Alginate hydrogels containing cell-interactive beads for bone formation

Archana Bhat, Allison I. Hoch, Martin L. Decaris, Jonathan K Leach

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Alginate hydrogels containing cell-instructive cues are the subject of intense interest for their use as cell carriers in bone tissue engineering. Peptides and proteins are chemically grafted onto these hydrophilic materials to facilitate adhesion and direct phenotype of entrapped cells. However, the presentation of a single or small number of peptides does not represent the complexity of the native extracellular matrix (ECM) of bony tissues. Mesenchymal stem cells (MSCs) secrete ECM that can be harvested and deposited on various substrata to promote osteogenic differentiation. In this study, we hypothesized that the presentation of engineered cell-secreted ECM on microbeads suspended in alginate hydrogels would promote cell adhesion and enhance osteogenic differentiation of undifferentiated MSCs without chemical incorporation of cell-adhesive peptides. Human MSCs entrapped in alginate hydrogels loaded with ECM-coated beads showed increased interaction with beads, when compared with cells suspended in hydrogels containing uncoated blank (BLK) beads. MSCs entrapped in ECM gels exhibited increased alkaline phosphatase (ALP) activity and expression of osteogenic genes in vitro compared with hydrogels modified with arginine-glycine- aspartic acid (RGD)-containing peptides. Transplantation of MSCs into an ectopic site resulted in significant increases in blood vessel density for ECM hydrogels when compared with the BLK or RGD gels. Furthermore, we observed comparable levels of bone formation at 6 wk with ECM and RGD hydrogels. These findings demonstrate that engineered ECM can be deployed in a minimally invasive manner to direct the formation of bony tissue. This strategy may provide an alternative to the engraftment of proteins or peptides onto the polymer backbone of hydrogels for directing cellular behavior.-Bhat, A., Hoch, A. I., Decaris, M. L., Leach, J. K. Alginate hydrogels containing cell-interactive beads for bone formation.

Original languageEnglish (US)
Pages (from-to)4844-4852
Number of pages9
JournalFASEB Journal
Volume27
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Hydrogels
Osteogenesis
Bone
Extracellular Matrix
Stem cells
Mesenchymal Stromal Cells
Peptides
Gels
Mesenchymal Stem Cell Transplantation
Tissue
alginic acid
Levamisole
Cell adhesion
Blood vessels
Tissue Engineering
Microspheres
Tissue engineering
Aspartic Acid
Cell Adhesion
Adhesives

Keywords

  • Adhesion ligands
  • Extracellular matrix
  • Mesenchymal stem cell
  • Osteogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Bhat, A., Hoch, A. I., Decaris, M. L., & Leach, J. K. (2013). Alginate hydrogels containing cell-interactive beads for bone formation. FASEB Journal, 27(12), 4844-4852. https://doi.org/10.1096/fj.12-213611

Alginate hydrogels containing cell-interactive beads for bone formation. / Bhat, Archana; Hoch, Allison I.; Decaris, Martin L.; Leach, Jonathan K.

In: FASEB Journal, Vol. 27, No. 12, 12.2013, p. 4844-4852.

Research output: Contribution to journalArticle

Bhat, A, Hoch, AI, Decaris, ML & Leach, JK 2013, 'Alginate hydrogels containing cell-interactive beads for bone formation', FASEB Journal, vol. 27, no. 12, pp. 4844-4852. https://doi.org/10.1096/fj.12-213611
Bhat, Archana ; Hoch, Allison I. ; Decaris, Martin L. ; Leach, Jonathan K. / Alginate hydrogels containing cell-interactive beads for bone formation. In: FASEB Journal. 2013 ; Vol. 27, No. 12. pp. 4844-4852.
@article{712c2138b60b487195cd1a54a4c83a00,
title = "Alginate hydrogels containing cell-interactive beads for bone formation",
abstract = "Alginate hydrogels containing cell-instructive cues are the subject of intense interest for their use as cell carriers in bone tissue engineering. Peptides and proteins are chemically grafted onto these hydrophilic materials to facilitate adhesion and direct phenotype of entrapped cells. However, the presentation of a single or small number of peptides does not represent the complexity of the native extracellular matrix (ECM) of bony tissues. Mesenchymal stem cells (MSCs) secrete ECM that can be harvested and deposited on various substrata to promote osteogenic differentiation. In this study, we hypothesized that the presentation of engineered cell-secreted ECM on microbeads suspended in alginate hydrogels would promote cell adhesion and enhance osteogenic differentiation of undifferentiated MSCs without chemical incorporation of cell-adhesive peptides. Human MSCs entrapped in alginate hydrogels loaded with ECM-coated beads showed increased interaction with beads, when compared with cells suspended in hydrogels containing uncoated blank (BLK) beads. MSCs entrapped in ECM gels exhibited increased alkaline phosphatase (ALP) activity and expression of osteogenic genes in vitro compared with hydrogels modified with arginine-glycine- aspartic acid (RGD)-containing peptides. Transplantation of MSCs into an ectopic site resulted in significant increases in blood vessel density for ECM hydrogels when compared with the BLK or RGD gels. Furthermore, we observed comparable levels of bone formation at 6 wk with ECM and RGD hydrogels. These findings demonstrate that engineered ECM can be deployed in a minimally invasive manner to direct the formation of bony tissue. This strategy may provide an alternative to the engraftment of proteins or peptides onto the polymer backbone of hydrogels for directing cellular behavior.-Bhat, A., Hoch, A. I., Decaris, M. L., Leach, J. K. Alginate hydrogels containing cell-interactive beads for bone formation.",
keywords = "Adhesion ligands, Extracellular matrix, Mesenchymal stem cell, Osteogenesis",
author = "Archana Bhat and Hoch, {Allison I.} and Decaris, {Martin L.} and Leach, {Jonathan K}",
year = "2013",
month = "12",
doi = "10.1096/fj.12-213611",
language = "English (US)",
volume = "27",
pages = "4844--4852",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "12",

}

TY - JOUR

T1 - Alginate hydrogels containing cell-interactive beads for bone formation

AU - Bhat, Archana

AU - Hoch, Allison I.

AU - Decaris, Martin L.

AU - Leach, Jonathan K

PY - 2013/12

Y1 - 2013/12

N2 - Alginate hydrogels containing cell-instructive cues are the subject of intense interest for their use as cell carriers in bone tissue engineering. Peptides and proteins are chemically grafted onto these hydrophilic materials to facilitate adhesion and direct phenotype of entrapped cells. However, the presentation of a single or small number of peptides does not represent the complexity of the native extracellular matrix (ECM) of bony tissues. Mesenchymal stem cells (MSCs) secrete ECM that can be harvested and deposited on various substrata to promote osteogenic differentiation. In this study, we hypothesized that the presentation of engineered cell-secreted ECM on microbeads suspended in alginate hydrogels would promote cell adhesion and enhance osteogenic differentiation of undifferentiated MSCs without chemical incorporation of cell-adhesive peptides. Human MSCs entrapped in alginate hydrogels loaded with ECM-coated beads showed increased interaction with beads, when compared with cells suspended in hydrogels containing uncoated blank (BLK) beads. MSCs entrapped in ECM gels exhibited increased alkaline phosphatase (ALP) activity and expression of osteogenic genes in vitro compared with hydrogels modified with arginine-glycine- aspartic acid (RGD)-containing peptides. Transplantation of MSCs into an ectopic site resulted in significant increases in blood vessel density for ECM hydrogels when compared with the BLK or RGD gels. Furthermore, we observed comparable levels of bone formation at 6 wk with ECM and RGD hydrogels. These findings demonstrate that engineered ECM can be deployed in a minimally invasive manner to direct the formation of bony tissue. This strategy may provide an alternative to the engraftment of proteins or peptides onto the polymer backbone of hydrogels for directing cellular behavior.-Bhat, A., Hoch, A. I., Decaris, M. L., Leach, J. K. Alginate hydrogels containing cell-interactive beads for bone formation.

AB - Alginate hydrogels containing cell-instructive cues are the subject of intense interest for their use as cell carriers in bone tissue engineering. Peptides and proteins are chemically grafted onto these hydrophilic materials to facilitate adhesion and direct phenotype of entrapped cells. However, the presentation of a single or small number of peptides does not represent the complexity of the native extracellular matrix (ECM) of bony tissues. Mesenchymal stem cells (MSCs) secrete ECM that can be harvested and deposited on various substrata to promote osteogenic differentiation. In this study, we hypothesized that the presentation of engineered cell-secreted ECM on microbeads suspended in alginate hydrogels would promote cell adhesion and enhance osteogenic differentiation of undifferentiated MSCs without chemical incorporation of cell-adhesive peptides. Human MSCs entrapped in alginate hydrogels loaded with ECM-coated beads showed increased interaction with beads, when compared with cells suspended in hydrogels containing uncoated blank (BLK) beads. MSCs entrapped in ECM gels exhibited increased alkaline phosphatase (ALP) activity and expression of osteogenic genes in vitro compared with hydrogels modified with arginine-glycine- aspartic acid (RGD)-containing peptides. Transplantation of MSCs into an ectopic site resulted in significant increases in blood vessel density for ECM hydrogels when compared with the BLK or RGD gels. Furthermore, we observed comparable levels of bone formation at 6 wk with ECM and RGD hydrogels. These findings demonstrate that engineered ECM can be deployed in a minimally invasive manner to direct the formation of bony tissue. This strategy may provide an alternative to the engraftment of proteins or peptides onto the polymer backbone of hydrogels for directing cellular behavior.-Bhat, A., Hoch, A. I., Decaris, M. L., Leach, J. K. Alginate hydrogels containing cell-interactive beads for bone formation.

KW - Adhesion ligands

KW - Extracellular matrix

KW - Mesenchymal stem cell

KW - Osteogenesis

UR - http://www.scopus.com/inward/record.url?scp=84890515192&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890515192&partnerID=8YFLogxK

U2 - 10.1096/fj.12-213611

DO - 10.1096/fj.12-213611

M3 - Article

C2 - 24005905

AN - SCOPUS:84890515192

VL - 27

SP - 4844

EP - 4852

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 12

ER -