RESUMEN
Methacrylated gellan gum (GGMA) formulation is proposed as a second-generation hydrogel for controlled delivery of cartilage-forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof-of-concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non-treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non-treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno-free biomaterial to be used with chondrogenic cells for a cost-effective treatment of focal chondral lesions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1987-1996, 2018.
Asunto(s)
Cartílago Articular/patología , Hidrogeles/farmacología , Metacrilatos/farmacología , Polisacáridos Bacterianos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Tejido Adiposo/citología , Animales , Cartílago Articular/efectos de los fármacos , Condrogénesis/efectos de los fármacos , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , ConejosRESUMEN
Osteoarthritis (OA) affects a large number of the population, and its incidence is showing a growing trend with the increasing life span. OA is the most prevalent joint condition worldwide, and currently, there is no functional cure for it. This review seeks to briefly overview the management of knee OA concerning standardized pharmaceutical and clinical approaches, as well as the new biotechnological horizons of OA treatment. The potential of biomaterials and state of the art of advanced therapeutic approaches, such as cell and gene therapy focused primarily on cartilage regeneration are the main subjects of this review. Biotechnol. Bioeng. 2017;114: 717-739. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Osteoartritis de la Rodilla/terapia , Materiales Biocompatibles , Cartílago Articular/citología , Cartílago Articular/fisiología , Terapia Genética , Humanos , Ingeniería de TejidosRESUMEN
Pro-inflammatory cytokines play a critical role in the development of autoimmune and inflammatory diseases. Targeting the cytokine environment has proven efficient for averting inflammation. In this study, we reported that 6-[4-(aminomethyl)-2-chlorophenoxyl]benzo[c][1,2]oxaborol-1(3H)-ol (AN3485), a benzoxaborole analog, inhibited TLR2-, TLR3-, TLR4-, and TLR5-mediated TNF-α, IL-1ß, and IL-6 release from human PBMCs and isolated monocytes with IC(50) values ranging from 18 to 580 nM, and the inhibition was mediated at the transcriptional level. Topical administration of AN3485 significantly reduced PMA-induced contact dermatitis and oxazolone-induced delayed-type hypersensitivity in mice, indicating its capability of penetrating skin and potential topical application in skin inflammation. Oral administration of AN3485 showed dose-dependent suppression of LPS-induced TNF-α and IL-6 production in mice with an ED(90) of 30 mg/kg. Oral AN3485, 35 mg/kg, twice a day, suppressed collagen-induced arthritis in mice over a 20-day period. The potent anti-inflammatory activity in in vitro and in vivo disease models makes AN3485 an attractive therapeutic lead for a variety of cutaneous and systemic inflammatory diseases.