Scaffold-guided subchondral bone repair: implication of neutrophils and alternatively activated arginase-1+ macrophages.
BACKGROUND
Microfracture and drilling elicit a cartilage repair whose quality depends on subchondral bone repair. Alternatively activated (AA) macrophages express arginase-1, release angiogenic factors, and could be potential mediators of trabecular bone repair.


OBJECTIVE
Chitosan-glycerol phosphate (GP)/blood implants elicit arginase-1+ macrophages in vivo through neutrophil-dependent mechanisms and improve trabecular bone repair of drilled defects compared with drilling alone.


METHODS
Controlled laboratory study.


METHODS
Bilateral trochlear cartilage defects were created in 15 rabbits, microdrilled, and treated or not with chitosan-GP/blood implant to analyze AA macrophages, CD-31+ blood vessels, bone, and cartilage repair after 1, 2, or 8 weeks. Neutrophil and macrophage chemotaxis to rabbit subcutaneous implants of autologous blood and chitosan-GP (+/-blood) was quantified at 1 or 7 days. In vitro, sera from human chitosan-GP/blood and whole blood clots cultured at 37 degrees C were analyzed by proteomics and neutrophil chemotaxis assays.


RESULTS
Chitosan-GP/blood clots and whole blood clots released a similar profile of chemotactic factors (PDGF-BB, IL-8/CXCL8, MCP-1/CCL2, and no IL-1beta or IL-6), although chitosan clot sera attracted more neutrophils in vitro. Subcutaneous chitosan-GP (+/-blood) implants attracted more neutrophils (P < .001) and AA macrophages than whole blood clots in vivo. In repairing subchondral drill holes, chitosan-GP/blood implant attracted more AA macrophages at 1 and 2 weeks and more blood vessels at 2 weeks compared with drilled controls. Treatment elicited a more complete woven bone repair at 8 weeks than controls (P = .0011) with a more uniform, integrated collagen type II+ cartilage repair tissue.


CONCLUSIONS
AA macrophages may play a role in the regeneration of subchondral bone, and chitosan-GP can attract and transiently accumulate these cells in the repair tissue. The resulting improved subchondral repair could be advantageous toward enhancing integration of a restored chondral surface to the subchondral bone.
Hoemann
Caroline D
CD
Department of Chemical Engineering, Ecole Polytechnique, Montréal, QC, H3C 3A7 Canada. caroline.hoemann@polymtl.ca
Chen
Gaoping
G
Marchand
Catherine
C
Tran-Khanh
Nicolas
N
Thibault
Marc
M
Chevrier
Anik
A
Sun
Jun
J
Shive
Matthew S
MS
Fernandes
Maria J G
MJ
Poubelle
Patrice E
PE
Centola
Michael
M
El-Gabalawy
Hani
H
D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001119:Arginase / Q000378:metabolism; D054544:Arthroplasty, Subchondral; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D002357:Cartilage Diseases / Q000188:drug therapy* / Q000601:surgery*; D002358:Cartilage, Articular / Q000502:physiology*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis; D002630:Chemotactic Factors / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D048271:Chitosan / Q000494:pharmacology / Q000627:therapeutic use; D020219:Chondrogenesis / Q000187:drug effects*; D003029:Coagulants / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005990:Glycerol / Q000494:pharmacology / Q000627:therapeutic use; D048091:Guided Tissue Regeneration; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008264:Macrophages / Q000201:enzymology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D009504:Neutrophils / Q000502:physiology*; D010710:Phosphates / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D054457:Tissue Scaffolds; D055815:Young Adult
D043925:Angiogenesis Inducing Agents; D018932:Chemokine CCL2; D018925:Chemokines; D002630:Chemotactic Factors; D003029:Coagulants; D016209:Interleukin-8; D010710:Phosphates; D048271:Chitosan; D001119:Arginase; D005990:Glycerol