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Xavier Garric

Xavier Garric

Professor, Faculty of pharmacy, University of Montpellier

Xavier Garric was born in Nice (France) in 1977. He first received his PharmD degree in 2001 before he obtained his PhD in 2004 from the University of Montpellier I, under the supervision of Doctors Michel Vert and Jean-Pierre Molès in the field of degradable polymeric scaffold in skin engineering. He joined the group of Doctor Michel Vert as an Assistant Professor at the University of Montpellier, in 2005. He was appointed Professor of Polymer Chemistry at the Faculty of Pharmacy in 2013 and became team leader in September 2018. His research interests are focused on biomedical applications of polymers and especially for the design of new drug delivery systems and degradable medical devices.
Part of his recent research is related to the design of an anti-adhesion, self-expanding and degradable medical device for the prevention of intra-uterine adhesions. This work led to the creation of the Womed start-up in 2018 of which he is co-founder and scientific advisor.
Another part of his research focuses on degradable elastomers for tissue engineering applications as the well as the development of new drug eluting system for implantable medical device.
Xavier is co-author of over 46 papers and 5 patents.
He is co-head of the master’s degree in health engineering, he is deputy director of the scientific chemistry department at the University of Montpellier.

Contact:

xavier.garric(a)umontpellier.fr
+33411759693

5 recent publications:

Pinese C, Gagnieu C, Nottelet B, Rondot-Couzin C, Hunger S, Coudane J, Garric X. In vivo evaluation of hybrid patches composed of PLA based copolymers and collagen/chondroitin sulfate for ligament tissue regeneration. J Biomed Mater Res B 2017;105:1778-88.

Guillaume O, Garric X, Lavigne JP, Van Den Berghe H, Coudane J. Multilayer, degradable coating as a carrier for the sustained release of antibiotics: Preparation and antimicrobial efficacy in vitro. J Control Release 2012;162:492-501.   IF 2016 = 7.786

Blanquer S, Guillaume O, Letouzey V, Lemaire L, Franconi F, Paniagua C, Coudane J, Garric X. New magnetic-resonance-imaging-visible poly(epsilon-caprolactone)-based polyester for biomedical applications. Acta Biomater 2012;8:1339-47.  IF 2016 = 6.319

Morille M, Tran Van T, Garric X, Coudane J, Venier-Julienne MC, Montero-Menei C. Microsphere compositions, preparation and method and applications thereof. WO2013144341

Coudane J, Leprince S, Garric X, Paniagua C, Huberlant S, Letouzey V. Composition of diblock and triblock copolymers and the use thereof in the prevention of tissues adhesions. WO2016020613

Double-hydrophilic block copolymers based on functional poly(ε-caprolactone)s for pH-dependent controlled drug delivery

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Biomacromolecules X, XXX, (2019)

Ayman El Jundi, Sytze Buwalda, Audrey Bethry, Sylvie Hunger, Jean Coudane, Youssef Bakkour, Benjamin Nottelet

 

ABSTRACT

The use of double-hydrophilic block copolymers (DHBCs) in biomedical applications is limited by their lack of degradability. This additional functionality has been obtained in the past through multistep chemical strategies associated with low yields. In this work, a series of DHBCs composed of a bioeliminable poly(ethylene glycol) (PEG) block and hydrolysable functional poly(e-caprolactone) (PCL) blocks bearing carboxylic (PEG-b-PCL(COOH)), amino (PEG-b-PCL(NH2)) or hydroxyl side groups (PEG-b-PCL(OH)) is synthesized in only 3 steps. DHBCs with 50% substitution degree with respect to the CL units are obtained for all functional groups. The pH-dependent self-assembly behavior of the DHBCs is studied showing critical micelle concentration (CMC) variations by a factor 2 upon pH changes and micellar mean diameter variations of 20-30%. The potential of these partly degradable DHBCs as drug-loaded polyion complex micelles is further exemplified with the PEG-b-PCL(COOH) series that is associated with the positively charged anticancer drug doxorubicin (DOX). Encapsulation efficiencies, drug loadings, pH-controlled release and cytotoxicity of the DOX-loaded micelles towards cancer cells are demonstrated. This set of data confirms the interest of the proposed straightforward chemical strategy to generate fully bioeliminable and partly degradable DHBCs with potential as pH-responsive drug delivery systems.

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Preliminary design of a new degradable medical device to prevent the formation and recurrence of intrauterine adhesions

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Communications Biology 2, 196, (2019)

Leprince, S., Huberlant, S., Allegre, L., Warembourg, S., Leteuff, I., Bethry, A., Paniagua, C., Taillades, H., Tayrac, R. D., Coudane, J., Letouzey, V. & Garric, X.

 

ABSTRACT

Intrauterine adhesions lead to partial or complete obliteration of the uterine cavity and have life-changing consequences for women. The leading cause of adhesions is believed to be loss of stroma resulting from trauma to the endometrium after surgery. Adhesions are formed when lost stroma is replaced by fibrous tissue that join the uterine walls. Few effective intrauterine anti-adhesion barriers for gynecological surgery exist. We designed a degradable anti-adhesion medical device prototype to prevent adhesion formation and recurrence and restore uterine morphology. We focused on ideal degradation time for complete uterine re-epithelialization for optimal anti-adhesion effect and clinical usability. We developed a triblock copolymer prototype [poly(lactide) combined with high molecular mass poly(ethylene oxide)]. Comparative pre-clinical studies demonstrated in vivo anti-adhesion efficacy. Ease of introduction and optimal deployment in a human uterus confirmed clinical usability. This article provides preliminary data to develop an intrauterine medical device and conduct a clinical trial.

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Degradable multi(aryl-azide) star copolymer as universal photo-crosslinker for elastomeric scaffolds

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Mater. Today Chem. 12, 209-221, (2019)

Gangolphe L., Déjean S., Bethry A., Hunger S., Pinese C., Garric X., Bossard F., Nottelet B.

ABSTRACT

Degradable elastomers with elastic properties close to those of soft-tissues are necessary for tissue-engineering. Most degradable elastomers developed so far are based on functional low molecular weight pre-polymers that are combined with molecular crosslinkers to yield the elastomeric 3D networks. To overcome this limitation, we present in this work the concept of star-shaped macromolecular multi(aryl-azide) photo-crosslinker that has the ability to efficiently crosslink any polymer containing C-H bonds independently of its molecular weight and without the need for pre-functionalization. This concept of universal crosslinking agent is illustrated with a star-shaped block copolymer composed of an 8-arm poly(ethylene glycol) core and poly(lactide) side arms functionalized with aryl-azide moieties (PEG8arm-PLA-fN3). It was selected due to its macromolecular nature that allows for an easy processing of electrospun photo-crosslinked scaffolds while making it possible to adapt its chemical nature with the one of the polymer matrix. A parameter study is first carried out on PEG8arm-PLA-fN3 / PLA-Pluronic®-PLA films to evaluate the impact of the polymers molecular weight, PEG/PLA ratios, and UV irradiation conditions on the crosslinking efficiency. This study confirms that high crosslinking efficiencies can be obtained with PEG8arm-PLA-fN3 (60%) compared to commercially availabe bis(aryl-azide) photo-crosslinker (below 15%). Optimal conditions are then used to yield electrospun microfibers (1-2 µm) crosslinked with PEG8arm-PLA-fN3 resulting in biocompatible and highly elastomeric scaffolds (ε_y>100%) compared to uncrosslinked scaffolds(ε_y<10%). In addition, we show that the degradation rate can be controlled over time depending on the blend content of PEG8arm-PLA-fN3. Taken together, these results demonstrate the potential of macromolecular multi(aryl-azide) photo-crosslinkers to develop original degradable elastomeric scaffolds for soft-tissue reconstruction.

UV-triggered photoinsertion of contrast agent onto polymer surfaces for in vivo MRI-visible medical devices

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Multifunct. Mater. 2 0240012019 (2019)

Schulz A., Lemaire L., Bethry A.; Allegre L., Cardoso M., Bernex F., Franconi F., Goze-Bac C., Taillades H., Garric X., Nottelet B.

ABSTRACT

Polymeric materials are largely employed for the manufacturing of implants for various reasons, but they are typically invisible by conventional imaging methods. To improve surgical procedure and postoperative implant follow-up though, biomaterials are needed which allow an accurate and efficient imaging. Here, we present a direct and versatile strategy that allows to covalently immobilize T1 magnetic resonance imaging (MRI) contrast agents at the surface of various clinically relevant polymeric biomaterials. An aryl-azide bearing complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and gadolinium (Gd) has been synthesized for easy photografting onto polymer surfaces. Polycaprolactone (PCL), polylactide (PLA), polyurethane (PU), polyetheretherketone (PEEK) and polypropylene (PP) have been selected as clinically relevant substrates and successfully functionalized with the photosensitive MRI probe DOTA/Gd. Following in vitro assessment of their biocompatibility and MRI visibility, commercial MRI-visible PP hernia repair meshes (MRI-meshes) have been prepared. MRI-meshes have been implanted in rats for in vivo evaluation of their imaging capacities over 1 month. Histological evaluation and Gd biodistribution studies have been carried out confirming the potential of this straightforward approach to simply yield imageable medical devices.