TY - JOUR
T1 - “Ruffled border” formation on a CaP-free substrate
T2 - A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over
AU - Merolli, Antonio
AU - Fung, Stephanie
AU - Murthy, N. Sanjeeva
AU - Pashuck, E. Thomas
AU - Mao, Yong
AU - Wu, Xiaohuan
AU - Steele, Joseph A.M.
AU - Martin, Daniel
AU - Moghe, Prabhas V.
AU - Bromage, Timothy
AU - Kohn, Joachim
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Osteoclasts are large multinucleated giant cells that actively resorb bone during the physiological bone turnover (BTO), which is the continuous cycle of bone resorption (by osteoclasts) followed by new bone formation (by osteoblasts). Osteoclasts secrete chemotactic signals to recruit cells for regeneration of vasculature and bone. We hypothesize that a biomaterial that attracts osteoclasts and re-establishes BTO will induce a better healing response than currently used bone graft materials. While the majority of bone regeneration efforts have focused on maximizing bone deposition, the novelty in this approach is the focus on stimulating osteoclastic resorption as the starter for BTO and its concurrent new vascularized bone formation. A biodegradable tyrosine-derived polycarbonate, E1001(1k), was chosen as the polymer base due to its ability to support bone regeneration in vivo. The polymer was functionalized with a RGD peptide or collagen I, or blended with β-tricalcium phosphate. Osteoclast attachment and early stages of active resorption were observed on all substrates. The transparency of E1001(1k) in combination with high resolution confocal imaging enabled visualization of morphological features of osteoclast activation such as the formation of the “actin ring” and the “ruffled border”, which previously required destructive forms of imaging such as transmission electron microscopy. The significance of these results is twofold: (1) E1001(1k) is suitable for osteoclast attachment and supports osteoclast maturation, making it a base polymer that can be further modified to optimize stimulation of BTO and (2) the transparency of this polymer makes it a suitable analytical tool for studying osteoclast behavior. [Figure not available: see fulltext.].
AB - Osteoclasts are large multinucleated giant cells that actively resorb bone during the physiological bone turnover (BTO), which is the continuous cycle of bone resorption (by osteoclasts) followed by new bone formation (by osteoblasts). Osteoclasts secrete chemotactic signals to recruit cells for regeneration of vasculature and bone. We hypothesize that a biomaterial that attracts osteoclasts and re-establishes BTO will induce a better healing response than currently used bone graft materials. While the majority of bone regeneration efforts have focused on maximizing bone deposition, the novelty in this approach is the focus on stimulating osteoclastic resorption as the starter for BTO and its concurrent new vascularized bone formation. A biodegradable tyrosine-derived polycarbonate, E1001(1k), was chosen as the polymer base due to its ability to support bone regeneration in vivo. The polymer was functionalized with a RGD peptide or collagen I, or blended with β-tricalcium phosphate. Osteoclast attachment and early stages of active resorption were observed on all substrates. The transparency of E1001(1k) in combination with high resolution confocal imaging enabled visualization of morphological features of osteoclast activation such as the formation of the “actin ring” and the “ruffled border”, which previously required destructive forms of imaging such as transmission electron microscopy. The significance of these results is twofold: (1) E1001(1k) is suitable for osteoclast attachment and supports osteoclast maturation, making it a base polymer that can be further modified to optimize stimulation of BTO and (2) the transparency of this polymer makes it a suitable analytical tool for studying osteoclast behavior. [Figure not available: see fulltext.].
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U2 - 10.1007/s10856-018-6046-4
DO - 10.1007/s10856-018-6046-4
M3 - Article
C2 - 29564568
AN - SCOPUS:85044301208
SN - 0957-4530
VL - 29
JO - Journal of Materials Science: Materials in Medicine
JF - Journal of Materials Science: Materials in Medicine
IS - 4
M1 - 38
ER -