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Contact

Dr. Matthias Schlund

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Contact

Linkedin biotis-bordeaux

Secretary Email

33 (0)5 57 57 14 88

Bioingénierie Tissulaire (BioTis)       

Physical Address:

Batiment BBS (Bordeaux Biologie Santé), 5e étage

2, rue du Dr Hoffmann Martinot,

33000, Bordeaux, France

Mailing Address:

Université de Bordeaux, Campus Carreire

146, rue Léo Saignat, Case 84,

33076, Bordeaux Cedex, France

Adhesive for bone fixation

Abstract

Reference

Project Leader

As a global public health issue [1], bone fractures are commonly treated by immobilization to restore the normal alignment and anatomy of the bone, which often involves surgical techniques using metallic hardware (plates, screws, and pins). Unfortunately, these metallic hardware items poorly adapt to certain specific situations, such as comminuted [2] or intra-articular fractures [3], and pediatric fractures in a growing skeleton [4]. Moreover, there may be mechanical or infectious complications associated with such devices, which require surgical removal for resolution [5]. However, hardware removal surgery may cause postoperative morbidity [6], which meanwhile generates a heavy economic burden [7].

▷[1] Wu AM, Bisignano C, James SL, Abady GG, Abedi A, Abu-Gharbieh E, et al. Global, regional, and national burden of bone fractures in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. The Lancet Healthy Longevity. 2021;2(9):e580‑92.

▷[2] Bergin PF, Weber TG, Gerow DE, Spitler CA, Graves ML, Russell GV. Intraosseous Plating for the Management of Cortical Defects. J Orthop Trauma. 2018;32 Suppl 1:S12‑7.

▷[3] Skroch L, Fischer I, Meisgeier A, Kozolka F, Apitzsch J, Neff A. Condylar remodeling after osteosynthesis of fractures of the condylar head or close to the temporomandibular joint. J Craniomaxillofac Surg. 2020;48(4):413‑20.

▷[4] Pontell ME, Niklinska EB, Braun SA, Jaeger N, Kelly KJ, Golinko MS. Resorbable Versus Titanium Hardware for Rigid Fixation of Pediatric Upper and Midfacial Fractures: Which Carries a Lower Risk Profile? J Oral Maxillofac Surg. 2021;79(10):2103‑14.

▷[5] Acklin YP, Bircher A, Morgenstern M, Richards RG, Sommer C. Benefits of hardware removal after plating. Injury. 2018;49 Suppl 1:S91‑5.

▷[6] Kellam PJ, Harrast J, Weinberg M, Martin DF, Davidson NP, Saltzman CL. Complications of Hardware Removal. J Bone Joint Surg Am. 2021;103(22):2089‑95.

▷[7] Lalli TAJ, Matthews LJ, Hanselman AE, Hubbard DF, Bramer MA, Santrock RD. Economic impact of syndesmosis hardware removal. Foot (Edinb). 2015;25(3):131‑3.

▷[8] Haugen HJ, Lyngstadaas SP, Rossi F, Perale G. Bone grafts: which is the ideal biomaterial? Journal of Clinical Periodontology. 2019;46(S21):92‑102.

▷[9] Samavedi S, Whittington AR, Goldstein AS. Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater. 2013;9(9):8037‑45.

▷[10] Habraken W, Habibovic P, Epple M, Bohner M. Calcium phosphates in biomedical applications: materials for the future? Materials Today. 1 mars 2016;19(2):69‑87.

▷[11] Zhang J, Liu W, Schnitzler V, Tancret F, Bouler JM. Calcium phosphate cements for bone substitution: chemistry, handling and mechanical properties. Acta Biomater. 2014;10(3):1035‑49.

▷[12] Shao H, Bachus KN, Stewart RJ. A water-borne adhesive modeled after the sandcastle glue of P. californica. Macromol Biosci. 2009;9(5):464‑71.

▷[13] Kirillova A, Kelly C, von Windheim N, Gall K. Bioinspired Mineral-Organic Bioresorbable Bone Adhesive. Adv Healthc Mater. 2018;7(17):e1800467.

▷[14] Pujari-Palmer M, Guo H, Wenner D, Autefage H, Spicer CD, Stevens MM, et al. A Novel Class of Injectable Bioceramics that Glue Tissues and Biomaterials. Materials (Basel). 2018;11(12).

▷[15] Norton MR, Kay GW, Brown MC, Cochran DL. Bone glue - The final frontier for fracture repair and implantable device stabilization. International Journal of Adhesion and Adhesives. 2020;102:102647.

▷[16] Waite JH. Mussel adhesion - essential footwork. J Exp Biol. 2017;220(Pt 4):517‑30.

▷[17] Lee H, Dellatore SM, Miller WM, Messersmith PB. Mussel-Inspired Surface Chemistry for Multifunctional Coatings. Science. 2007;318(5849):426‑30.

▷[18] Kaushik NK, Kaushik N, Pardeshi S, Sharma JG, Lee SH, Choi EH. Biomedical and Clinical Importance of Mussel-Inspired Polymers and Materials. Mar Drugs. 2015;13(11):6792‑817.

▷[19] Huang S, Liang N, Hu Y, Zhou X, Abidi N. Polydopamine-Assisted Surface Modification for Bone Biosubstitutes. Biomed Res Int. 2016;2016:2389895.

▷[20] Singh I, Dhawan G, Gupta S, Kumar P. Recent Advances in a Polydopamine-Mediated Antimicrobial Adhesion System. Front Microbiol. 2020;11:607099.

▷[21] Wu C, Han P, Liu X, Xu M, Tian T, Chang J, et al. Mussel-inspired bioceramics with self-assembled Ca-P/polydopamine composite nanolayer: Preparation, formation mechanism, improved cellular bioactivity and osteogenic differentiation of bone marrow stromal cells. Acta Biomaterialia. 2014;10(1):428‑38.

▷[22] Liu Z, Qu S, Zheng X, Xiong X, Fu R, Tang K, et al. Effect of polydopamine on the biomimetic mineralization of mussel-inspired calcium phosphate cement in vitro. Mater Sci Eng C Mater Biol Appl. 2014;44:44‑51.

▷[23] Liu Z, Chen J, Zhang G, Zhao J, Fu R, Tang K, et al. Enhanced Repairing of Critical-Sized Calvarial Bone Defects by Mussel-Inspired Calcium Phosphate Cement. ACS Biomater Sci Eng. 2018;4(5):1852‑61.

▷[24] Jin A, Wang Y, Lin K, Jiang L. Nanoparticles modified by polydopamine: Working as « drug » carriers. Bioact Mater. sept 2020;5(3):522‑41.

▷[25] Wang Z, Wang K, Zhang Y, Jiang Y, Lu X, Fang L, et al. Protein-Affinitive Polydopamine Nanoparticles as an Efficient Surface Modification Strategy for Versatile Porous Scaffolds Enhancing Tissue Regeneration. Particle & Particle Systems Characterization. 2016;33(2):89‑100.

▷[26] Xie X, Tang J, Xing Y, Wang Z, Ding T, Zhang J, et al. Intervention of Polydopamine Assembly and Adhesion on Nanoscale Interfaces: State-of-the-Art Designs and Biomedical Applications. Advanced Healthcare Materials. 2021;10(9):2002138.

▷[27] Ku SH, Ryu J, Hong SK, Lee H, Park CB. General functionalization route for cell adhesion on non-wetting surfaces. Biomaterials. 2010;31(9):2535‑41.


A bioresorbable and biodegradable bone glue would therefore be an excellent alternative. Furthermore, its use would not only be limited to traumatic bone fracture, but could also be extended to any surgery requiring bone healing or fusion such as osteotomies, bone graft fixation, and spinal fusion. It may also be used in conjunction with metallic implants, such as dental or arthroplastic implants, to enhance their primary stability. Despite such an evident need, there is currently no bone adhesive in clinical use that offers a strong enough bond and safe healing for wet bone.

Calcium phosphate cements (CPCs) are the most widely used bone substitute material in the field of bone regeneration [8] due to their chemical similarity to the inorganic phase of bone (hydroxyapatite) and their excellent biological properties [9,10]. Thanks to its great solubility under neutral pH conditions compared to other CPCs, tetracalcium phosphate (TTCP) is known for forming a paste with water, which progressively sets and hardens into a cement through a dissolution/precipitation process. Unfortunately, these cements have no intrinsic adhesive property to bone [11], thus limiting their use as bone adhesives.

Recently, inspired by marine creatures, notably the sandcastle worm (Phragmatopoma californica) [12], CPC-based bone adhesives were elaborated [13,15] by the addition of a phosphorylated amino acid, such as phosphoserine (OPS). Indeed, this key component of the sandcastle worm glue could self-reticulate with certain CPCs and form a biocompatible organo-mineral adhesive [13,15]. Therefore, the association of OPS and CPC seems to be a promising direction to develop high bond strength bone adhesives. These CPC/OPS bone adhesive materials are hybrid materials that have some similar limitations to CPCs, notably their mechanical properties and specifically their low adhesion, low strength, and brittleness, that often restrict their wider use and confine them to mostly non-loadbearing applications. Subsequently, considerable effort is needed to improve their mechanical properties.

A bio-inspired strategy may be applied to CPC/OPS bone adhesives to further improve their mechanical and/or biological properties. Indeed, polydopamine (PDA), which has a similar structural to key components of mussel foot adhesive proteins [16], has sparked considerable interest as a biomimetic and versatile coating for a wide range of materials including biomaterials [17,18]. In particular, thanks to its latent reactivity towards nucleophiles, PDA was used as a universal platform for surface biofunctionalization to promote the osteointegration of bone substitutes [19]. In the presence of amino acid-like lysine or OPS, PDA is able to anchor to various wet surfaces [20]. When combined with a CPC cement, PDA was shown to boost osteogenesis and osteointegration [21,23]. Nanoparticles of polydopamine (nPDA), which are formed by the self-polymerization of dopamine in basic conditions, exhibited remarkable drug loading capacity [24] in addition to all properties of PDA (25–27). Therefore, nPDA could be an ideal candidate for further improving the overall performance of CPC/OPS bone adhesive.

Thus, the present project aims to develop a bio-inspired bone adhesive based on a combination of TTCP, OPS, and nPDA.

In association with

-     Dr. Feng Chai, INSERM U1008, Univ. Lille

-     Pr. Joël Ferri, INSERM U1008, Univ. Lille

-     Pr. Joël Lyskawa, UMET, CNRS UMR 8207, Univ. Lille


Collaborator