Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels

Steve S. Ho, Nina L. Vollmer, Motasem I. Refaat, Oju Jeon, Eben Alsberg, Mark A Lee, Jonathan K Leach

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair.

Original languageEnglish (US)
JournalAdvanced healthcare materials
DOIs
StateAccepted/In press - 2016

Fingerprint

Bone Morphogenetic Protein 2
Hydrogels
Alginate
Stem cells
Mesenchymal Stromal Cells
Osteogenesis
Cell Survival
Bone
Proteins
Bone and Bones
Apoptosis
Defects
Cell death
Repair
Mesenchymal Stem Cell Transplantation
Bioluminescence
human BMP2 protein
alginic acid
Biocompatible Materials
Tissue

Keywords

  • Bone morphogenetic protein-2
  • Mesenchymal stem cell
  • Osteogenesis
  • Photocrosslinking
  • Survival

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

Cite this

Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels. / Ho, Steve S.; Vollmer, Nina L.; Refaat, Motasem I.; Jeon, Oju; Alsberg, Eben; Lee, Mark A; Leach, Jonathan K.

In: Advanced healthcare materials, 2016.

Research output: Contribution to journalArticle

@article{f990aa7c8833491d9a22c9db91320123,
title = "Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels",
abstract = "There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100{\%} union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair.",
keywords = "Bone morphogenetic protein-2, Mesenchymal stem cell, Osteogenesis, Photocrosslinking, Survival",
author = "Ho, {Steve S.} and Vollmer, {Nina L.} and Refaat, {Motasem I.} and Oju Jeon and Eben Alsberg and Lee, {Mark A} and Leach, {Jonathan K}",
year = "2016",
doi = "10.1002/adhm.201600461",
language = "English (US)",
journal = "Advanced healthcare materials",
issn = "2192-2640",
publisher = "John Wiley and Sons Ltd",

}

TY - JOUR

T1 - Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels

AU - Ho, Steve S.

AU - Vollmer, Nina L.

AU - Refaat, Motasem I.

AU - Jeon, Oju

AU - Alsberg, Eben

AU - Lee, Mark A

AU - Leach, Jonathan K

PY - 2016

Y1 - 2016

N2 - There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair.

AB - There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair.

KW - Bone morphogenetic protein-2

KW - Mesenchymal stem cell

KW - Osteogenesis

KW - Photocrosslinking

KW - Survival

UR - http://www.scopus.com/inward/record.url?scp=84984680201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84984680201&partnerID=8YFLogxK

U2 - 10.1002/adhm.201600461

DO - 10.1002/adhm.201600461

M3 - Article

C2 - 27581621

AN - SCOPUS:84991070350

JO - Advanced healthcare materials

JF - Advanced healthcare materials

SN - 2192-2640

ER -