Synthesis and Characterization of a Biocomposite Bone Bandage for Controlled Delivery of Bone-Active Drugs in Fracture Nonunions
Raina, Deepak Bushan LU ; Glencross, Alexandra ; Chaher, Nadia ; Liu, Yang LU ; Lidgren, Lars LU ; Isaksson, Hanna LU
and Tägil, Magnus
LU
(2020)
In ACS Biomaterials Science and Engineering
6(5).
p.2867-2878
- Abstract
Fracture nonunions are common in orthopedics and their treatment often involves multiple surgical interventions. The aim of this study was to fabricate and characterize a gelatin-nano-hydroxyapatite membrane (GM)-based bone bandage for controlled delivery of bio-active molecules; recombinant human bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) to promote osteoinduction and prevent callus resorption, respectively. In vitro cell-material interaction experiments using MC3T3 cells seeded on the GM indicated good biocompatibility. rhBMP-2-functionalized GM promoted osteogenic differentiation of MC3T3 cells and the rhBMP-2 bio-activity thus remained, as indicated by increased levels of alkaline phosphatase compared to only GM.... (More)
Fracture nonunions are common in orthopedics and their treatment often involves multiple surgical interventions. The aim of this study was to fabricate and characterize a gelatin-nano-hydroxyapatite membrane (GM)-based bone bandage for controlled delivery of bio-active molecules; recombinant human bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) to promote osteoinduction and prevent callus resorption, respectively. In vitro cell-material interaction experiments using MC3T3 cells seeded on the GM indicated good biocompatibility. rhBMP-2-functionalized GM promoted osteogenic differentiation of MC3T3 cells and the rhBMP-2 bio-activity thus remained, as indicated by increased levels of alkaline phosphatase compared to only GM. The GM released a small amount (1.1%) of rhBMP-2 in vitro over a period of 5 weeks, demonstrating a strong interaction of rhBMP-2 with the GM. In the first animal study, the GM specimens loaded with rhBMP-2 or with the combination of rhBMP-2 + ZA were placed in the abdominal muscle pouch of rats. In the GM + rhBMP-2 + ZA group, significantly higher bone volume (21.5 ± 5.9 vs 2.7 ± 1.0 mm3) and area (3.3 ± 2.3 vs 1.0 ± 0.4 mm2) of bone were observed compared to GM + rhBMP-2 after 4 weeks, as indicated by micro-computed tomography and histomorphometry, respectively. Finally, a nonunion model in rats was used to evaluate the efficacy of the GM bandage and bio-active molecules in healing of fracture nonunions. The GM functionalized with rhBMP-2 + ZA led to higher bone formation around the fracture (63.9 ± 19.0 vs 31.8 ± 3.7 mm3) and stronger fracture callus (110.8 ± 46.8 vs 45.6 ± 17.8 N) compared to the empty controls. However, the overall union rate was only marginally improved. The GM alone or combined with ZA did not aid in bone healing in this model. Thus, this study shows that controlled delivery of rhBMP-2 + ZA via the developed GM is a promising approach that could aid in earlier full load bearing in patients with nonunion.
(Less)
- author
- Raina, Deepak Bushan
LU
; Glencross, Alexandra
; Chaher, Nadia
; Liu, Yang
LU
; Lidgren, Lars
LU
; Isaksson, Hanna
LU
and Tägil, Magnus
LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- gelatin, nano-hydroxyapatite, nonunion, rhBMP-2, zoledronic acid
- in
- ACS Biomaterials Science and Engineering
- volume
- 6
- issue
- 5
- pages
- 12 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:33463281
- scopus:85097952625
- ISSN
- 2373-9878
- DOI
- 10.1021/acsbiomaterials.9b01574
- language
- English
- LU publication?
- yes
- id
- b6970b89-e334-41a5-9696-f5f6773d3b4b
- date added to LUP
- 2021-01-08 09:58:52
- date last changed
- 2024-03-20 23:13:02
@article{b6970b89-e334-41a5-9696-f5f6773d3b4b,
abstract = {{<p>Fracture nonunions are common in orthopedics and their treatment often involves multiple surgical interventions. The aim of this study was to fabricate and characterize a gelatin-nano-hydroxyapatite membrane (GM)-based bone bandage for controlled delivery of bio-active molecules; recombinant human bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) to promote osteoinduction and prevent callus resorption, respectively. In vitro cell-material interaction experiments using MC3T3 cells seeded on the GM indicated good biocompatibility. rhBMP-2-functionalized GM promoted osteogenic differentiation of MC3T3 cells and the rhBMP-2 bio-activity thus remained, as indicated by increased levels of alkaline phosphatase compared to only GM. The GM released a small amount (1.1%) of rhBMP-2 in vitro over a period of 5 weeks, demonstrating a strong interaction of rhBMP-2 with the GM. In the first animal study, the GM specimens loaded with rhBMP-2 or with the combination of rhBMP-2 + ZA were placed in the abdominal muscle pouch of rats. In the GM + rhBMP-2 + ZA group, significantly higher bone volume (21.5 ± 5.9 vs 2.7 ± 1.0 mm3) and area (3.3 ± 2.3 vs 1.0 ± 0.4 mm2) of bone were observed compared to GM + rhBMP-2 after 4 weeks, as indicated by micro-computed tomography and histomorphometry, respectively. Finally, a nonunion model in rats was used to evaluate the efficacy of the GM bandage and bio-active molecules in healing of fracture nonunions. The GM functionalized with rhBMP-2 + ZA led to higher bone formation around the fracture (63.9 ± 19.0 vs 31.8 ± 3.7 mm3) and stronger fracture callus (110.8 ± 46.8 vs 45.6 ± 17.8 N) compared to the empty controls. However, the overall union rate was only marginally improved. The GM alone or combined with ZA did not aid in bone healing in this model. Thus, this study shows that controlled delivery of rhBMP-2 + ZA via the developed GM is a promising approach that could aid in earlier full load bearing in patients with nonunion. </p>}},
author = {{Raina, Deepak Bushan and Glencross, Alexandra and Chaher, Nadia and Liu, Yang and Lidgren, Lars and Isaksson, Hanna and Tägil, Magnus}},
issn = {{2373-9878}},
keywords = {{gelatin; nano-hydroxyapatite; nonunion; rhBMP-2; zoledronic acid}},
language = {{eng}},
number = {{5}},
pages = {{2867--2878}},
publisher = {{The American Chemical Society (ACS)}},
series = {{ACS Biomaterials Science and Engineering}},
title = {{Synthesis and Characterization of a Biocomposite Bone Bandage for Controlled Delivery of Bone-Active Drugs in Fracture Nonunions}},
url = {{http://dx.doi.org/10.1021/acsbiomaterials.9b01574}},
doi = {{10.1021/acsbiomaterials.9b01574}},
volume = {{6}},
year = {{2020}},
}