Tendon Aging.

Tendons are mechanosensitive connective tissues responsible for the connection between muscles and bones by transmitting forces that allow the movement of the body, yet, with advancing age, tendons become more prone to degeneration followed by injuries. Tendon diseases are one of the main causes of incapacity worldwide, leading to changes in tendon composition, structure, and biomechanical properties, as well as a decline in regenerative potential. There is still a great lack of knowledge regarding tendon cellular and molecular biology, interplay between biochemistry and biomechanics, and the complex pathomechanisms involved in tendon diseases. Consequently, this reflects a huge need for basic and clinical research to better elucidate the nature of healthy tendon tissue and also tendon aging process and associated diseases. This chapter concisely describes the effects that the aging process has on tendons at the tissue, cellular, and molecular levels and briefly reviews potential biological predictors of tendon aging. Recent research findings that are herein reviewed and discussed might contribute to the development of precision tendon therapies targeting the elderly population.

Development and Characterization of Highly Stable Silver NanoParticles as Novel Potential Antimicrobial Agents for Wound Healing Hydrogels.

Recurrent microbial infections are a major cause of surgical failure and morbidity. Wound healing strategies based on hydrogels have been proposed to provide at once a barrier against pathogen microbial colonization, as well as a favorable environment for tissue repair. Nevertheless, most biocompatible hydrogel materials are more bacteriostatic than antimicrobial materials, and lack specific action against pathogens. Silver-loaded polymeric nanocomposites have efficient and selective activity against pathogenic organisms exploitable for wound healing. However, the loading of metallic nanostructures into hydrogels represents a major challenge due to the low stability of metal colloids in aqueous environments. In this context, the aim of the present study was the development of highly stable silver nanoparticles (AgNPs) as novel potential antimicrobial agents for hyaluronic acids hydrogels. Two candidate stabilizing agents obtained from natural and renewable sources, namely cellulose nanocrystals and ulvan polysaccharide, were exploited to ensure high stability of the silver colloid. Both stabilizing agents possess inherent bioactivity and biocompatibility, as well as the ability to stabilize metal nanostructures thanks to their supramolecular structures. Silver nitrate reduction through sodium borohydride in presence of the selected stabilizing agents was adopted as a model strategy to achieve AgNPs with narrow size distribution. Optimized AgNPs stabilized with the two investigated polysaccharides demonstrated high stability in phosphate buffer saline solution and strong antimicrobial activity. Loading of the developed AgNPs into photocrosslinked methacrylated hyaluronic acid hydrogels was also investigated for the first time as an effective strategy to develop novel antimicrobial wound dressing materials.

Bi-directional modulation of cellular interactions in an in vitro co-culture model of tendon-to-bone interface.

OBJECTIVES: This work aimed at studying in vitro interactions between human tendon-derived cells (hTDCs) and pre-osteoblasts (pre-OBs) that may trigger a cascade of events involved in enthesis regeneration. MATERIALS AND METHODS: The effect of 5 osteogenic medium (OM) conditions over the modulation of hTDCs and pre-OBs towards the tenogenic and osteogenic phenotypes, respectively, was studied. Three different medium conditions were chosen for subsequently establishing a direct co-culture system in order to study the expression of bone, tendon and interface-related markers. RESULTS: A higher matrix mineralization and ALP activity was observed in co-cultures in the presence of OM. Higher transcription levels of bone- (ALPL, RUNX2, SPP1) and interface-related genes (ACAN, COMP) were found in co-cultures. The expression of aggrecan was influenced by the presence of OM and cell-cell interactions occurring in co-culture. CONCLUSIONS: The present work assessed both the influence of OM on cell phenotype modulation and the importance of co-culture models while promoting cell-cell interactions and the exchange of soluble factors in triggering an interface-like phenotype to potentially modulate enthesis regeneration.

Seaweed polysaccharide-based hydrogels used for the regeneration of articular cartilage.

This manuscript provides an overview of the in vitro and in vivo studies reported in the literature focusing on seaweed polysaccharides based hydrogels that have been proposed for applications in regenerative medicine, particularly, in the field of cartilage tissue engineering. For a better understanding of the main requisites for these specific applications, the main aspects of the native cartilage structure, as well as recognized diseases that affect this tissue are briefly described. Current available treatments are also presented to emphasize the need for alternative techniques. The following part of this review is centered on the description of the general characteristics of algae polysaccharides, as well as relevant properties required for designing hydrogels for cartilage tissue engineering purposes. An in-depth overview of the most well known seaweed polysaccharide, namely agarose, alginate, carrageenan and ulvan biopolymeric gels, that have been proposed for engineering cartilage is also provided. Finally, this review describes and summarizes the translational aspect for the clinical application of alternative systems emphasizing the importance of cryopreservation and the commercial products currently available for cartilage treatment.

Periodontal tissue engineering strategies based on nonoral stem cells.

Periodontal disease is an inflammatory disease which constitutes an important health problem in humans due to its enormous prevalence and life threatening implications on systemic health. Routine standard periodontal treatments include gingival flaps, root planning, application of growth/differentiation factors or filler materials and guided tissue regeneration. However, these treatments have come short on achieving regeneration ad integrum of the periodontium, mainly due to the presence of tissues from different embryonic origins and their complex interactions along the regenerative process. Tissue engineering (TE) aims to regenerate damaged tissue by providing the repair site with a suitable scaffold seeded with sufficient undifferentiated cells and, thus, constitutes a valuable alternative to current therapies for the treatment of periodontal defects. Stem cells from oral and dental origin are known to have potential to regenerate these tissues. Nevertheless, harvesting cells from these sites implies a significant local tissue morbidity and low cell yield, as compared to other anatomical sources of adult multipotent stem cells. This manuscript reviews studies describing the use of non-oral stem cells in tissue engineering strategies, highlighting the importance and potential of these alternative stem cells sources in the development of advanced therapies for periodontal regeneration.