Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Long-term response to a bioactive biphasic biomaterial in the femoral neck of osteoporotic rats

Raina, Deepak Bushan LU ; Širka, Aurimas ; Qayoom, Irfan ; Teotia, Arun Kumar ; Liu, Yang LU ; Tarasevicius, Sarunas LU ; Tanner, Kathleen Elizabeth ; Isaksson, Hanna LU orcid ; Kumar, Ashok LU and Tägil, Magnus LU , et al. (2020) In Tissue Engineering - Part A 26(19-20). p.1042-1051
Abstract

Osteoporosis often leads to fragility fractures of the hip, resulting in impaired quality of life and increased mortality. Augmenting the proximal femur could be an attractive option for prevention of fracture or fixation device failure. We describe a tissue engineering based strategy to enhance long-term bone formation in the femoral neck of osteoporotic rats by locally delivering bioactive molecules; recombinant human bone morphogenic protein-2 (rhBMP-2), and zoledronic acid (ZA) by using a calcium sulfate/ hydroxyapatite (CaS/HA) biomaterial. A defect was created by reaming the femoral neck canal of osteoporotic (OVX) rats and they were treated as follows: G1. Empty, G2. CaS/HA, G3. CaS/HA+Systemic ZA, G4. CaS/HA+Local ZA, and G5.... (More)

Osteoporosis often leads to fragility fractures of the hip, resulting in impaired quality of life and increased mortality. Augmenting the proximal femur could be an attractive option for prevention of fracture or fixation device failure. We describe a tissue engineering based strategy to enhance long-term bone formation in the femoral neck of osteoporotic rats by locally delivering bioactive molecules; recombinant human bone morphogenic protein-2 (rhBMP-2), and zoledronic acid (ZA) by using a calcium sulfate/ hydroxyapatite (CaS/HA) biomaterial. A defect was created by reaming the femoral neck canal of osteoporotic (OVX) rats and they were treated as follows: G1. Empty, G2. CaS/HA, G3. CaS/HA+Systemic ZA, G4. CaS/HA+Local ZA, and G5. CaS/HA+Local ZA+rhBMP-2. Bone formation was evaluated 6 months after treatment. Further, radioactively labeled 14C-ZA was used to study the bioavailability of ZA at the defect location, which was determined by using scintillation counting. Micro-CT indicated significantly higher bone volume in groups G4 and G5 compared with the other treatment groups. This was confirmed qualitatively by histological assessment. Addition of rhBMP-2 gave no additional benefit in this model. Local delivery of ZA performed better than systemic administration of ZA. Mechanical testing showed no differences between the groups, likely reflecting that the addition of bioactive molecules had limited effect on cortical bone or the choice of mechanical testing setup was not optimal. Scintillation counting revealed higher amounts of 14C-ZA present in the treated leg of G4 compared with its contralateral control and compared with G3, indicating that local ZA delivery can be used to achieve high local concentrations without causing a systemic effect. This long-term study shows that local delivery of ZA using a CaS/HA carrier can regenerate cancellous bone in the femoral neck canal and has clear implications for enhancing implant integration and fixation in fragile bone.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Femoral neck canal, Local delivery, Osteoporosis, Regenerative medicine, Zoledronic acid
in
Tissue Engineering - Part A
volume
26
issue
19-20
pages
10 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • pmid:32242474
  • scopus:85094220613
ISSN
1937-3341
DOI
10.1089/ten.tea.2020.0018
language
English
LU publication?
yes
id
23497cf7-1f95-4a4c-bab0-73ed0dd0ec9a
date added to LUP
2020-11-09 10:09:25
date last changed
2024-11-01 14:20:30
@article{23497cf7-1f95-4a4c-bab0-73ed0dd0ec9a,
  abstract     = {{<p>Osteoporosis often leads to fragility fractures of the hip, resulting in impaired quality of life and increased mortality. Augmenting the proximal femur could be an attractive option for prevention of fracture or fixation device failure. We describe a tissue engineering based strategy to enhance long-term bone formation in the femoral neck of osteoporotic rats by locally delivering bioactive molecules; recombinant human bone morphogenic protein-2 (rhBMP-2), and zoledronic acid (ZA) by using a calcium sulfate/ hydroxyapatite (CaS/HA) biomaterial. A defect was created by reaming the femoral neck canal of osteoporotic (OVX) rats and they were treated as follows: G1. Empty, G2. CaS/HA, G3. CaS/HA+Systemic ZA, G4. CaS/HA+Local ZA, and G5. CaS/HA+Local ZA+rhBMP-2. Bone formation was evaluated 6 months after treatment. Further, radioactively labeled <sup>14</sup>C-ZA was used to study the bioavailability of ZA at the defect location, which was determined by using scintillation counting. Micro-CT indicated significantly higher bone volume in groups G4 and G5 compared with the other treatment groups. This was confirmed qualitatively by histological assessment. Addition of rhBMP-2 gave no additional benefit in this model. Local delivery of ZA performed better than systemic administration of ZA. Mechanical testing showed no differences between the groups, likely reflecting that the addition of bioactive molecules had limited effect on cortical bone or the choice of mechanical testing setup was not optimal. Scintillation counting revealed higher amounts of <sup>14</sup>C-ZA present in the treated leg of G4 compared with its contralateral control and compared with G3, indicating that local ZA delivery can be used to achieve high local concentrations without causing a systemic effect. This long-term study shows that local delivery of ZA using a CaS/HA carrier can regenerate cancellous bone in the femoral neck canal and has clear implications for enhancing implant integration and fixation in fragile bone.</p>}},
  author       = {{Raina, Deepak Bushan and Širka, Aurimas and Qayoom, Irfan and Teotia, Arun Kumar and Liu, Yang and Tarasevicius, Sarunas and Tanner, Kathleen Elizabeth and Isaksson, Hanna and Kumar, Ashok and Tägil, Magnus and Lidgren, Lars}},
  issn         = {{1937-3341}},
  keywords     = {{Femoral neck canal; Local delivery; Osteoporosis; Regenerative medicine; Zoledronic acid}},
  language     = {{eng}},
  number       = {{19-20}},
  pages        = {{1042--1051}},
  publisher    = {{Mary Ann Liebert, Inc.}},
  series       = {{Tissue Engineering - Part A}},
  title        = {{Long-term response to a bioactive biphasic biomaterial in the femoral neck of osteoporotic rats}},
  url          = {{http://dx.doi.org/10.1089/ten.tea.2020.0018}},
  doi          = {{10.1089/ten.tea.2020.0018}},
  volume       = {{26}},
  year         = {{2020}},
}