Premium
Injectable chitosan‐platelet‐rich plasma implants to promote tissue regeneration: in vitro properties, in vivo residence, degradation, cell recruitment and vascularization
Author(s) -
Chevrier A.,
Darras V.,
Picard G.,
Nelea M.,
Veilleux D.,
Lavertu M.,
Hoemann C.D.,
Buschman M.D.
Publication year - 2018
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2403
Subject(s) - regeneration (biology) , in vivo , chitosan , in vitro , platelet rich plasma , biomedical engineering , chemistry , degradation (telecommunications) , microbiology and biotechnology , platelet , medicine , biology , immunology , engineering , biochemistry , telecommunications
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 ( M n ), 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 M n , 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 M n and 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 M n , and occurred only with medium M n chitosan. 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.