title: Injectable chitosan-platelet-rich plasma implants to promote tissue regeneration: in vitro properties, in vivo residence, degradation, cell recruitment and vascularization.
abstract: The purpose of this study was to develop freeze-dried chitosan formulations that can be solubilized in platelet-rich plasma (PRP) to form injectable implants for tissue repair. A systematic approach to adjust formulation parameters, including chitosan number average molar mass (Mn), chitosan concentration and lyoprotectant concentration, was undertaken to identify compositions that would rapidly (< 1 min) and completely solubilize in PRP, would have paste-like handling properties upon solubilization and coagulate rapidly (< 5 min) to form solid chitosan-PRP hybrid implants that are stable and homogenous. Freeze-dried cakes containing calcium chloride, as well as distinct chitosan Mn, chitosan concentration and lyoprotectant concentration, were prepared. PRP was used to solubilize the freeze-dried cakes and assess in vitro and in vivo performance, the latter as dorsal subcutaneous injections into New Zealand White rabbits. Freeze-dried polymer formulations containing low and medium chitosan Mnand concentrations were rapidly and completely solubilized in PRP. The paste-like chitosan-PRP mixtures coagulated quickly to form solid chitosan-PRP hybrids, which retracted much less than PRP-only controls. Homogeneous dispersion of chitosan within the hybrid clots was strongly dependent on chitosan Mn, and occurred only with medium Mnchitosan. Chitosan-PRP hybrid clots were resident subcutaneously in vivo until at least 2 weeks while PRP controls were quickly degraded in one day. Compared to PRP alone, chitosan-PRP hybrids had much greater capacity to induce local cell recruitment accompanied by angiogenesis, suggesting a strong potential for their use in regenerative medicine. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Chemical Engineering Department, Polytechnique Montreal, Montreal, QC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Chevrier
authors.affiliation: Chemical Engineering Department, Polytechnique Montreal, Montreal, QC, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Darras
authors.affiliation: Chemical Engineering Department, Polytechnique Montreal, Montreal, QC, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Picard
authors.affiliation: Chemical Engineering Department, Polytechnique Montreal, Montreal, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Nelea
authors.affiliation: Biomedical Engineering Institute, Polytechnique Montreal, Montreal, QC, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Veilleux
authors.affiliation: Chemical Engineering Department, Polytechnique Montreal, Montreal, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Lavertu
authors.affiliation: Chemical Engineering Department, Polytechnique Montreal, Montreal, QC, Canada.|Biomedical Engineering Institute, Polytechnique Montreal, Montreal, QC, Canada.
authors.forename: C D
authors.initials: CD
authors.lastname: Hoemann
authors.affiliation: Chemical Engineering Department, Polytechnique Montreal, Montreal, QC, Canada.|Biomedical Engineering Institute, Polytechnique Montreal, Montreal, QC, Canada.
authors.forename: M D
authors.initials: MD
authors.lastname: Buschman
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D005612:Freeze Drying; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020007:Implants, Experimental; D007267:Injections; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D053657:Platelet-Rich Plasma / Q000378:metabolism*; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects*; D012995:Solubility
chemical_list: D048271:Chitosan
keywords: biocompatibility; chitosan; injectable implants; platelet-rich plasma; tissue repair