro findings, revealing an enhanced collagenous deposition, trabecular bone formation and matrix mineralization with Alg-nanoHA30 composition, while compositions with higher nanoHA content induced a diminished bone tissue response.The outcomes of this study indicate that nanohydroxyapatite concentration plays a major role in physicchemical properties and biological response of the composite system and the optimization of the components ratio must be met to maximize bone tissue regeneration.

These results suggest that 3.0 times the arterial diameter for the AVF size in dogs leads to greater venous flow than with 1.5 times the arterial diameter, without increasing the reversed flow.

In recent years, new highly functional polymeric biomaterials are being developed to increase the therapeutic efficacy in tissue regeneration approaches. Peptides regulate most physiological processes and display several other biological activities. Therefore, their importance in the field of biomedical research and drug development is rapidly increasing. However, the use of peptides as therapeutic agents is restricted by some of their physicochemical properties. The development of improved routes of delivery of peptide-based therapeutics is crucial and is crucial and its biomedical value is expected to increase in the near future. The unique properties of hydrogels triggered their spreading as localized drug depots. Several strategies, such as the carbodiimide chemistry, have been used to successfully immobilize bioactive peptide sequences into the hydrogels backbone. Peptide tethering through the so-called “click” chemistry reactions is also a highly promising, yet underexplored, approach to the synthesis of hydrogels with varying dimensions and patterns. The present review focus on the approaches that are being used for the establishment of chemical bonds between peptides and non-peptidic hydrogels throughout the last decade.

IntroduçãoCom a evolução dos estudos na área dos transplantes hepáticos, modelos experimentais de isquemia hepática têm sido muito difundidos. Além dos transplantes hepáticos, esses modelos podem ser utilizados em inúmeras outras situações, como em ressecções hepáticas, trauma com lesão hepática e choque hemodinâmico.Os pesquisadores dividem-se em duas grandes linhas: os que trabalham com modelos experimentais de isquemia hepáti-ca parcial 1,2,3,4,5,6 e os que trabalham com modelos de isquemia hepática total acrescida de derivação vascular 7,8,9,10 . Esses modelos são utilizados, exatamente, para se evitar a congestão esplâncnica, a isquemia intestinal e conseqüente endotoxemia.Com relação aos estudos experimentais de isquemia hepática total e suas repercussões no intestino, poucos são os trabalhos encontrados. Sébe 11 observou que, no modelo de isquemia hepática total sem derivação vascular, o clampeamento total do hilo hepático com pinça vascular (manobra de PRINGLE) por mais de vinte minutos leva a lesões nas organelas dos hepatócitos e congestão nos órgãos que são drenados pela veia porta, tais como o baço e intestino delgado. Sébe e col. (2000) 12 , estudando o intestino de ratos após o clampeamento total do hilo hepático, relatam que quanto maior o tempo de clampeamento maior a congestão esplâncnica e, aos 30 minutos, ocorre o desprendimento do revestimento das vilosidades intestinais e hemorragia.No presente trabalho procurou-se utilizar modelo de isquemia hepática total, sem derivação vascular, para poder-se estudar os eventos que ocorrem no intesti-

OBJETIVO: Identificar a terminologia adotada pelo editor para designar os membros do corpo editorial e atribuições pertinentes aos componentes da equipe responsável pela política, administração e qualidade do conteúdo da revista. Propor organograma do periódico e fluxograma do artigo. MÉTODOS: Foram analisados fascículos mais recentes de periódicos selecionados, disponíveis no Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde e em várias bibliotecas médicas do Brasil, apresentados na primeira parte desta linha de pesquisa. Nesta amostragem identificou-se a terminologia e as atribuições adotadas pelos editores de cada revista para designar os responsáveis pela forma e conteúdo do periódico. RESULTADOS: A terminologia adotada para o corpo editorial constante de cada revista foi levantada mostrando a diversificação de termos adotados para funções semelhantes. Foram identificados 74 termos, designando atividades exercidas pelos membros do corpo editorial, envolvidos com a produção e difusão da revista, e agrupados em 5 categorias. Visto sob a perspectiva de editoração, quer impressa ou eletrônica, a categorização das diferentes etapas do processo proporcionou os subsídios necessários para a elaboração do "Organograma da Revista Científica". A interpretação das atividades e responsabilidades de cada membro no organograma está descrita no "Perfil e responsabilidades de membro do corpo editorial". Ao inserir cada membro do corpo editorial, de acordo com as respectivas responsabilidades, foi possível elaborar o "Fluxograma do artigo". CONCLUSÃO: Não há uniformidade de termos e atribuições para a designação dos membros do corpo editorial nos periódicos estudados. Propõe-se organograma do periódico e fluxograma do artigo.

Foi realizado clampeamento do pedículo hepático de rato por diferentes tempos e estudadas as repercussões nos intestinos. Para tanto foram utilizados 40 ratos, machos, divididos em quatro grupos de 10 animais cada. O grupo S (Sham) não foi submetido a isquemia, já os grupos E1, E2 e E3 sofreram isquemia de 10, 20 e 30 minutos respectivamente. Nossos resultados mostraram alterações macroscópicas quanto a cor dos intestinos nos grupos E2 (20') e E3 (30') e histopatológicas que ocorreram em cada um desses grupos. Observou-se que quanto maior o tempo de clampeamento do pedículo hepático, maior a congestão esplâncnica, sendo que aos 30 minutos ocorreu o despreendimento do revestimento epitelial das vilosidades intestinais e hemorragia.