Smart implants as a novel strategy to regenerate well-founded cartilage

Here we explore a new generation of smart, living implants, combining not only active therapeutics but also stem cells, as a novel strategy to regenerate stabilised cartilage and avoid prostheses. This process can regenerate the subchondral bone foundation, which is currently difficult in the clinic

Nano-Engineered Scaffold for Osteoarticular Regenerative Medicine

In the last decade, regenerative medicine has benefited from the exponential development of nanomaterial sciences, tissue engineering and cell-based therapies. More and more sophisticated designed structures and surface topologies are being developed to basically mimic the extracellular matrix of native tissues such as cartilage and bone. Here we give an overview of the progress made in osteochondral lesion repair, with nano-engineered scaffolds comprising building blocks such as nanoparticles, nanotubes, layer-by-layer nano-assemblies, molecular self-assembly, nanopatterned surfaces…. This nano-engineering technology is coupled with bio-functionalization, by the use of adhesion peptides, growth factors, or deoxyribonucleic acid, to drive cell adhesion, proliferation and behavior towards tissue regeneration. In osteochondral regeneration, the challenge is the simultaneous development of chondrocytes and cartilage extracellular matrix on the one side and a well vascularized bone tissue with osteoblasts on the other sid

Advanced nanostructured medical device combining mesenchymal cells and VEGF nanoparticles for enhanced engineered tissue vascularization.

AIM: Success of functional vascularized tissue repair depends on vascular support system supply and still remains challenging. Our objective was to develop a nanoactive implant enhancing endothelial cell activity, particularly for bone tissue engineering in the regenerative medicine field. MATERIALS & METHODS: We developed a new strategy of tridimensional implant based on cell-dependent sustained release of VEGF nanoparticles. These nanoparticles were homogeneously distributed within nanoreservoirs onto the porous scaffold, with quicker reorganization of endothelial cells. Moreover, the activity of this active smart implant on cells was also modulated by addition of osteoblastic cells. RESULTS & CONCLUSION: This sophisticated active strategy should potentiate efficiency of current therapeutic implants for bone repair, avoiding the need for bone substitutes

Nanoscale Stiffness Distribution in Bone Metastasis

Nanomechanical heterogeneity is expected to have an effect on elasticity, injury and bone remodelling. In normal bone, we have two types of cells (osteoclasts and osteoblasts) working together to maintain existing bone. Bone cancers can produce factors that make the osteoclasts work harder. This means that more bone is destroyed than rebuilt, and leads to weakening of the affected bone. We report here the first demonstration of the nanoscale stiffness distribution in bone metastases before and after treatment of animals with the bisphosphonate Risedronate, a drug which is currently used for the treatment of bone metastases in patients with advanced cancers. The strategy used here is applicable to a wide class of biological tissues and may serve as a new reflection for biologically inspired scaffolds technologies

Implication of Toll/IL-1 receptor domain containing adapters in -induced inflammation

Periodontitis is induced by periodontal dysbiosis characterized by the predominance of anaerobic species. TLRs constitute the classical pathway for cell activation by infection. Interestingly, the Toll/IL-1 receptor homology domain adapters initiate signaling events, leading to the activation of the expression of the genes involved in the host immune response. The aim of this study was to evaluate the effects of Porphyromonas gingivalis on the expression and protein-protein interactions among five TIR adapters (MAL, MyD88, TRIF, TRAM and SARM) in gingival epithelial cells and endothelial cells. It was observed that P. gingivalis is able to modulate the signaling cascades activated through its recognition by TLR4/2 in gingival epithelial cells and endothelial cells. Indeed, MAL-MyD88 protein-protein interactions associated with TLR4 was the main pathway activated by P. gingivalis infection. When transient siRNA inhibition was performed, cell viability, inflammation, and cell death induced by infection decreased and such deleterious effects were almost absent when MAL or TRAM were targeted. This study emphasizes the role of such TIR adapter proteins in P. gingivalis elicited inflammation and the precise evaluation of TIR adapter protein interactions may pave the way for future therapeutics in both periodontitis and systemic disease with a P. gingivalis involvement, such as atherothrombosis

Updates on Anticancer Therapy-Mediated Vascular Toxicity and New Horizons in Therapeutic Strategies

International audienceVascular toxicity is a frequent adverse effect of current anticancer chemotherapies and often results from endothelial dysfunction. Vascular endothelial growth factor inhibitors (VEGFi), anthracyclines, plant alkaloids, alkylating agents, antimetabolites, and radiation therapy evoke vascular toxicity. These anticancer treatments not only affect tumor vascularization in a beneficial manner, they also damage ECs in the heart. Cardiac ECs have a vital role in cardiovascular functions including hemostasis, inflammatory and coagulation responses, vasculogenesis, and angiogenesis. EC damage can be resulted from capturing angiogenic factors, inhibiting EC proliferation, survival and signal transduction, or altering vascular tone. EC dysfunction accounts for the pathogenesis of myocardial infarction, atherothrombosis, microangiopathies, and hypertension. In this review, we provide a comprehensive overview of the effects of chemotherapeutic agents on vascular toxicity leading to hypertension, microvascular rarefaction thrombosis and atherosclerosis, and affecting drug delivery. We also describe the potential therapeutic approaches such as vascular endothelial growth factor (VEGF)-B and prokineticin receptor-1 agonists to maintain endothelial function during or following treatments with chemotherapeutic agents, without affecting anti-tumor effectiveness.Vascular toxicity is a frequent adverse effect of current anticancer chemotherapies and often results from endothelial dysfunction. Vascular endothelial growth factor inhibitors (VEGFi), anthracyclines, plant alkaloids, alkylating agents, antimetabolites, and radiation therapy evoke vascular toxicity. These anticancer treatments not only affect tumor vascularization in a beneficial manner, they also damage ECs in the heart. Cardiac ECs have a vital role in cardiovascular functions including hemostasis, inflammatory and coagulation responses, vasculogenesis, and angiogenesis. EC damage can be resulted from capturing angiogenic factors, inhibiting EC proliferation, survival and signal transduction, or altering vascular tone. EC dysfunction accounts for the pathogenesis of myocardial infarction, atherothrombosis, microangiopathies, and hypertension. In this review, we provide a comprehensive overview of the effects of chemotherapeutic agents on vascular toxicity leading to hypertension, microvascular rarefaction thrombosis and atherosclerosis, and affecting drug delivery. We also describe the potential therapeutic approaches such as vascular endothelial growth factor (VEGF) -B and prokineticin receptor-1 agonists to maintain endothelial function during or following treatments with chemotherapeutic agents, without affecting anti-tumor effectiveness

Réflexions éthiques autour de la recherche en ingénierie tissulaire osseuse [Ethical reflections on bone tissue engineering research]

Résumé L’ingénierie tissulaire osseuse représente aujourd’hui une stratégie de prise en charge des patients atteints de lésions osseuses pour laquelle les recherches foisonnent. Si elle représente indéniablement un grand espoir dans l’amélioration des pratiques cliniques et dans la diminution de l’incidence de complications, elle soulève aussi des réflexions éthiques qui se doivent d’accompagner son développement pour s’assurer d’être toujours dans l’intérêt du patient. Aussi, les réflexions menées dans cet article portent sur la nature et l’obtention des cellules utilisées pour l’ingénierie tissulaire osseuse, l’expérimentation animale, la responsabilité du chercheur face à la société, la sécurité à long terme et l’efficacité par rapport aux techniques actuelles, et enfin l’éthique et la déontologie du chercheur d’une manière plus globale. Ces thématiques rejoignent en grande partie celles de la recherche dans d’autres domaines. La littérature montre un intérêt, sinon une inquiétude, par rapport à ces questionnements éthiques, et invite les scientifiques et les éthiciens à s’engager davantage dans le débat

Does making method of alginate hydrogel influence the chondrogenic differentiation of human mesenchymal stem cells?

To overcome cartilage injury, strategies have been developed in the last few years based on tissue engineering to rebuild the defects. Cartilage engineering is principally based on three main biological factors: cells (native cells (chondrocytes) or a more primitive ones as mesenchymal stem cells), scaffolds and functionalization factors (growth factors, mechanical stimulation and/or hypoxia). Cartilage tissue engineering strategies generally result in homogeneous tissue structures with little resemblance to native zonal organization of articular cartilage. The main objective of our work concerns the buildup of complex biomaterials aimed at reconstructing biological tissue with three dimensional cells construction for mimicking cartilage architecture. Our strategy is based on structures formation by simple and progressive spraying of mixed alginate hydrogel and human mesenchymal stem cells (hMSC). In this work, the comportment of cells and more precisely their chondrogenic differentiation potential is compared to a traditional making process: the mold. We report here that spraying method allowed to product a scaffold with hMSC that confer a favorable environment for neocartilage construction.This work was supported by the "Lorraine region" grant. N. Jessel is indebted to CHU de Nancy, Hôpital Central, orthopedic surgery (Contrat d’interface INSERM-CHU).Not peer reviewe

Nano-Structured Ridged Micro-Filaments (≥100 µm Diameter) Produced Using a Single Step Strategy for Improved Bone Cell Adhesion and Proliferation in Textile Scaffolds

Textile scaffolds that are either 2D or 3D with tunable shapes and pore sizes can be made through textile processing (weaving, knitting, braiding, nonwovens) using microfilaments. However, these filaments lack nano-topographical features to improve bone cell adhesion and proliferation. Moreover, the diameter of such filaments should be higher than that used for classical textiles (10–30 µm) to enable adhesion and the efficient spreading of the osteoblast cell (>30 µm diameter). We report, for the first time, the fabrication of biodegradable nanostructured cylindrical PLLA (poly-L-Lactic acid) microfilaments of diameters 100 µm and 230 µm, using a single step melt-spinning process for straightforward integration of nano-scale ridge-like structures oriented in the fiber length direction. Appropriate drawing speed and temperature used during the filament spinning allowed for the creation of instabilities giving rise to nanofibrillar ridges, as observed by AFM (Atomic Force Microscopy). These micro-filaments were hydrophobic, and had reduced crystallinity and mechanical strength, but could still be processed into 2D/3D textile scaffolds of various shapes. Biological tests carried out on the woven scaffolds made from these nano-structured micro filaments showed excellent human bone cell MG 63 adhesion and proliferation, better than on smooth 30 µm- diameter fibers. Elongated filopodia of the osteoblast, intimately anchored to the nano-structured filaments, was observed. The filaments also induced in vitro osteogenic expression, as shown by the expression of osteocalcin and bone sialoprotein after 21 days of culture. This work deals with the fabrication of a new generation of nano-structured micro-filament for use as scaffolds of different shapes suited for bone cell engineering