Innovative Drug Delivery Systems for Regenerative Medicine

In the past two decades, research on drug delivery systems has achieved significant advances [...

La transplantation rénale à partir de donneurs vivants

L'insuffisance rénale chronique terminale (IRCT) représente un enjeu majeur de santé publique en terme de coûts et d'invalidité. La prise en charge de cette maladie chronique repose en premier lieu sur la dialyse. Néanmoins, cette solution thérapeutique s'accompagne de contraintes handicapant le quotidien du patient et généralement celui de son entourage. La transplantation rénale offre une réelle avancée en terme de confort de vie inégalable associé à une meilleure survie du patient. Cependant, face à une pénurie d'organes alarmante, il est très difficile d'obtenir rapidement un greffon et le patient est inscrit en liste d'attente. C'est pourquoi, les équipes de transplantation sensibilisent le plus tôt possible le patient et sa famille sur la greffe rénale à partir de donneur vivant, solution idéale pour le patient. En effet, les chances de réussite sont largement en faveur de cette alternative. Le travail réalisé durant cette thèse tentera de démontrer en quoi la transplantation rénale à partir de donneurs vivants offre de meilleurs résultats, avec un risque pour le donneur considéré comme négligeable. Bien entendu, ce domaine particulier est strictement encadré par la loi afin de s'assurer du consentement libre et informé du donneur et d'éviter ainsi tout abus commercial. La transplantation rénale à partir de donneurs vivants soulève un certain nombre de problèmes : éthique, sanitaire, juridique... abordés au cours de cette thèse.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

The multiple therapeutic applications of miRNAs for bone regenerative medicine

International audienceWith the aging of the general population, there is an increasing need for bone defect repair, prompting the development of reliable alternatives to autologous bone grafting, without the usually associated major drawbacks (i.e., limited volume and severe postoperative pain). Given the crucial role that miRNAs appear to have in bone tissue physiopathology, exploring their potential has recently garnered increased interest. In this review, we first describe the involvement of miRNAs in bone metabolism, and then focus on their potential therapeutic applications (as bone biomarkers and molecular targets). We also highlight the as yet unsolved biological (i.e., off-target effects) and technological (i.e., specific delivering) challenges associated with their use

Fibrin as a Multipurpose Physiological Platform for Bone Tissue Engineering and Targeted Delivery of Bioactive Compounds

International audienceAlthough bone graft is still considered as the gold standard method, bone tissue engineering offers promising alternatives designed to mimic the extracellular matrix (ECM) and to guide bone regeneration process. In this attempt, due to their similarity to the ECM and their low toxicity/immunogenicity properties, growing attention is paid to natural polymers. In particular, considering the early critical role of fracture hematoma for bone healing, fibrin, which constitutes blood clot, is a candidate of choice. Indeed, in addition to its physiological roles in bone healing cascade, fibrin biochemical characteristics make it suitable to be used as a multipurpose platform for bioactive agents' delivery. Thus, taking advantage of these key assets, researchers and clinicians have the opportunity to develop composite systems that might further improve bone tissue reconstruction, and more generally prevent/treat skeletal disorders

Calcium phosphate biomaterials as bone drug delivery systems: a review

A short review is proposed on the existing literature for the research performed in calcium phosphate (CaP) biomaterials used as drug delivery systems. In the first part, a brief update is given on the performance of both CaP ceramics and CaP cements. Second, a review of the research and clinical situation is developed for CaP materials already used as drug delivery systems. Experimental works performed for local delivery are reported. In particular, a description is given of the in vitro and in vivo studies in which these materials are loaded with various proteins and drugs

Biphasic calcium phosphate ceramics for bone reconstruction: A review of biological response

International audienceAutologous bone graft is considered as the gold standard in bone reconstructive surgery. However, the quantity of bone available is limited and the harvesting procedure requires a second surgical site resulting in severe complications. Due to these limits, scientists and clinicians have considered alternatives to autologous bone graft. Calcium phosphates (CaPs) biomaterials including biphasic calcium phosphate (BCP) ceramics have proven efficacy in numerous clinical indications. Their specific physico-chemical properties (HA/TCP ratio, dual porosity and subsequent interconnected architecture) control (regulate/condition) the progressive resorption and the bone substitution process. By describing the most significant biological responses reported in the last 30 years, we review the main events that made their clinical success. We also discuss about their exciting future applications as osteoconductive scaffold for delivering various bioactive molecules or bone cells in bone tissue engineering and regenerative medicine. Statement of Significance Nowadays, BCPs are definitely considered as the gold standard of bone substitutes in bone reconstructive surgery. Among the numerous clinical studies in literature demonstrating the performance of BCP, Passuti et al. and Randsford et al. studies largely contributed to the emergence of the BCPs. It could be interesting to come back to the main events that made their success and could explain their large adhesion from scientists to clinicians. This paper aims to review the most significant biological responses reported in the last 30 years, of these BCP-based materials. We also discuss about their exciting future applications as osteoconductive scaffold for delivering various bioactive molecules or bone cells in bone tissue engineering and regenerative medicine

Photoinduced Storage and Thermal Release of Singlet Oxygen from 1,2-Dihydropyridine Endoperoxides

International audienceThe quest for molecules able to trap, store and release singlet oxygen is of utmost interest due to their applicability in various domains such as materials science and photomedicine. The aim of this study was to prepare and to study a new family of singlet oxygen donors based on the 1,2-dihydropyridine motif. The experiments demonstrated the influence of substituents and solvents on the photooxygenation rate constants. The process can be operated reversibly by thermolysis of the in-situ formed endoperoxide leading to a release of singlet oxygen and formation of the parent 1,2 dihydropyridine compound. A bifunctional structure based on a phenalenone photosensitizer covalently connected to a 1,2 dihydropyridine module was synthesized via a multi-step sequence. Upon irradiation with blue light, singlet oxygen was produced leading to the formation of the endoperoxide intermediate. In the dark cycle, the endoperoxide underwent cycloreversion reaction affording the parent 1,2-dihydropyridine unit paving the way to a continuous production of singlet oxygen during the light/dark cycles

Enhanced Corrosion Resistance and Local Therapy from Nano-Engineered Titanium Dental Implants

Titanium is the ideal material for fabricating dental implants with favorable biocompatibility and biomechanics. However, the chemical corrosions arising from interaction with the surrounding tissues and fluids in oral cavity can challenge the integrity of Ti implants and leach Ti ions/nanoparticles, thereby causing cytotoxicity. Various nanoscale surface modifications have been performed to augment the chemical and electrochemical stability of Ti-based dental implants, and this review discusses and details these advances. For instance, depositing nanowires/nanoparticles via alkali-heat treatment and plasma spraying results in the fabrication of a nanostructured layer to reduce chemical corrosion. Further, refining the grain size to nanoscale could enhance Ti implants’ mechanical and chemical stability by alleviating the internal strain and establishing a uniform TiO2 layer. More recently, electrochemical anodization (EA) has emerged as a promising method to fabricate controlled TiO2 nanostructures on Ti dental implants. These anodized implants enhance Ti implants’ corrosion resistance and bioactivity. A particular focus of this review is to highlight critical advances in anodized Ti implants with nanotubes/nanopores for local drug delivery of potent therapeutics to augment osseo- and soft-tissue integration. This review aims to improve the understanding of novel nano-engineered Ti dental implant modifications, focusing on anodized nanostructures to fabricate the next generation of therapeutic and corrosion-resistant dental implants. The review explores the latest developments, clinical translation challenges, and future directions to assist in developing the next generation of dental implants that will survive long-term in the complex corrosive oral microenvironment

Photodynamic Therapy for Peri-Implant Diseases

Peri-implant diseases are frequently presented in patients with dental implants. This category of inflammatory infections includes peri-implant mucositis and peri-implantitis that are primarily caused by the oral bacteria that colonize the implant and the supporting soft and hard tissues. Other factors also contribute to the pathogenesis of peri-implant diseases. Based on established microbial etiology, mechanical debridement has been the standard management approach for peri-implant diseases. To enhance the improvement of therapeutic outcomes, adjunctive treatment in the form of antibiotics, probiotics, lasers, etc. have been reported in the literature. Recently, the use of photodynamic therapy (PDT)/antimicrobial photodynamic therapy (aPDT) centered on the premise that a photoactive substance offers benefits in the resolution of peri-implant diseases has gained attention. Herein, the reported role of PDT in peri-implant diseases, as well as existing observations and opinions regarding PDT, are discussed