“Ruffled border” formation on a CaP-free substrate

A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over

Antonio Merolli, Stephanie Fung, N. Sanjeeva Murthy, E. Thomas Pashuck, Yong Mao, Xiaohuan Wu, Joseph A.M. Steele, Daniel Martin, Prabhas V. Moghe, Timothy Bromage, Joachim Kohn

Research output: Contribution to journalArticle

Abstract

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.].

Original languageEnglish (US)
Article number38
JournalJournal of Materials Science: Materials in Medicine
Volume29
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Osteoclasts
Grafts
Bone
Transplants
Bone and Bones
Substrates
Bone Remodeling
Bone Regeneration
Polymers
polycarbonate
Osteogenesis
Transparency
Biocompatible Materials
Giant Cells
Bone Resorption
Osteoblasts
Transmission Electron Microscopy
Imaging techniques
Tyrosine
Actins

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

Cite this

“Ruffled border” formation on a CaP-free substrate : A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over. / Merolli, Antonio; Fung, Stephanie; Murthy, N. Sanjeeva; Pashuck, E. Thomas; Mao, Yong; Wu, Xiaohuan; Steele, Joseph A.M.; Martin, Daniel; Moghe, Prabhas V.; Bromage, Timothy; Kohn, Joachim.

In: Journal of Materials Science: Materials in Medicine, Vol. 29, No. 4, 38, 01.04.2018.

Research output: Contribution to journalArticle

Merolli, Antonio ; Fung, Stephanie ; Murthy, N. Sanjeeva ; Pashuck, E. Thomas ; Mao, Yong ; Wu, Xiaohuan ; Steele, Joseph A.M. ; Martin, Daniel ; Moghe, Prabhas V. ; Bromage, Timothy ; Kohn, Joachim. / “Ruffled border” formation on a CaP-free substrate : A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over. In: Journal of Materials Science: Materials in Medicine. 2018 ; Vol. 29, No. 4.
@article{4ff3ced4deab49ec9189ab355a2a8741,
title = "“Ruffled border” formation on a CaP-free substrate: A first step towards osteoclast-recruiting bone-grafts materials able to re-establish bone turn-over",
abstract = "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.].",
author = "Antonio Merolli and Stephanie Fung and Murthy, {N. Sanjeeva} and Pashuck, {E. Thomas} and Yong Mao and Xiaohuan Wu and Steele, {Joseph A.M.} and Daniel Martin and Moghe, {Prabhas V.} and Timothy Bromage and Joachim Kohn",
year = "2018",
month = "4",
day = "1",
doi = "10.1007/s10856-018-6046-4",
language = "English (US)",
volume = "29",
journal = "Journal of Materials Science: Materials in Medicine",
issn = "0957-4530",
publisher = "Springer Netherlands",
number = "4",

}

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

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.].

UR - http://www.scopus.com/inward/record.url?scp=85044301208&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044301208&partnerID=8YFLogxK

U2 - 10.1007/s10856-018-6046-4

DO - 10.1007/s10856-018-6046-4

M3 - Article

VL - 29

JO - Journal of Materials Science: Materials in Medicine

JF - Journal of Materials Science: Materials in Medicine

SN - 0957-4530

IS - 4

M1 - 38

ER -