Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation

Cynthia Huang, Anusuya Das, Daniel Barker, Sunil Tholpady, Tiffany Wang, Quanjun Cui, Roy Ogle, Edward Botchwey

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and micro-circulation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm3, respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL® ) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

Original languageEnglish (US)
Pages (from-to)553-566
Number of pages14
JournalCell and Tissue Research
Volume347
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

Fingerprint

Osteogenesis
Allografts
Bone and Bones
Bone Development
Fingolimod Hydrochloride
Stem Cells
Lysosphingolipid Receptors
Blood Vessels
High Pressure Liquid Chromatography
Tomography
Wounds and Injuries

Keywords

  • Angiogenesis
  • Bone tissue engineering
  • Drug delivery
  • Massive allograft
  • Osseointegration

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Histology

Cite this

Huang, C., Das, A., Barker, D., Tholpady, S., Wang, T., Cui, Q., ... Botchwey, E. (2012). Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation. Cell and Tissue Research, 347(3), 553-566. https://doi.org/10.1007/s00441-011-1217-3

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation. / Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy; Botchwey, Edward.

In: Cell and Tissue Research, Vol. 347, No. 3, 03.2012, p. 553-566.

Research output: Contribution to journalArticle

Huang, C, Das, A, Barker, D, Tholpady, S, Wang, T, Cui, Q, Ogle, R & Botchwey, E 2012, 'Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation', Cell and Tissue Research, vol. 347, no. 3, pp. 553-566. https://doi.org/10.1007/s00441-011-1217-3
Huang, Cynthia ; Das, Anusuya ; Barker, Daniel ; Tholpady, Sunil ; Wang, Tiffany ; Cui, Quanjun ; Ogle, Roy ; Botchwey, Edward. / Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation. In: Cell and Tissue Research. 2012 ; Vol. 347, No. 3. pp. 553-566.
@article{1e5d1ea5db5743a9baf3029d6ee055c8,
title = "Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation",
abstract = "Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and micro-circulation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50{\%} loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm3, respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL{\circledR} ) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.",
keywords = "Angiogenesis, Bone tissue engineering, Drug delivery, Massive allograft, Osseointegration",
author = "Cynthia Huang and Anusuya Das and Daniel Barker and Sunil Tholpady and Tiffany Wang and Quanjun Cui and Roy Ogle and Edward Botchwey",
year = "2012",
month = "3",
doi = "10.1007/s00441-011-1217-3",
language = "English (US)",
volume = "347",
pages = "553--566",
journal = "Cell and Tissue Research",
issn = "0302-766X",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation

AU - Huang, Cynthia

AU - Das, Anusuya

AU - Barker, Daniel

AU - Tholpady, Sunil

AU - Wang, Tiffany

AU - Cui, Quanjun

AU - Ogle, Roy

AU - Botchwey, Edward

PY - 2012/3

Y1 - 2012/3

N2 - Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and micro-circulation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm3, respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL® ) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

AB - Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and micro-circulation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm3, respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL® ) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

KW - Angiogenesis

KW - Bone tissue engineering

KW - Drug delivery

KW - Massive allograft

KW - Osseointegration

UR - http://www.scopus.com/inward/record.url?scp=84860389144&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860389144&partnerID=8YFLogxK

U2 - 10.1007/s00441-011-1217-3

DO - 10.1007/s00441-011-1217-3

M3 - Article

C2 - 21863314

AN - SCOPUS:84860389144

VL - 347

SP - 553

EP - 566

JO - Cell and Tissue Research

JF - Cell and Tissue Research

SN - 0302-766X

IS - 3

ER -