Hyaluronic acid stimulates neovascularization during the regeneration of bone marrow after ablation.
Restoration of vasculature is a critical component for successful integration of implants in musculoskeletal tissue. Sodium hyaluronate (NaHY) has been used as a carrier for demineralized bone matrix (DBM). DBM is osteoinductive and osteoconductive, but whether NaHY by itself has an effect is not known. NaHY has been reported to promote neovascularization, suggesting it may increase neovasculature when used with DBM as well. To test this, we used a rat tibial marrow ablation model to assess neovascularization during bone formation and regeneration of marrow with different combinations of NaHY alone and NaHY+DBM. To assess neovascularization during normal healing, animals were euthanized at 3-, 6-, 14-, 21-, and 28-days post-ablation, and the vasculature perfused using a radio-opaque contrast agent. Vascular morphology was assessed using μCT and histology. Peak vessel volume within the marrow cavity was observed on day-14 post-ablation. Test materials were injected into the ablated marrow space as follows: (A) empty defect controls; (B) high MW (700-800 kDa) NaHY + heat inactivated DBM; (C) DBM in PBS; (D) low MW NaHY (35 kDa) + DBM; (E) high MW NaHY + DBM; (F) D:E 50:50; (G) low MW NaHY; (H) high MW NaHY; and (I) G:H 50:50. Neovascularization varied with bone substitute formulation. μCT results revealed that addition of NaHY resulted in an increase in vessel number compared to empty defects. Total blood vessel volume in all NaHY only groups were similar to DBM alone. Histomorphometry of sagittal sections showed that all three formulations of NaHY increased blood vessel number within the marrow cavity, confirming that NaHY promotes neovascularization.
Parker H Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
Andrew L
AL
Raines
Moonhae
M
Sunwoo
Arthur A
AA
Gertzman
Kipling
K
Thacker
Robert E
RE
Guldberg
Zvi
Z
Schwartz
Barbara D
BD
Boyan
D055011:Ablation Techniques; D000818:Animals; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000601:surgery*; D001857:Bone Matrix / Q000187:drug effects / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D005240:Feasibility Studies; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D013977:Tibia / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D055114:X-Ray Microtomography
D006820:Hyaluronic Acid
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