Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice

Samuel Herberg, Galina Kondrikova, Sudharsan Periyasamy Thandavan, R. Nicole Howie, Mohammed Elsayed Elsalanty, Lee Weiss, Phil Campbell, William D Hill, James J. Cray

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: A major problem in craniofacial surgery is non-healing bone defects. Autologous reconstruction remains the standard of care for these cases. Bone morphogenetic protein-2 (BMP-2) therapy has proven its clinical utility, although non-targeted adverse events occur due to the high milligram-level doses used. Ongoing efforts explore the use of different growth factors, cytokines, or chemokines, as well as co-therapy to augment healing. Methods: Here we utilize inkjet-based biopatterning to load acellular DermaMatrix delivery matrices with nanogram-level doses of BMP-2, stromal cell-derived factor-1β (SDF-1β), transforming growth factor-β1 (TGF-β1), or co-therapies thereof. We tested the hypothesis that bioprinted SDF-1β co-delivery enhances BMP-2 and TGF-β1-driven osteogenesis both in-vitro and in-vivo using a mouse calvarial critical size defect (CSD) model. Results: Our data showed that BMP-2 bioprinted in low-doses induced significant new bone formation by four weeks post-operation. TGF-β1 was less effective compared to BMP-2, and SDF-1β therapy did not enhance osteogenesis above control levels. However, co-delivery of BMP-2. +. SDF-1β was shown to augment BMP-2-induced bone formation compared to BMP-2 alone. In contrast, co-delivery of TGF-β1. +. SDF-1β decreased bone healing compared to TGF-β1 alone. This was further confirmed in vitro by osteogenic differentiation studies using MC3T3-E1 pre-osteoblasts. Conclusions: Our data indicates that sustained release delivery of a low-dose growth factor therapy using biopatterning technology can aid in healing CSD injuries. SDF-1β augments the ability for BMP-2 to drive healing, a result confirmed in vivo and in vitro; however, because SDF-1β is detrimental to TGF-β1-driven osteogenesis, its effect on osteogenesis is not universal.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalBone
Volume67
DOIs
StatePublished - Jan 1 2014

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Chemokine CXCL12
Bone Morphogenetic Protein 2
Transforming Growth Factors
Osteogenesis
Bone and Bones
Intercellular Signaling Peptides and Proteins
Therapeutics
Standard of Care
Osteoblasts
Chemokines
Cytokines
Technology

Keywords

  • BMP-2
  • Biopatterning
  • Bone
  • Healing
  • SDF-1β
  • TGF-β1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Herberg, S., Kondrikova, G., Periyasamy Thandavan, S., Howie, R. N., Elsalanty, M. E., Weiss, L., ... Cray, J. J. (2014). Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice. Bone, 67, 95-103. https://doi.org/10.1016/j.bone.2014.07.007

Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice. / Herberg, Samuel; Kondrikova, Galina; Periyasamy Thandavan, Sudharsan; Howie, R. Nicole; Elsalanty, Mohammed Elsayed; Weiss, Lee; Campbell, Phil; Hill, William D; Cray, James J.

In: Bone, Vol. 67, 01.01.2014, p. 95-103.

Research output: Contribution to journalArticle

Herberg, S, Kondrikova, G, Periyasamy Thandavan, S, Howie, RN, Elsalanty, ME, Weiss, L, Campbell, P, Hill, WD & Cray, JJ 2014, 'Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice', Bone, vol. 67, pp. 95-103. https://doi.org/10.1016/j.bone.2014.07.007
Herberg, Samuel ; Kondrikova, Galina ; Periyasamy Thandavan, Sudharsan ; Howie, R. Nicole ; Elsalanty, Mohammed Elsayed ; Weiss, Lee ; Campbell, Phil ; Hill, William D ; Cray, James J. / Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice. In: Bone. 2014 ; Vol. 67. pp. 95-103.
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abstract = "Background: A major problem in craniofacial surgery is non-healing bone defects. Autologous reconstruction remains the standard of care for these cases. Bone morphogenetic protein-2 (BMP-2) therapy has proven its clinical utility, although non-targeted adverse events occur due to the high milligram-level doses used. Ongoing efforts explore the use of different growth factors, cytokines, or chemokines, as well as co-therapy to augment healing. Methods: Here we utilize inkjet-based biopatterning to load acellular DermaMatrix delivery matrices with nanogram-level doses of BMP-2, stromal cell-derived factor-1β (SDF-1β), transforming growth factor-β1 (TGF-β1), or co-therapies thereof. We tested the hypothesis that bioprinted SDF-1β co-delivery enhances BMP-2 and TGF-β1-driven osteogenesis both in-vitro and in-vivo using a mouse calvarial critical size defect (CSD) model. Results: Our data showed that BMP-2 bioprinted in low-doses induced significant new bone formation by four weeks post-operation. TGF-β1 was less effective compared to BMP-2, and SDF-1β therapy did not enhance osteogenesis above control levels. However, co-delivery of BMP-2. +. SDF-1β was shown to augment BMP-2-induced bone formation compared to BMP-2 alone. In contrast, co-delivery of TGF-β1. +. SDF-1β decreased bone healing compared to TGF-β1 alone. This was further confirmed in vitro by osteogenic differentiation studies using MC3T3-E1 pre-osteoblasts. Conclusions: Our data indicates that sustained release delivery of a low-dose growth factor therapy using biopatterning technology can aid in healing CSD injuries. SDF-1β augments the ability for BMP-2 to drive healing, a result confirmed in vivo and in vitro; however, because SDF-1β is detrimental to TGF-β1-driven osteogenesis, its effect on osteogenesis is not universal.",
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AU - Howie, R. Nicole

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