Three-Dimension-Printed Porous Poly(Propylene Fumarate) Scaffolds with Delayed rhBMP-2 Release for Anterior Cruciate Ligament Graft Fixation

Joshua Alan Parry, Maurits G.L. Olthof, Kristen L. Shogren, Mahrokh Dadsetan, Andre J van Wijnen, Michael J Yaszemski, Sanjeev Kakar

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Anterior cruciate ligament (ACL) ruptures reconstructed with tendon grafts are commonly fixed with bioabsorbable implants, which are frequently complicated by incomplete bone filling upon degradation. Bone regeneration after ACL reconstruction could be enhanced by utilizing tissue engineering techniques and three-dimensional (3D) printing to create a porous bioabsorbable scaffold with delayed delivery of recombinant-human bone morphogenetic protein 2 (rhBMP-2). The first aim of this study was to design a 3D poly(propylene fumarate) (PPF) porous scaffold that maintained suitable pullout strength for future testing in a rabbit ACL reconstruction model. Our second aim was to determine the release kinetics of rhBMP-2 from PPF scaffolds that utilized both calcium-phosphate coatings and growth factor delivery on microspheres, both of which have been shown to decrease the initial burst release of rhBMP-2 and increase bone regeneration. To determine the degree of scaffold porosity that maintained suitable pullout strength, tapered scaffolds were fabricated with increasing porosity (0%, 20%, 35%, and 44%) and pullout testing was performed in a cadaveric rabbit ACL reconstruction model. Scaffolds were coated with carbonate hydroxyapatite (synthetic bone mineral [SBM]), and radiolabeled rhBMP-2 was delivered in four different experimental groups as follows: Poly(lactic-co-glycolic acid) microspheres only, microspheres and collagen (50:50), collagen only, and saline solution only. rhBMP-2 release was measured at day 1, 2, 4, 8, 16, and 32. The microsphere delivery groups had a smaller burst release and released a smaller percentage of rhBMP-2 over the 32 days than the collagen and saline only groups. In conclusion, a porous bioabsorbable scaffold with suitable strength for a rabbit ACL reconstruction was developed. Combining a synthetic bone mineral coating with microspheres had an additive effect, decreasing the initial burst release and cumulative release of rhBMP-2. Future studies need to evaluate this scaffold's fixation strength and bone filling capabilities in vivo compared to traditional bioabsorbable implants.

Original languageEnglish (US)
Pages (from-to)359-365
Number of pages7
JournalTissue Engineering - Part A
Volume23
Issue number7-8
DOIs
StatePublished - Apr 1 2017

Fingerprint

Anterior Cruciate Ligament
Ligaments
Scaffolds (biology)
Grafts
Scaffolds
Polypropylenes
Bone
Microspheres
Anterior Cruciate Ligament Reconstruction
Proteins
Transplants
Absorbable Implants
Bone and Bones
Bone Regeneration
Collagen
Porosity
Rabbits
Minerals
Fumarates
Carbonates

Keywords

  • anterior cruciate ligament
  • bioabsorbable
  • microspheres
  • poly(propylene fumarate)
  • rhBMP-2

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Cite this

Three-Dimension-Printed Porous Poly(Propylene Fumarate) Scaffolds with Delayed rhBMP-2 Release for Anterior Cruciate Ligament Graft Fixation. / Parry, Joshua Alan; Olthof, Maurits G.L.; Shogren, Kristen L.; Dadsetan, Mahrokh; van Wijnen, Andre J; Yaszemski, Michael J; Kakar, Sanjeev.

In: Tissue Engineering - Part A, Vol. 23, No. 7-8, 01.04.2017, p. 359-365.

Research output: Contribution to journalArticle

Parry, Joshua Alan ; Olthof, Maurits G.L. ; Shogren, Kristen L. ; Dadsetan, Mahrokh ; van Wijnen, Andre J ; Yaszemski, Michael J ; Kakar, Sanjeev. / Three-Dimension-Printed Porous Poly(Propylene Fumarate) Scaffolds with Delayed rhBMP-2 Release for Anterior Cruciate Ligament Graft Fixation. In: Tissue Engineering - Part A. 2017 ; Vol. 23, No. 7-8. pp. 359-365.
@article{e020c818ffa548659969c59a4ff46cbd,
title = "Three-Dimension-Printed Porous Poly(Propylene Fumarate) Scaffolds with Delayed rhBMP-2 Release for Anterior Cruciate Ligament Graft Fixation",
abstract = "Anterior cruciate ligament (ACL) ruptures reconstructed with tendon grafts are commonly fixed with bioabsorbable implants, which are frequently complicated by incomplete bone filling upon degradation. Bone regeneration after ACL reconstruction could be enhanced by utilizing tissue engineering techniques and three-dimensional (3D) printing to create a porous bioabsorbable scaffold with delayed delivery of recombinant-human bone morphogenetic protein 2 (rhBMP-2). The first aim of this study was to design a 3D poly(propylene fumarate) (PPF) porous scaffold that maintained suitable pullout strength for future testing in a rabbit ACL reconstruction model. Our second aim was to determine the release kinetics of rhBMP-2 from PPF scaffolds that utilized both calcium-phosphate coatings and growth factor delivery on microspheres, both of which have been shown to decrease the initial burst release of rhBMP-2 and increase bone regeneration. To determine the degree of scaffold porosity that maintained suitable pullout strength, tapered scaffolds were fabricated with increasing porosity (0{\%}, 20{\%}, 35{\%}, and 44{\%}) and pullout testing was performed in a cadaveric rabbit ACL reconstruction model. Scaffolds were coated with carbonate hydroxyapatite (synthetic bone mineral [SBM]), and radiolabeled rhBMP-2 was delivered in four different experimental groups as follows: Poly(lactic-co-glycolic acid) microspheres only, microspheres and collagen (50:50), collagen only, and saline solution only. rhBMP-2 release was measured at day 1, 2, 4, 8, 16, and 32. The microsphere delivery groups had a smaller burst release and released a smaller percentage of rhBMP-2 over the 32 days than the collagen and saline only groups. In conclusion, a porous bioabsorbable scaffold with suitable strength for a rabbit ACL reconstruction was developed. Combining a synthetic bone mineral coating with microspheres had an additive effect, decreasing the initial burst release and cumulative release of rhBMP-2. Future studies need to evaluate this scaffold's fixation strength and bone filling capabilities in vivo compared to traditional bioabsorbable implants.",
keywords = "anterior cruciate ligament, bioabsorbable, microspheres, poly(propylene fumarate), rhBMP-2",
author = "Parry, {Joshua Alan} and Olthof, {Maurits G.L.} and Shogren, {Kristen L.} and Mahrokh Dadsetan and {van Wijnen}, {Andre J} and Yaszemski, {Michael J} and Sanjeev Kakar",
year = "2017",
month = "4",
day = "1",
doi = "10.1089/ten.tea.2016.0343",
language = "English (US)",
volume = "23",
pages = "359--365",
journal = "Tissue Engineering - Part A",
issn = "1937-3341",
publisher = "Mary Ann Liebert Inc.",
number = "7-8",

}

TY - JOUR

T1 - Three-Dimension-Printed Porous Poly(Propylene Fumarate) Scaffolds with Delayed rhBMP-2 Release for Anterior Cruciate Ligament Graft Fixation

AU - Parry, Joshua Alan

AU - Olthof, Maurits G.L.

AU - Shogren, Kristen L.

AU - Dadsetan, Mahrokh

AU - van Wijnen, Andre J

AU - Yaszemski, Michael J

AU - Kakar, Sanjeev

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Anterior cruciate ligament (ACL) ruptures reconstructed with tendon grafts are commonly fixed with bioabsorbable implants, which are frequently complicated by incomplete bone filling upon degradation. Bone regeneration after ACL reconstruction could be enhanced by utilizing tissue engineering techniques and three-dimensional (3D) printing to create a porous bioabsorbable scaffold with delayed delivery of recombinant-human bone morphogenetic protein 2 (rhBMP-2). The first aim of this study was to design a 3D poly(propylene fumarate) (PPF) porous scaffold that maintained suitable pullout strength for future testing in a rabbit ACL reconstruction model. Our second aim was to determine the release kinetics of rhBMP-2 from PPF scaffolds that utilized both calcium-phosphate coatings and growth factor delivery on microspheres, both of which have been shown to decrease the initial burst release of rhBMP-2 and increase bone regeneration. To determine the degree of scaffold porosity that maintained suitable pullout strength, tapered scaffolds were fabricated with increasing porosity (0%, 20%, 35%, and 44%) and pullout testing was performed in a cadaveric rabbit ACL reconstruction model. Scaffolds were coated with carbonate hydroxyapatite (synthetic bone mineral [SBM]), and radiolabeled rhBMP-2 was delivered in four different experimental groups as follows: Poly(lactic-co-glycolic acid) microspheres only, microspheres and collagen (50:50), collagen only, and saline solution only. rhBMP-2 release was measured at day 1, 2, 4, 8, 16, and 32. The microsphere delivery groups had a smaller burst release and released a smaller percentage of rhBMP-2 over the 32 days than the collagen and saline only groups. In conclusion, a porous bioabsorbable scaffold with suitable strength for a rabbit ACL reconstruction was developed. Combining a synthetic bone mineral coating with microspheres had an additive effect, decreasing the initial burst release and cumulative release of rhBMP-2. Future studies need to evaluate this scaffold's fixation strength and bone filling capabilities in vivo compared to traditional bioabsorbable implants.

AB - Anterior cruciate ligament (ACL) ruptures reconstructed with tendon grafts are commonly fixed with bioabsorbable implants, which are frequently complicated by incomplete bone filling upon degradation. Bone regeneration after ACL reconstruction could be enhanced by utilizing tissue engineering techniques and three-dimensional (3D) printing to create a porous bioabsorbable scaffold with delayed delivery of recombinant-human bone morphogenetic protein 2 (rhBMP-2). The first aim of this study was to design a 3D poly(propylene fumarate) (PPF) porous scaffold that maintained suitable pullout strength for future testing in a rabbit ACL reconstruction model. Our second aim was to determine the release kinetics of rhBMP-2 from PPF scaffolds that utilized both calcium-phosphate coatings and growth factor delivery on microspheres, both of which have been shown to decrease the initial burst release of rhBMP-2 and increase bone regeneration. To determine the degree of scaffold porosity that maintained suitable pullout strength, tapered scaffolds were fabricated with increasing porosity (0%, 20%, 35%, and 44%) and pullout testing was performed in a cadaveric rabbit ACL reconstruction model. Scaffolds were coated with carbonate hydroxyapatite (synthetic bone mineral [SBM]), and radiolabeled rhBMP-2 was delivered in four different experimental groups as follows: Poly(lactic-co-glycolic acid) microspheres only, microspheres and collagen (50:50), collagen only, and saline solution only. rhBMP-2 release was measured at day 1, 2, 4, 8, 16, and 32. The microsphere delivery groups had a smaller burst release and released a smaller percentage of rhBMP-2 over the 32 days than the collagen and saline only groups. In conclusion, a porous bioabsorbable scaffold with suitable strength for a rabbit ACL reconstruction was developed. Combining a synthetic bone mineral coating with microspheres had an additive effect, decreasing the initial burst release and cumulative release of rhBMP-2. Future studies need to evaluate this scaffold's fixation strength and bone filling capabilities in vivo compared to traditional bioabsorbable implants.

KW - anterior cruciate ligament

KW - bioabsorbable

KW - microspheres

KW - poly(propylene fumarate)

KW - rhBMP-2

UR - http://www.scopus.com/inward/record.url?scp=85018525546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018525546&partnerID=8YFLogxK

U2 - 10.1089/ten.tea.2016.0343

DO - 10.1089/ten.tea.2016.0343

M3 - Article

C2 - 28081675

AN - SCOPUS:85018525546

VL - 23

SP - 359

EP - 365

JO - Tissue Engineering - Part A

JF - Tissue Engineering - Part A

SN - 1937-3341

IS - 7-8

ER -