Novel artificial tricalcium phosphate and magnesium composite graft facilitates angiogenesis in bone healing

Yuan-Hsin Tsai; Chun-Chieh Tseng; Yun-Chan Lin; Howida M Nail; Kuan-Yu Chiu; Yen-Hao Chang; Ming-Wei Chang; Feng-Huei Lin; Hui-Min David Wang

doi:10.1016/j.bj.2024.100750

Novel artificial tricalcium phosphate and magnesium composite graft facilitates angiogenesis in bone healing

Yuan-Hsin Tsai
, Chun-Chieh Tseng
, Yun-Chan Lin
, Howida M Nail
, Kuan-Yu Chiu
, Yen-Hao Chang
, Ming-Wei Chang
, Feng-Huei Lin
, Hui-Min David Wang

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

40 Downloads (Pure)

Abstract

Background: Critical bone defects pose a significant challenge for orthopedic surgeons. Autologous bone grafting is the golden standard. However, it is hindered by issues such as donor site morbidity and limited availability. Commercially available artificial bone grafts may encounter challenges in properly integrating the surrounding bone tissue, potentially leading to delayed or incomplete healing. Furthermore, magnesium deficiency has been shown to negatively affect localized angiogenesis and bone repair. As a result, creating a synthetic biomaterial that includes magnesium could serve as an excellent bone substitute. The study aims to evaluate and test the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM). Methods: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. Results: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 min and a compressive strength of 4.39 ± 0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. Conclusion: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.

Original language	English
Article number	100750
Pages (from-to)	1-42
Number of pages	43
Journal	Biomedical journal
Volume	48
Issue number	2
Early online date	3 Jun 2024
DOIs	https://doi.org/10.1016/j.bj.2024.100750
Publication status	Published (in print/issue) - 30 Apr 2025

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Data Availability Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Funding

Yuan-Hsin Tsai carried out his thesis research under the auspices of the Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, and National Health Research Institutes. We thank Li-Heng Liu for his (or her?) helpful assistance and support. This research was supported by the Ministry of Science and Technology, Taiwan for the grants MOST 110-2221-E-005-010, MOST 111-2221-E-005-009, and MOST 111-2221-E-005 -026 -MY3. We also thank the grant supports from National Chung Hsing University (ENABLE: 108ST001B and 110ST001G), Kasesart University Joint Research Project (108RA129A), and NCHU-MIRDC Bilateral Joint Research Project (110S0703B). Yuan-Hsin Tsai carried out his thesis research under the auspices of the Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, and National Health Research Institutes. We thank Li-Heng Liu for their helpful assistance and support. This research was supported by the Ministry of Science and Technology, Taiwan for the grants (MOST 110-2221-E-005-010, MOST 111-2221-E-005-009, and MOST 111-2221-E-005 -026 -MY3). We also thank National Chung Hsing University (ENABLE: 108ST001B and 110ST001G), Kasesart University Joint Research Project (108RA129A), and NCHU-MIRDC Bilateral Joint Research Project (110S0703B).

Funders	Funder number
National Chung Hsing University
108RA129A
110ST001G, 110-2221-E-005-010, 111-2221-E-005 -026 -MY3, MOST 110-2221-E-005-010, MOST 111-2221-E-005-009, 108ST001B
110S0703B

Keywords

Magnesium
Tricalcium Phosphate
Bone graft
Critical bone defect
Tricalcium phosphate
Magnesium/chemistry
Biocompatible Materials/chemistry
Cell Differentiation/drug effects
Neovascularization, Physiologic/drug effects
Humans
Materials Testing
Bone Cements/chemistry
Calcium Phosphates/chemistry
Osteogenesis/drug effects
Angiogenesis
Animals
Bone Regeneration/drug effects
Bone Substitutes/chemistry
Bone Transplantation/methods
Bone and Bones/drug effects

Access to Document

10.1016/j.bj.2024.100750

1-s2.0-S2319417024000532-mainFinal published version, 62.3 KBLicence: CC BY-NC-ND

Cite this

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title = "Novel artificial tricalcium phosphate and magnesium composite graft facilitates angiogenesis in bone healing",

abstract = "Background: Critical bone defects pose a significant challenge for orthopedic surgeons. Autologous bone grafting is the golden standard. However, it is hindered by issues such as donor site morbidity and limited availability. Commercially available artificial bone grafts may encounter challenges in properly integrating the surrounding bone tissue, potentially leading to delayed or incomplete healing. Furthermore, magnesium deficiency has been shown to negatively affect localized angiogenesis and bone repair. As a result, creating a synthetic biomaterial that includes magnesium could serve as an excellent bone substitute. The study aims to evaluate and test the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM). Methods: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. Results: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 min and a compressive strength of 4.39 ± 0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. Conclusion: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.",

keywords = "Magnesium, Tricalcium Phosphate, Bone graft, Critical bone defect, Tricalcium phosphate, Magnesium/chemistry, Biocompatible Materials/chemistry, Cell Differentiation/drug effects, Neovascularization, Physiologic/drug effects, Humans, Materials Testing, Bone Cements/chemistry, Calcium Phosphates/chemistry, Osteogenesis/drug effects, Angiogenesis, Animals, Bone Regeneration/drug effects, Bone Substitutes/chemistry, Bone Transplantation/methods, Bone and Bones/drug effects",

author = "Yuan-Hsin Tsai and Chun-Chieh Tseng and Yun-Chan Lin and Nail, \{Howida M\} and Kuan-Yu Chiu and Yen-Hao Chang and Ming-Wei Chang and Feng-Huei Lin and Wang, \{Hui-Min David\}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

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month = apr,

day = "30",

doi = "10.1016/j.bj.2024.100750",

language = "English",

volume = "48",

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T1 - Novel artificial tricalcium phosphate and magnesium composite graft facilitates angiogenesis in bone healing

AU - Tsai, Yuan-Hsin

AU - Tseng, Chun-Chieh

AU - Lin, Yun-Chan

AU - Nail, Howida M

AU - Chiu, Kuan-Yu

AU - Chang, Yen-Hao

AU - Chang, Ming-Wei

AU - Lin, Feng-Huei

AU - Wang, Hui-Min David

PY - 2025/4/30

Y1 - 2025/4/30

N2 - Background: Critical bone defects pose a significant challenge for orthopedic surgeons. Autologous bone grafting is the golden standard. However, it is hindered by issues such as donor site morbidity and limited availability. Commercially available artificial bone grafts may encounter challenges in properly integrating the surrounding bone tissue, potentially leading to delayed or incomplete healing. Furthermore, magnesium deficiency has been shown to negatively affect localized angiogenesis and bone repair. As a result, creating a synthetic biomaterial that includes magnesium could serve as an excellent bone substitute. The study aims to evaluate and test the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM). Methods: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. Results: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 min and a compressive strength of 4.39 ± 0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. Conclusion: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.

AB - Background: Critical bone defects pose a significant challenge for orthopedic surgeons. Autologous bone grafting is the golden standard. However, it is hindered by issues such as donor site morbidity and limited availability. Commercially available artificial bone grafts may encounter challenges in properly integrating the surrounding bone tissue, potentially leading to delayed or incomplete healing. Furthermore, magnesium deficiency has been shown to negatively affect localized angiogenesis and bone repair. As a result, creating a synthetic biomaterial that includes magnesium could serve as an excellent bone substitute. The study aims to evaluate and test the morphological, mechanical, and biological properties of a calcium phosphate cement (CPC) sponge composed of tetracalcium phosphate (TTCP) and monocalcium phosphate monohydrate (MCPM). Methods: This study aims to develop biomedical materials composed mainly of TTCP and MCPM powder, magnesium powder, and collagen. The materials were prepared using a wet-stirred mill and freeze-dryer methods. The particle size, composition, and microstructure of the materials were investigated. Finally, the biological properties of these materials, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for biocompatibility, effects on bone cell differentiation by alkaline phosphatase (ALP) activity assay and tartrate-resistant acid phosphatase (TRAP) activity assay, and endothelial cell tube formation assay for angiogenesis, were evaluated as well. Results: The data showed that the sub-micron CPC powder, composed of TTCP/MCPM in a 3.5:1 ratio, had a setting time shorter than 15 min and a compressive strength of 4.39 ± 0.96 MPa. This reveals that the sub-micron CPC powder had an adequate setting time and mechanical strength. We found that the sub-micron CPC sponge containing magnesium had better biocompatibility, including increased proliferation and osteogenic induction effects without cytotoxicity. The CPC sponge containing magnesium also promoted angiogenesis. Conclusion: In summary, we introduced a novel CPC sponge, which had a similar property to human bone promoted the biological functions of bone cells, and could serve as a promising material used in bone regeneration for critical bone defects.

KW - Magnesium

KW - Tricalcium Phosphate

KW - Bone graft

KW - Critical bone defect

KW - Tricalcium phosphate

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KW - Biocompatible Materials/chemistry

KW - Cell Differentiation/drug effects

KW - Neovascularization, Physiologic/drug effects

KW - Humans

KW - Materials Testing

KW - Bone Cements/chemistry

KW - Calcium Phosphates/chemistry

KW - Osteogenesis/drug effects

KW - Angiogenesis

KW - Animals

KW - Bone Regeneration/drug effects

KW - Bone Substitutes/chemistry

KW - Bone Transplantation/methods

KW - Bone and Bones/drug effects

UR - https://www.scopus.com/pages/publications/105001569746

U2 - 10.1016/j.bj.2024.100750

DO - 10.1016/j.bj.2024.100750

M3 - Article

C2 - 38838984

SN - 2320-2890

VL - 48

SP - 1

EP - 42

JO - Biomedical journal

JF - Biomedical journal

IS - 2

M1 - 100750

ER -

Novel artificial tricalcium phosphate and magnesium composite graft facilitates angiogenesis in bone healing

Abstract

Bibliographical note

Data Availability Statement

Funding

Keywords

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