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Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition

Charles-Hubert Lafantaisie-Favreau, Jessica Guzmán-Morales, Jun Sun, Gaoping Chen, Adam Harris, Thomas D. Smith, Alberto Carli, Janet Henderson, William D. Stanish and Caroline D. Hoemann

Article (2013)

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Cite this document: Lafantaisie-Favreau, C.-H., Guzmán-Morales, J., Sun, J., Chen, G., Harris, A., Smith, T. D., ... Hoemann, C. D. (2013). Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition. BMC Musculoskeletal Disorders, 14. doi:10.1186/1471-2474-14-27
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Abstract

Background: In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls. Methods: Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair. Results: All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue. Conclusions: Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair.

Uncontrolled Keywords

Animals; Biocompatible Materials; Blood Coagulation; Bone Resorption; Cartilage Diseases; Cartilage, Articular; Chemotaxis; Chitosan; Drug Implants; Extracellular Matrix; Female; Knee Joint; Male; Models, Animal; Molecular Weight; Neutrophils; Rabbits; Regeneration; Stromal Cells; Thromboplastin; Time Factors; Wound Healing; X-Ray Microtomography; Biocompatible Materials; Drug Implants; Chitosan; Thromboplastin; Cartilage repair; Bone marrow; Osteoclast; Collagen; Marrow simulation; Bone remodeling; Mesenchymal stromal cell; Micro-computed tomography

Open Access document in PolyPublie
Subjects: 1800 Génie chimique > 1800 Génie chimique
1900 Génie biomédical > 1902 Matériaux biomédicaux
2000 Science et technologie des matériaux > 2006 Biomatériaux
9000 Sciences médicales > 9000 Sciences médicales
Department: Département de génie chimique
Research Center: Non applicable
Funders: CRSNG / NSERC, Canadian Institutes of Health Research (CIHR), Fonds de recherche Québec (FRSQ, CDH, FQRNT, JGM), Canadian Arthritis Network (AH, TDS), BiosSyntech Inc.
Grant number: STPGP 365025, 185810-BME
Date Deposited: 05 Dec 2018 16:43
Last Modified: 06 Dec 2018 01:20
PolyPublie URL: https://publications.polymtl.ca/3427/
Document issued by the official publisher
Journal Title: BMC Musculoskeletal Disorders (vol. 14)
Publisher: BioMed Central Ltd
Official URL: https://doi.org/10.1186/1471-2474-14-27

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