DS0404 - Innovation biomédicale

In vivo validation of new non-degradable hydrogel based ligament substitutes. – LIGAGEL2_CLOSER_TO_BEDSIDE

Submission summary

The anterior cruciate ligament (ACL) is a critical component for the maintenance of proper knee stability and kinematics. Rupture of this ligament is one of the most frequently occurring ligament injuries affecting about 1 person over 3000 every year. This trend has been constantly increasing with the rise of participation in sports in the general population and becomes a serious public health issue. Indeed, the loss in knee stability caused by ACL rupture prevents any return to normal sport practice and often leads to osteoarthritis of the knee joint on the long term. The current standard care is based on ligament reconstruction by autograft from tendon tissues and is considered as the gold standard. Yet, autograft reconstruction presents serious limitations including the limited availability of the graft, a long and painful recovery period associated with the donor site morbidity and a high probability of rupture at the initial stages. There is today a major and growing demand from surgeons and patients for an off-the-shelf alternate solution. The LIGAGEL2_CLOSER_TO_BEDSIDE project integrates in vivo evaluation into materials design to create the first clinically applicable prototypes of a novel ACL substitute made of biocompatible and non-degradable hydrogel fibers.

Current research efforts focus on tissue-engineering approaches using degradable substitutes and face major challenges to ensure the proper reconstruction of ligament tissues. This project will explore an original alternate approach by designing a permanent non-cellularized ACL substitute that could rapidly bring a new and improved solution to the clinic. These substitutes are obtained from the assembly of non-degradable hydrogel fibers offering greater biocompatibility and resistance to wear than dry polymeric structures. Our team will investigate how to exploit the unique swelling and self-lubricating properties of hydrogels to enhance bone anchoring and fatigue resistance. Performances will be characterized ex vivo on human cadaver knees and in vivo on the most relevant and recognized animal models. These results will be objectively quantified through comparisons with the best existing treatments.

This multidisciplinary project is based on the close collaboration of three complementary teams in the fields of materials science, biomechanics, ligament biology and surgery. Materials scientists at the Centre des Matériaux of Mines-ParisTech will design, fabricate and characterize in vitro prototypes of hydrogel ligaments. Orthopedic surgeons at the Bioingénierie et Bioimagerie OstéoArticulaire laboratory of Paris Diderot University will implant these substitutes and will assess their clinical relevance. They will be assisted by histologists to determine the biocompatility of the implant and the integration processes that are involved. Biomechanicians at the Laboratoire de Biomécanique of Arts-et-Métiers ParisTech will then quantify appropriately the restoration of the ligament mechanical function.

Prototypes of ACL substitute will be delivered that exhibit a novel combination of off-the-shelf availability, long-term biocompatibility and biomechanical functionality. This research will provide the demonstrations of safety and effectiveness required prior to the first clinical trials. The original approaches explored for the design of implantable hydrogels and for attachment between the ligament and bone will bring further progress. Discoveries and breakthroughs are anticipated in biological integration of polymers and repair of soft biological tissues.

Project coordination

Laurent Corté (ARMINES Centre des Matériaux de Mines ParisTech)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


ARTS LBM ARTS Laboratoire de Biomécanique des Arts et Métiers ParisTech
P7 B2OA UNIVERSITE PARIS DIDEROT Laboratoire de Bioingénierie et Bioimagerie OstéoArticulaire
ARMINES CdM ARMINES Centre des Matériaux de Mines ParisTech

Help of the ANR 450,695 euros
Beginning and duration of the scientific project: October 2014 - 48 Months

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