Sulforaphane-loaded hyaluronic acid-poloxamer hybrid hydrogel enhances cartilage protection in osteoarthritis models.

Sulforaphane (SFN) is an isothiocyanate with anti-arthritic and immuno-regulatory activities, supported by the downregulation of NF-κB pathway, reduction on metalloproteinases expression and prevention of cytokine-induced cartilage degeneration implicated in OA progression. SFN promising pharmacological effects associated to its possible use, by intra-articular route and directly in contact to the site of action, highlight SFN as promising candidate for the development of drug-delivery systems. The association of poloxamers (PL) and hyaluronic acid (HA) supports the development of osteotrophic and chondroprotective pharmaceutical formulations. This study aims to develop PL-HA hybrid hydrogels as delivery systems for SFN intra-articular release and evaluate their biocompatibility and efficacy for osteoarthritis treatment. All formulations showed viscoelastic behavior and cubic phase organization. SFN incorporation and drug loading showed a concentration-dependent behavior following HA addition. Drug release profiles were influenced by both diffusion and relaxation of polymeric chains mechanisms. The PL407-PL338-HA-SFN hydrogel did not evoke pronounced cytotoxic effects on either osteoblast or chondrosarcoma cell lines. In vitro/ex vivo pharmacological evaluation interfered with an elevated activation of NF-κB and COX-2, increased the type II collagen expression, and inhibited proteoglycan depletion. These results highlight the biocompatibility and the pharmacological efficacy of PL-HA hybrid hydrogels as delivery systems for SFN intra-articular release for OA treatment.

Electroactive nanofibers mats based on poly(l-lactic acid)/poly(ortho-ethoxyaniline) blends for biological applications.

The combination of scaffolds with desirable topographic characteristics and the use of electrical stimulus consist of a strategy to repair and regenerate tissues. An interesting approach to obtain electroactive scaffolds with the aforementioned features comprises on the use of conducting polymers which can be blended with other biocompatible polymers. In this work, poly(l-lactic acid) (PLLA) and poly(ortho-ethoxyaniline) (POEA) were synthesized and PLLA/POEA mats were prepared for the first time by electrospinning technique. Topographic characterization of PLLA/POEA showed a tunable mean diameter of the nanofibers by changing the electrospinning parameters. The presence of POEA into the blend was confirmed by X-ray photoelectron and Fourier-transform infrared spectroscopy analyses. Differential scanning calorimetry curves of PLLA/POEA exhibited shift positions of Tc and absence of the exothermic peak related to the characteristic isomerization process of POEA at high temperatures. The thermal analysis results indicate a favored miscibility between the polymers which is likely resulted from the strong interaction between polymers functionalities. The homogenous distribution of POEA chains throughout the scaffold rendered redox reversibility property for the mats. Biocompatibility results showed non-cytotoxic features for PLLA/POEA, attesting this novel system as a promising candidate for biological applications.

Cell interactions and cytotoxic studies of cellulose nanofibers from Curauá natural fibers.

Cellulose nanofibers (CNF) were isolated from Curauá fibers (Ananas erectifolius L. B. Smith) through a mechanical grinder preceded by mild chemical treatment. Morphology and surface characteristics of the fibers were followed until it reaches the nanoscale as long and flexible nanofibers. In aqueous suspensions, SAXS techniques revealed that such nanofibers present a twisted ribbon structure while rheological measurements demonstrate its high viscosity and a thixotropic behavior. These characteristics suggests the potential application of CNF in biomedical field, which, in turn, stimulates the toxicological studies of such materials. The obtained materials do not show any sign of cytotoxicity by direct or indirect assays for cell viability and cell morphology using Vero cells. Moreover, during the adhesion test, the cells demonstrated higher affinity to the CNF surface. It can be related to its surface properties and its obtaining conditions, which did not use any hazardous chemicals.

Evaluation of cell interaction with polymeric biomaterials based on hyaluronic acid and chitosan.

Tissue engineering involves the development of new materials or devices capable of specific interactions with biological tissues, searching the use of biocompatible materials as scaffolds for in vitro cell growth, and functional tissue development, that is subsequently implanted into patient. The aim of the current study was to evaluate the initial aspects of cell interaction with the polymeric biomaterials blends based on hyaluronic acid with chitosan. The hypothesis approach involves synthesis and analysis of swelling and thermal degradation (thermal gravimetric analysis) of the polymer blend; and Vero cell interaction with the biomaterial, through analysis of cytotoxicity, adhesion and cell morphology. The blend resulted in a biomaterial with a high swelling ratio that can allow nutrient distribution and absorption. The thermal gravimetric analysis results showed that the blend had two stages of degradation at temperatures very close to those observed for pure polymers, confirming that the physical mixing of hydrogels occurred, resulting in the presence of both hyaluronic acid and chitosan in the blend. The evaluation of indirect cytotoxicity showed that the blend was non cytotoxic for Vero cells, and the quantitative analysis performed with the MTT could verify a cell viability of 98%. The cells cultured on the blend showed adhesion, spreading and proliferation on this biomaterial, distinguished from the pattern of the control cells. These results showed that the blends produced from hyaluronic acid and chitosan hydrogels are promising for applications in tissue engineering, aiming at future cartilaginous tissue.

Cyclodextrin-Based Delivery Systems for Arthritic Diseases: From Development to Experimental Therapeutics.

Arthritics diseases, such as rheumatoid arthritis and osteoarthritis are chronic inflammatory and one of the most prevalent health conditions that cause disability (pain and functional limitation of joints). Despite the research advances, the treatment of those pathological conditions remains ineffective, since the pharmacological therapy is palliative, reducing only the symptoms and, in some cases, the chronic progression of the disease. In this context, the development of new formulations for controlled release would be interesting for reducing the number of injections and would also increase the patient compliance. In this article, we present a review of the cyclodextrin (CD)-based delivery systems focusing from conventional guest-host inclusion complexes and CD-polysulphates, until supramolecular architectures such as drug-CD-polymers conjugates, pseudorotaxanes, hydrogels as well as double-carrier systems and other systems. In particular, this article focuses the main CD-based delivery systems described in the literature emphasizing their possible administration by intra-articular route on the treatment of arthritic diseases, concentrating on their development and also performance as in vivo experimental therapeutic systems.

AUTOLOGOUS CHONDROCYTE TRANSPLANTATION-SERIES OF 3 CASES.

Hyaline cartilage covers joint surfaces and plays an important role in reducing friction and mechanical loading on synovial joints such as the knee. This tissue is not supplied with blood vessels, nerves or lymphatic circulation, which may be one of the reasons why joint cartilage has such poor capacity for healing. Chondral lesions that reach the subchondral bone (osteochondral lesions) do not heal and may progress to arthrosis with the passage of time. In young patients, treatment of chondral defects of the knee is still a challenge, especially in lesions larger than 4 cm. One option for treating these patients is autologous chondrocyte transplantation/implantation. Because this treatment does not violate the subchondral bone and repairs the defect with tissue similar to hyaline cartilage, it has the theoretical advantage of being more biological, and mechanically superior, compared with other techniques. In this paper, we describe our experience with autologous chondrocyte transplantation/implantation at the Institute of Orthopedics and Traumatology, Hospital das Clínicas, University of Sâo Paulo, through a report on three cases.

Transplante autólogo de condrócitos: relato de três casos / Autologous chondrocyte implantation: series of 3 cases

A cartilagem hialina recobre as superfícies articulares e tem um papel importante na redução da fricção e da carga mecânica das articulações sinoviais, como o joelho. Este tecido não é suprido de vasos, nervos ou circulação linfática, o que pode ser uma das razões pela qual a cartilagem articular tem uma péssima capacidade de cicatrização. As lesões condrais, quando atingem o osso subcondral (lesão osteocondral), não cicatrizam e podem progredir para artrose com o passar do tempo. Em pacientes jovens, o tratamento dos defeitos condrais do joelho ainda é um desafio, principalmente as lesões maiores de 4cm. Uma das opções de tratamento nesses pacientes é o transplante autólogo de condrócitos, que por não violar o osso subcondral e por reparar o defeito com tecido semelhante à cartilagem hialina, teria a vantagem teórica de ser mais biológico e mecanicamente superior, quando comparado a outras técnicas. Descreveremos nesse artigo a experiência do Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Universidade de São Paulo (IOT-HCFMUSP) com o transplante autólogo de condrócitos (ACI), através do relato de três casos.

Hyaline cartilage in the surface of synovial joints plays an important role in lowering stress and attrition in joints such as the knee. This tissue has no blood vessels, nerves, nor lymphatic drainage, which in part explains why articular cartilage has such poor capacity for healing. Chondral lesions reaching the subchondral bone (osteochondral lesions) do not heal and may progress to osteoarthritis as time passes. In young patients, treatment of such defects is challenging, especially in lesions larger than 4 cm. One option in young adults is the autologous chondrocyte implantation, capable of filling the defect with tissue similar to hyaline cartilage without violating the subchondral bone. Theoretically, it has biological and mechanical advantages over other surgical options. In this paper, we describe the experience with this procedure in a series of 3 cases at the Institute of Orthopedics and Traumatology, University of São Paulo.

Implante autólogo de condrócitos para o tratamento de lesão do côndilo femoral e talo / Autologous chondrocyte implantation to treat femoral condyle and talar lesions

Objetivo: Relatar os primeiros casos de implante autólogo de condrócitos no Brasil. Métodos: Foram selecionados pacientes jovens, com lesões traumáticas localizadas no côndilo femoral e talo. A avaliação clínica foi realizada com exames imaginológicos e artroscopias. Resultados: Foi observado o preenchimento da lesão com o tecido neoformado. Os pacientes apresentaram melhora de qualidade de vida, retomando as atividades cotidianas e esportivas. Conclusões: Concluiu-se que o implante autólogo de condrócitos é uma técnica promissora para o tratamento de lesões condrais do côndilo femoral e do talo.