Development of osteopromotive poly (octamethylene citrate glycerophosphate) for enhanced bone regeneration

Yun He, Qiyao Li, Chuying Ma, Denghui Xie, Limei Li, Yitao Zhao, Dingying Shan, Sarah K. Chomos, Cheng Dong, John W. Tierney, Lin Sun, Di Lu, Li Gui, Jian Yang

Research output: Contribution to journalArticle

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Abstract

The design and development of bioactive materials that are inherently conducive for osteointegration and bone regeneration with tunable mechanical properties and degradation remains a challenge. Herein, we report the development of a new class of citrate-based materials with glycerophosphate salts, β-glycerophosphate disodium (β-GP-Na) and glycerophosphate calcium (GP-Ca), incorporated through a simple and convenient one-pot condensation reaction, which might address the above challenge in the search of suitable orthopedic biomaterials. Tensile strength of the resultant poly (octamethylene citrate glycerophosphate), POC-βGP-Na and POC-GP-Ca, was as high as 28.2 ± 2.44 MPa and 22.76 ± 1.06 MPa, respectively. The initial modulus ranged from 5.28 ± 0.56 MPa to 256.44 ± 22.88 MPa. The mechanical properties and degradation rate of POC-GP could be controlled by varying the type of salts, and the feeding ratio of salts introduced. Particularly, POC-GP-Ca demonstrated better cytocompatibility and the corresponding composite POC-GP-Ca/hydroxyapatite (HA) also elicited improved osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro, as compared to POC-βGP-Na/HA and POC/HA. The superior in-vivo performance of POC-GP-Ca/HA microparticle scaffolds in promoting bone regeneration over POC-βGP-Na/HA and POC/HA was further confirmed in a rabbit femoral condyle defect model. Taken together, the tunability of mechanical properties and degradation rates, together with the osteopromotive nature of POC-GP polymers make these materials, especially POC-GP-Ca well suited for bone tissue engineering applications. Statement of Significance: The design and development of bioactive materials that are inherently conducive for osteointegration and bone regeneration with tunable mechanical properties and degradation remains a challenge. Herein, we report the development of a new class of citrate-based materials with glycerophosphate salts, β-glycerophosphate disodium (β-GPNa) and glycerophosphate calcium (GPCa), incorporated through a simple and convenient one-pot condensation reaction. The resultant POC-GP polymers showed significantly improved mechanical property and tunable degradation rate. Within the formulation investigated, POC-GPCa/HA composite further demonstrated better bioactivity in favoring osteogenic differentiation of hMSCs in vitro and promoted bone regeneration in rabbit femoral condyle defects. The development of POC-GP expands the repertoire of the well-recognized citrate-based biomaterials to meet the ever-increasing needs for functional biomaterials in tissue engineering and other biomedical applications.

Original languageEnglish (US)
Pages (from-to)180-191
Number of pages12
JournalActa Biomaterialia
Volume93
DOIs
StatePublished - Jul 15 2019

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Glycerophosphates
Bone Regeneration
Citric Acid
Durapatite
Hydroxyapatite
Calcium
Bone
Biocompatible Materials
Degradation
Mechanical properties
Salts
Biomaterials
Condensation reactions
Stem cells
Tissue engineering
Polymers
Tissue Engineering
Thigh
Mesenchymal Stromal Cells
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

He, Yun ; Li, Qiyao ; Ma, Chuying ; Xie, Denghui ; Li, Limei ; Zhao, Yitao ; Shan, Dingying ; Chomos, Sarah K. ; Dong, Cheng ; Tierney, John W. ; Sun, Lin ; Lu, Di ; Gui, Li ; Yang, Jian. / Development of osteopromotive poly (octamethylene citrate glycerophosphate) for enhanced bone regeneration. In: Acta Biomaterialia. 2019 ; Vol. 93. pp. 180-191.
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abstract = "The design and development of bioactive materials that are inherently conducive for osteointegration and bone regeneration with tunable mechanical properties and degradation remains a challenge. Herein, we report the development of a new class of citrate-based materials with glycerophosphate salts, β-glycerophosphate disodium (β-GP-Na) and glycerophosphate calcium (GP-Ca), incorporated through a simple and convenient one-pot condensation reaction, which might address the above challenge in the search of suitable orthopedic biomaterials. Tensile strength of the resultant poly (octamethylene citrate glycerophosphate), POC-βGP-Na and POC-GP-Ca, was as high as 28.2 ± 2.44 MPa and 22.76 ± 1.06 MPa, respectively. The initial modulus ranged from 5.28 ± 0.56 MPa to 256.44 ± 22.88 MPa. The mechanical properties and degradation rate of POC-GP could be controlled by varying the type of salts, and the feeding ratio of salts introduced. Particularly, POC-GP-Ca demonstrated better cytocompatibility and the corresponding composite POC-GP-Ca/hydroxyapatite (HA) also elicited improved osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro, as compared to POC-βGP-Na/HA and POC/HA. The superior in-vivo performance of POC-GP-Ca/HA microparticle scaffolds in promoting bone regeneration over POC-βGP-Na/HA and POC/HA was further confirmed in a rabbit femoral condyle defect model. Taken together, the tunability of mechanical properties and degradation rates, together with the osteopromotive nature of POC-GP polymers make these materials, especially POC-GP-Ca well suited for bone tissue engineering applications. Statement of Significance: The design and development of bioactive materials that are inherently conducive for osteointegration and bone regeneration with tunable mechanical properties and degradation remains a challenge. Herein, we report the development of a new class of citrate-based materials with glycerophosphate salts, β-glycerophosphate disodium (β-GPNa) and glycerophosphate calcium (GPCa), incorporated through a simple and convenient one-pot condensation reaction. The resultant POC-GP polymers showed significantly improved mechanical property and tunable degradation rate. Within the formulation investigated, POC-GPCa/HA composite further demonstrated better bioactivity in favoring osteogenic differentiation of hMSCs in vitro and promoted bone regeneration in rabbit femoral condyle defects. The development of POC-GP expands the repertoire of the well-recognized citrate-based biomaterials to meet the ever-increasing needs for functional biomaterials in tissue engineering and other biomedical applications.",
author = "Yun He and Qiyao Li and Chuying Ma and Denghui Xie and Limei Li and Yitao Zhao and Dingying Shan and Chomos, {Sarah K.} and Cheng Dong and Tierney, {John W.} and Lin Sun and Di Lu and Li Gui and Jian Yang",
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He, Y, Li, Q, Ma, C, Xie, D, Li, L, Zhao, Y, Shan, D, Chomos, SK, Dong, C, Tierney, JW, Sun, L, Lu, D, Gui, L & Yang, J 2019, 'Development of osteopromotive poly (octamethylene citrate glycerophosphate) for enhanced bone regeneration', Acta Biomaterialia, vol. 93, pp. 180-191. https://doi.org/10.1016/j.actbio.2019.03.050

Development of osteopromotive poly (octamethylene citrate glycerophosphate) for enhanced bone regeneration. / He, Yun; Li, Qiyao; Ma, Chuying; Xie, Denghui; Li, Limei; Zhao, Yitao; Shan, Dingying; Chomos, Sarah K.; Dong, Cheng; Tierney, John W.; Sun, Lin; Lu, Di; Gui, Li; Yang, Jian.

In: Acta Biomaterialia, Vol. 93, 15.07.2019, p. 180-191.

Research output: Contribution to journalArticle

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T1 - Development of osteopromotive poly (octamethylene citrate glycerophosphate) for enhanced bone regeneration

AU - He, Yun

AU - Li, Qiyao

AU - Ma, Chuying

AU - Xie, Denghui

AU - Li, Limei

AU - Zhao, Yitao

AU - Shan, Dingying

AU - Chomos, Sarah K.

AU - Dong, Cheng

AU - Tierney, John W.

AU - Sun, Lin

AU - Lu, Di

AU - Gui, Li

AU - Yang, Jian

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N2 - The design and development of bioactive materials that are inherently conducive for osteointegration and bone regeneration with tunable mechanical properties and degradation remains a challenge. Herein, we report the development of a new class of citrate-based materials with glycerophosphate salts, β-glycerophosphate disodium (β-GP-Na) and glycerophosphate calcium (GP-Ca), incorporated through a simple and convenient one-pot condensation reaction, which might address the above challenge in the search of suitable orthopedic biomaterials. Tensile strength of the resultant poly (octamethylene citrate glycerophosphate), POC-βGP-Na and POC-GP-Ca, was as high as 28.2 ± 2.44 MPa and 22.76 ± 1.06 MPa, respectively. The initial modulus ranged from 5.28 ± 0.56 MPa to 256.44 ± 22.88 MPa. The mechanical properties and degradation rate of POC-GP could be controlled by varying the type of salts, and the feeding ratio of salts introduced. Particularly, POC-GP-Ca demonstrated better cytocompatibility and the corresponding composite POC-GP-Ca/hydroxyapatite (HA) also elicited improved osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro, as compared to POC-βGP-Na/HA and POC/HA. The superior in-vivo performance of POC-GP-Ca/HA microparticle scaffolds in promoting bone regeneration over POC-βGP-Na/HA and POC/HA was further confirmed in a rabbit femoral condyle defect model. Taken together, the tunability of mechanical properties and degradation rates, together with the osteopromotive nature of POC-GP polymers make these materials, especially POC-GP-Ca well suited for bone tissue engineering applications. Statement of Significance: The design and development of bioactive materials that are inherently conducive for osteointegration and bone regeneration with tunable mechanical properties and degradation remains a challenge. Herein, we report the development of a new class of citrate-based materials with glycerophosphate salts, β-glycerophosphate disodium (β-GPNa) and glycerophosphate calcium (GPCa), incorporated through a simple and convenient one-pot condensation reaction. The resultant POC-GP polymers showed significantly improved mechanical property and tunable degradation rate. Within the formulation investigated, POC-GPCa/HA composite further demonstrated better bioactivity in favoring osteogenic differentiation of hMSCs in vitro and promoted bone regeneration in rabbit femoral condyle defects. The development of POC-GP expands the repertoire of the well-recognized citrate-based biomaterials to meet the ever-increasing needs for functional biomaterials in tissue engineering and other biomedical applications.

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