Regenerative medicine is experiencing significant growth, driven by advances in stem cell biology, tissue engineering and implantable medical devices. Our topic designs combined innovative therapy medicinal products, integrating therapeutic matrices, stem cells and biofabrication technologies, to restore the function of bone and cartilage tissue damaged by trauma, disease or aging, with one constant objective: to accelerate the transfer of these innovations from the laboratory to the patient, through to clinical authorization and industrial development.
A combined innovative therapy medicinal product for the regeneration of isolated osteochondral lesions of the knee
Isolated osteochondral lesions of the knee affect more than 600 million people worldwide and, in the absence of appropriate treatment, represent one of the main risk factors for the progression to osteoarthritis. Current approaches (i.e. mosaicplasty, microfracture, prostheses) provide only partial and transient repair, resulting in the formation of fibrocartilage with insufficient mechanical quality. We have developed a next-generation combined innovative therapy medicinal product, associating a biodegradable nanofibrous membrane functionalized with BMP-2 nanoreservoirs for subchondral bone regeneration, with a hydrogel of autologous mesenchymal stem cells for the reconstruction of articular cartilage. The preclinical safety of this approach has been demonstrated in accordance with international regulatory standards (GLP), in small animals (murine model) and then in large animals (sheep), with non-invasive MRI monitoring and bone integration confirmed by micro-CT up to 26 weeks. This technology, protected by several patent families, led to the creation of the start-up Lamina Therapeutics, a spin-off of UMR1260 resulting from academic technology transfer. Lamina Therapeutics has obtained authorization from the EMA and the ANSM, via CTIS, to conduct a phase I clinical trial in Strasbourg, a world first for a combined innovative therapy medicinal product targeting the dual regeneration of subchondral bone and cartilage.
A custom-biofabricated innovative therapy medicinal product for meniscal repair
The meniscus, a heterogeneous and poorly vascularized fibrocartilaginous structure, cannot heal spontaneously after injury, which inevitably leads to knee osteoarthritis. Given the limitations of current techniques (arthroscopic repair limited to less than 10% of tears, allogeneic grafts with uncertain outcomes), our topic is developing, as part of a partnership with Japan (Cyfuse Biomedical, the European Centre for Japanese Studies in Alsace), a meniscal implant entirely biofabricated from the patient's own stem cells, without the use of a supporting biomaterial. Using Japanese scaffold-free 3D bioprinting technology (Cyfuse S-PIKE), spheroids differentiated into chondrocyte- and fibroblast-like cells are assembled according to the meniscus's native anisotropic architecture, then fused to form a custom functional tissue. This Franco-Japanese collaboration paves the way for personalized, vascularizable implants tailored to each patient's anatomy, with a prospective classification as an innovative therapy medicinal product.
A drug-screening device based on patient-derived vascularized microtissues
Our topic is developing an innovative device combining patient-derived vascularized bone microtissues with a perfusable microfluidic network, allowing faithful reproduction of the native bone microenvironment and its vascularization. This platform is then applied to the context of osteosarcoma, the most common primary bone tumor in children and adolescents, for which no major therapeutic progress has been made in three decades. By integrating patient-derived tumor microtissues within the same microfluidic network, our device makes it possible to directly compare the behavior of healthy bone tissue and tumor tissue, to perform rapid screening of therapeutic molecules, and to guide personalized clinical treatment, despite the tumor heterogeneity and microenvironmental complexity that currently limit the development of targeted therapies.
Scientific expertise
In the field of bone augmentation and regeneration, our topic masters the electrospinning of thin and thick implantable medical device structures, the design of hybrid bone substitutes and their nanofunctionalization, as well as the development of stem cell therapies, therapeutic scaffolds, and innovative therapy medicinal products, evaluated through in vitro, in vivo, preclinical, and clinical trials. Regarding cartilage regeneration, our topic covers the electrospinning of nanofibrous membranes, hydrogel formulation, nanofunctionalization, and 3D organoid-based stem cell therapies, likewise validated at every stage.
For meniscus regeneration and replacement, our topic relies on next-generation scaffold-free 3D biofabrication technology (Cyfuse S-PIKE), mesoscale tissue biofabrication, and well-organized 3D organoid stem cell therapies. In the field of personalized drug screening for osteosarcoma, our topic combines this same scaffold-free 3D biofabrication technology with vascularized hydrogel formulation and microfluidic chip devices.
Finally, our topic has developed recognized expertise in technology transfer and development, covering the entire continuum from academic proof of concept to clinical availability: patent filing and management, GMP-standard production, preparation of regulatory dossiers (IMPD-Q, IMPD-SE, Investigator's Brochure (IB), clinical protocol, etc.), and submission of clinical trial authorization applications to the EMA and the ANSM via CTIS. This integrated expertise led to the creation of the start-up Lamina Therapeutics, a spin-off of UMR1260, now authorized to conduct a phase I clinical trial.
Scientific topics
Regenerative Medicine
Advanced Therapy Medicinal Products (ATMP)
Implantable Medical Device
Highly innovative breakthrough medical devices
Nanomedicine
Material Science
Tissue Engineering
Stem cells
Keywords
Active living Biomaterials
Osteo-Articular Systems
Bone-tooth unit regeneration
Mesoscale Organoids
Organ-on-chip
Vascularized Matrix
Contributions to knowledge creation, sharing, and/or translation
Patented technology (3 licensed patents): EP2012052976, EP2020053761 et EP2020063549
Start-up Spin-off Lamina Therapeutics, Deeptech award, BPI France
Technology transfer (GMP production of the product Lamina.One, IMPD Quality)
Preclinical trial (IMPD Safety and Efficacy, Investigational Brochure)
Clinical trial (EMA-ANSM Authorization via CTIS application, Clinical protocol)
Topic main publications
Briand J.-P, Benkirane-Jessel N et al. A retro-inverso peptide corresponding to the GH loop of foot-and-mouth disease virus elicits high levels of long-lasting protective neutralizing antibodies. Proc Natl Acad Sci USA. 1997, 94:12545-12550. https://doi.org/10.1073/pnas.94.23.12545
Benkirane-Jessel N et al. Bioactive coatings based on a polyelectrolyte multilayer architecture functionalized by embedded proteins. Adv. Mater. 2004, 15:692-695. https://doi.org/10.1002/adma.200304634
Benkirane-Jessel N et al. Control of monocyte morphology on and response to model surfaces for implants equipped with anti-inflammatory agents. Adv. Materials, 2004, 16, 1507-1511. https://doi.org/10.1002/adma.200306613
Benkirane-Jessel N et al. Pyridylamino-beta-cyclodextrin as a molecular chaperone for lipopolysaccharide embedded in a multilayered polyelectrolyte architecture. Adv. Materials, 2004, 14, 963-969. https://doi.org/10.1002/adfm.200305089
Benkirane-Jessel N et al. Build-up of polypeptide multilayer coatings with anti-inflammatory properties based on the embedding of piroxicam-cyclodextrin complexes. Adv. Funct. Mater. 2004, 14:174-182. https://doi.org/10.1002/adfm.200304413
Benkirane-Jessel N et al. Short-time tuning of the biological activity of functionalized polyelectrolyte multilayers. Adv. Funct. Mater. 2005, 15:648-654. https://doi.org/10.1002/adfm.200400129
Benkirane-Jessel N et al. Multiple and time-scheduled in situ DNA delivery mediated by beta-cyclodextrin embedded in a polyelectrolyte multilayer. Proc Natl Acad Sci USA. 2006, 103:8618-8621. https://doi.org/10.1073/pnas.0508246103
Gangloff SC, Ladam G, Dupray V, Fukase K, Brandenburg K, Guenounou M, Schaaf P, Voegel J-C, Benkirane-Jessel N. Biologically active lipid A antagonist embedded in a multilayered polyelectrolyte architecture. Biomaterials. 2006, 27:1771-1777. https://doi.org/10.1016/j.biomaterials.2005.10.001
Dierich M, Le Guen E, Messadeq N, Netter P & Benkirane-Jessel N. Bone formation mediated by synergy-acting growth factors embedded in a polyelectrolyte multilayer film. Adv Mater 2007, 19: 693-697. https://doi.org/10.1002/adma.200601271
Nadiri A, Kuchler-Bopp S, Hu B, & Benkirane-Jessel N. Cells apoptosis Control by BMP-4 and Noggin embedded in a polyelectrolyte multilayer film. Small 2007, 3: 1577-1583. https://doi.org/10.1002/smll.200700115
Zhang X, Sharma KK, Boeglin M, Mainard D, Mély Y, Benkirane-Jessel N. Transfection ability and intracellular DNA pathway of nano-structured gene delivery systems. Nano Letters 2008, 8:2432-2436. https://doi.org/10.1021/nl801379y
Daubiné F, Cortial D, Ladam G, Atmani H, Clézardin P, Benkirane-Jessel N. Nanostructured polyelectrolyte multilayer drug delivery systems for bone metastasis prevention. Biomaterials 2009, 30: 6367-6373. https://doi.org/10.1016/j.biomaterials.2009.08.002
Grossin L, Cortial D, Saulnier B, Félix O, Decher G, Netter P, Gillet P, Mainard D, Benkirane-Jessel N. Step-by-step build-up of biologically active cell-containing stratified films aimed at tissue engineering. Adv Mater 2009, 21: 650-655. https://doi.org/10.1002/adma.200801541
Zhang X, Oulad-Abdelghani M, Zelkin AN, Wang Y, Mainard D, Caruso F, Benkirane-Jessel N. Poly(L-lysine) nanostructured particles for gene delivery and hormone stimulation. Biomaterials 2010, 31: 1699-1706. https://doi.org/10.1016/j.biomaterials.2009.11.032
Facca S, Cortez C, Mendoza-Palomares C, Messadeq N, Dierich A, Johnston APR, Mainard D, Voegel JC, Caruso F, Benkirane-Jessel N. Active multilayered capsules for in vivo bone formation. Proc Natl Acad Sci, 2010, 107, 3406-3411. https://doi.org/10.1073/pnas.0908531107
Fioretti F, Mendoza-Palomares C, Helms M, Al Alam D, Richert L, Arntz Y, Rinckenbach S, Garnier F, Haïkel Y, Gangloff S.C., Benkirane-Jessel N..Nanostructured assemblies for dental application. ACS Nano 2010, 4, 3277-87. https://doi.org/10.1021/nn100713m
Facca S, Lahiri D, Fioretti F, Agarwal A, Benkirane-Jessel N. In vivo osseointegration of nano-designed composite coatings on titanium implants. ACS Nano 2011, 5: 4790-4799. https://doi.org/10.1021/nn200768c
Mendoza-Palomares C, Ferrand A, Facca S, Fioretti F, Mainard D, Ladam G. Benkirane-Jessel N. Smart Hybrid Materials Equipped by Nanoreservoirs of Therapeutics. ACS Nano, 2012, 6, 483-490. https://doi.org/10.1021/nn203817t
Keller L, Wagner Q, Schwinté P, Benkirane-Jessel N. Double Compartmented and Hybrid Implant Outfitted with Well-Organized 3D Stem Cells for Osteochondral Regenerative Nanomedicine. Nanomedicine (Lond) 2015 10, 2833-2845. https://doi.org/10.2217/nnm.15.113
Keller L, Schwinté P, Gomez-Barrena E, Arruebo M and Benkirane-Jessel N. Smart Implants as Novel Strategy to Regenerate Well-Founded Cartilage. Trends in Biotechnology 2017, 35, 8–11. https://doi.org/10.1016/j.tibtech.2016.05.008
Keller L, Pijnenburg L, Idoux-Gillet Y, Bornert F, Benameur L, Tabrizian M, Auvray P, Rosset P, Gonzalo-Daganzo RM, Gomez Barrena E, Gentile L, Benkirane-Jessel N. Preclinical safety study of a combined therapeutic bone wound dressing for osteoarticular regeneration. Nat Commun 10, 2156 (2019). https://doi.org/10.1038/s41467-019-10165-5
Vignes H, Smaida R, Conzatti G, Hua G, Benkirane-Jessel N. Custom-made meniscus biofabrication. Trends Biotechnol2023 Dec;41(12):1467-1470. https://doi.org/10.1016/j.tibtech.2023.06.003
Meyer M, Smaida R, Fioretti F, Benkirane-Jessel N et al. Biomimetic Glycosaminoglycan-Enriched Electrospun Polymeric Scaffolds for Enhanced Early Tissue Regeneration. Journal of Functional Biomaterials 16, (2025). https://doi.org/10.3390/jfb16120447
Ali E.A.M., Smaida R, Benkirane-Jessel N et al. iPSCs chondrogenic differentiation for personalized regenerative medicine: a literature review. Stem Cell Res Ther 15, 185 (2024). https://doi.org/10.1186/s13287-024-03794-1
Lê H, Hua J, Benkirane-Jessel N et al. In vitro vascularized immunocompetent patient-derived model to test cancer therapies. iScience 26, (2023). https://doi.org/10.1016/j.isci.2023.108094
Lê H, Hua J, Benkirane-Jessel N et al. Patient-derived tumoroids and proteomic signatures: tools for early drug discovery. Front. Immunol. 15, (2024). https://doi.org/10.3389/fimmu.2024.1379613
Smaida R, Maugard L-P, Gegout H, Arruebo, M, Fioretti F, Benkirane-Jessel N, Favreau H. Osteoinductive and Biocompatibility Assessment of a 3D-Printed Polymeric–Hydroxyapatite Composite Interference Screw. Polymers 2026, 18, 1239. https://doi.org/10.3390/polym18101239
Smaida R, Hua G, Benkirane-Jessel N, Fioretti F. Three-Dimensional Models of the Dental Pulp: Bridging Fundamental Biology and Regenerative Therapy. Int J Mol Sci. 2025 Nov 12;26(22):10960. https://doi.org/10.3390/ijms262210960