Dual Delivery of BMP2 and IGF1 Through Injectable Hydrogel Promotes Cranial Bone Defect Healing

Young Bum Park; Sien Lin; Yan Bai; Seyedsina Moeinzadeh; Sungwoo Kim; Jianping Huang; Uilyong Lee; Ngan Fong Huang; Yunzhi Peter Yang

doi:10.1089/ten.tea.2022.0002

Dual Delivery of BMP2 and IGF1 Through Injectable Hydrogel Promotes Cranial Bone Defect Healing

Young Bum Park, Sien Lin, Yan Bai, Seyedsina Moeinzadeh, Sungwoo Kim, Jianping Huang, Uilyong Lee, Ngan Fong Huang, Yunzhi Peter Yang

Department of Prosthodontics

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

9 Citations (Scopus)

Abstract

Critical-sized cranial bone defect remains a great clinical challenge. With advantages in regenerative medicine, injectable hydrogels incorporated with bioactive molecules show great potential in promoting cranial bone repair. Recently, we developed a dual delivery system by sequential release of bone morphogenetic protein 2 (BMP2) followed by insulin-like growth factor 1 (IGF1) in microparticles (MPs), and an injectable alginate/collagen (alg/col)-based hydrogel. In this study, we aim to evaluate the effect of dual delivery of BMP2 and IGF1 in MPs through the injectable hydrogel in critical-sized cranial bone defect healing. The gelatin MPs loaded with BMP2 and poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH) MPs loaded with IGF1 were prepared, respectively. The encapsulation efficiency and release profile of growth factors in MPs were measured. A cranial defect model was applied to evaluate the efficacy of the dual delivery system in bone regeneration. Adult Sprague Dawley rats were subjected to osteotomy to make an ∅8-mm cranial defect. The injectable hydrogel containing MPs loaded with BMP2 (2 μg), IGF1 (2 μg), or a combination of BMP2 (1 μg) and IGF1 (1 μg) were injected to the defect site. New bone formation was evaluated by microcomputed tomography, histological analysis, and immunohistochemistry after 4 or 8 weeks. Data showed that dual delivery of the low-dose BMP2 and IGF1 in MPs through alg/col-based hydrogel successfully restored cranial bone as early as 4 weeks after implantation, whose effect was comparable to the single delivery of high-dose BMP2 in MPs. In conclusion, this study suggests that dual delivery of BMP2 and IGF1 in MPs in alg/col-based hydrogel achieves early bone regeneration in critical-sized bone defect, with advantage in reducing the dose of BMP2.

Original language	English
Pages (from-to)	760-769
Number of pages	10
Journal	Tissue Engineering - Part A
Volume	28
Issue number	17-18
DOIs	https://doi.org/10.1089/ten.tea.2022.0002
Publication status	Published - 2022 Sept 1

Bibliographical note

Funding Information:
National Institutes of Health grant U01AR069395 to Y.P.Y., R01AR072613 to Y.P.Y., R01AR074458 to Y.P.Y., and NIH1S10OD02349701 to Timothy C. Doyle. Department of Defense grant W81XWH-20-1-0343 to Y.P.Y. Yonsei University School of Dentistry Intramural Faculty Research Grant 6-2020-0029 to Y.P., and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education NRF-2020R 1F 1A 104997812: 2021-31-0016 to Y.P.

Funding Information:
National Institutes of Health grant U01AR069395 to Y.P.Y., R01AR072613 to Y.P.Y., R01AR074458 to Y.P.Y., and NIH1S10OD02349701 to Timothy C. Doyle. Department of Defense grant W81XWH-20-1-0343 to Y.P.Y. Yonsei University School of Dentistry Intramural Faculty Research Grant 6-2020-0029 to Y.P., and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education NRF-2020R 1F 1A 104997812: 2021-31-0016 to Y.P.

Publisher Copyright:
Copyright © 2022, Mary Ann Liebert, Inc.

All Science Journal Classification (ASJC) codes

Bioengineering
Biochemistry
Biomedical Engineering
Biomaterials

Access to Document

10.1089/ten.tea.2022.0002

Cite this

@article{707f74c562a64228a1f72a0a26fb394e,

title = "Dual Delivery of BMP2 and IGF1 Through Injectable Hydrogel Promotes Cranial Bone Defect Healing",

abstract = "Critical-sized cranial bone defect remains a great clinical challenge. With advantages in regenerative medicine, injectable hydrogels incorporated with bioactive molecules show great potential in promoting cranial bone repair. Recently, we developed a dual delivery system by sequential release of bone morphogenetic protein 2 (BMP2) followed by insulin-like growth factor 1 (IGF1) in microparticles (MPs), and an injectable alginate/collagen (alg/col)-based hydrogel. In this study, we aim to evaluate the effect of dual delivery of BMP2 and IGF1 in MPs through the injectable hydrogel in critical-sized cranial bone defect healing. The gelatin MPs loaded with BMP2 and poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH) MPs loaded with IGF1 were prepared, respectively. The encapsulation efficiency and release profile of growth factors in MPs were measured. A cranial defect model was applied to evaluate the efficacy of the dual delivery system in bone regeneration. Adult Sprague Dawley rats were subjected to osteotomy to make an ∅8-mm cranial defect. The injectable hydrogel containing MPs loaded with BMP2 (2 μg), IGF1 (2 μg), or a combination of BMP2 (1 μg) and IGF1 (1 μg) were injected to the defect site. New bone formation was evaluated by microcomputed tomography, histological analysis, and immunohistochemistry after 4 or 8 weeks. Data showed that dual delivery of the low-dose BMP2 and IGF1 in MPs through alg/col-based hydrogel successfully restored cranial bone as early as 4 weeks after implantation, whose effect was comparable to the single delivery of high-dose BMP2 in MPs. In conclusion, this study suggests that dual delivery of BMP2 and IGF1 in MPs in alg/col-based hydrogel achieves early bone regeneration in critical-sized bone defect, with advantage in reducing the dose of BMP2.",

author = "Park, {Young Bum} and Sien Lin and Yan Bai and Seyedsina Moeinzadeh and Sungwoo Kim and Jianping Huang and Uilyong Lee and Huang, {Ngan Fong} and Yang, {Yunzhi Peter}",

note = "Funding Information: National Institutes of Health grant U01AR069395 to Y.P.Y., R01AR072613 to Y.P.Y., R01AR074458 to Y.P.Y., and NIH1S10OD02349701 to Timothy C. Doyle. Department of Defense grant W81XWH-20-1-0343 to Y.P.Y. Yonsei University School of Dentistry Intramural Faculty Research Grant 6-2020-0029 to Y.P., and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education NRF-2020R 1F 1A 104997812: 2021-31-0016 to Y.P. Funding Information: National Institutes of Health grant U01AR069395 to Y.P.Y., R01AR072613 to Y.P.Y., R01AR074458 to Y.P.Y., and NIH1S10OD02349701 to Timothy C. Doyle. Department of Defense grant W81XWH-20-1-0343 to Y.P.Y. Yonsei University School of Dentistry Intramural Faculty Research Grant 6-2020-0029 to Y.P., and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education NRF-2020R 1F 1A 104997812: 2021-31-0016 to Y.P. Publisher Copyright: Copyright {\textcopyright} 2022, Mary Ann Liebert, Inc.",

year = "2022",

month = sep,

day = "1",

doi = "10.1089/ten.tea.2022.0002",

language = "English",

volume = "28",

pages = "760--769",

journal = "Tissue Engineering - Part A",

issn = "1937-3341",

publisher = "Mary Ann Liebert Inc.",

number = "17-18",

}

TY - JOUR

T1 - Dual Delivery of BMP2 and IGF1 Through Injectable Hydrogel Promotes Cranial Bone Defect Healing

AU - Park, Young Bum

AU - Lin, Sien

AU - Bai, Yan

AU - Moeinzadeh, Seyedsina

AU - Kim, Sungwoo

AU - Huang, Jianping

AU - Lee, Uilyong

AU - Huang, Ngan Fong

AU - Yang, Yunzhi Peter

N1 - Funding Information: National Institutes of Health grant U01AR069395 to Y.P.Y., R01AR072613 to Y.P.Y., R01AR074458 to Y.P.Y., and NIH1S10OD02349701 to Timothy C. Doyle. Department of Defense grant W81XWH-20-1-0343 to Y.P.Y. Yonsei University School of Dentistry Intramural Faculty Research Grant 6-2020-0029 to Y.P., and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education NRF-2020R 1F 1A 104997812: 2021-31-0016 to Y.P. Funding Information: National Institutes of Health grant U01AR069395 to Y.P.Y., R01AR072613 to Y.P.Y., R01AR074458 to Y.P.Y., and NIH1S10OD02349701 to Timothy C. Doyle. Department of Defense grant W81XWH-20-1-0343 to Y.P.Y. Yonsei University School of Dentistry Intramural Faculty Research Grant 6-2020-0029 to Y.P., and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education NRF-2020R 1F 1A 104997812: 2021-31-0016 to Y.P. Publisher Copyright: Copyright © 2022, Mary Ann Liebert, Inc.

PY - 2022/9/1

Y1 - 2022/9/1

N2 - Critical-sized cranial bone defect remains a great clinical challenge. With advantages in regenerative medicine, injectable hydrogels incorporated with bioactive molecules show great potential in promoting cranial bone repair. Recently, we developed a dual delivery system by sequential release of bone morphogenetic protein 2 (BMP2) followed by insulin-like growth factor 1 (IGF1) in microparticles (MPs), and an injectable alginate/collagen (alg/col)-based hydrogel. In this study, we aim to evaluate the effect of dual delivery of BMP2 and IGF1 in MPs through the injectable hydrogel in critical-sized cranial bone defect healing. The gelatin MPs loaded with BMP2 and poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH) MPs loaded with IGF1 were prepared, respectively. The encapsulation efficiency and release profile of growth factors in MPs were measured. A cranial defect model was applied to evaluate the efficacy of the dual delivery system in bone regeneration. Adult Sprague Dawley rats were subjected to osteotomy to make an ∅8-mm cranial defect. The injectable hydrogel containing MPs loaded with BMP2 (2 μg), IGF1 (2 μg), or a combination of BMP2 (1 μg) and IGF1 (1 μg) were injected to the defect site. New bone formation was evaluated by microcomputed tomography, histological analysis, and immunohistochemistry after 4 or 8 weeks. Data showed that dual delivery of the low-dose BMP2 and IGF1 in MPs through alg/col-based hydrogel successfully restored cranial bone as early as 4 weeks after implantation, whose effect was comparable to the single delivery of high-dose BMP2 in MPs. In conclusion, this study suggests that dual delivery of BMP2 and IGF1 in MPs in alg/col-based hydrogel achieves early bone regeneration in critical-sized bone defect, with advantage in reducing the dose of BMP2.

AB - Critical-sized cranial bone defect remains a great clinical challenge. With advantages in regenerative medicine, injectable hydrogels incorporated with bioactive molecules show great potential in promoting cranial bone repair. Recently, we developed a dual delivery system by sequential release of bone morphogenetic protein 2 (BMP2) followed by insulin-like growth factor 1 (IGF1) in microparticles (MPs), and an injectable alginate/collagen (alg/col)-based hydrogel. In this study, we aim to evaluate the effect of dual delivery of BMP2 and IGF1 in MPs through the injectable hydrogel in critical-sized cranial bone defect healing. The gelatin MPs loaded with BMP2 and poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH) MPs loaded with IGF1 were prepared, respectively. The encapsulation efficiency and release profile of growth factors in MPs were measured. A cranial defect model was applied to evaluate the efficacy of the dual delivery system in bone regeneration. Adult Sprague Dawley rats were subjected to osteotomy to make an ∅8-mm cranial defect. The injectable hydrogel containing MPs loaded with BMP2 (2 μg), IGF1 (2 μg), or a combination of BMP2 (1 μg) and IGF1 (1 μg) were injected to the defect site. New bone formation was evaluated by microcomputed tomography, histological analysis, and immunohistochemistry after 4 or 8 weeks. Data showed that dual delivery of the low-dose BMP2 and IGF1 in MPs through alg/col-based hydrogel successfully restored cranial bone as early as 4 weeks after implantation, whose effect was comparable to the single delivery of high-dose BMP2 in MPs. In conclusion, this study suggests that dual delivery of BMP2 and IGF1 in MPs in alg/col-based hydrogel achieves early bone regeneration in critical-sized bone defect, with advantage in reducing the dose of BMP2.

UR - http://www.scopus.com/inward/record.url?scp=85133289764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85133289764&partnerID=8YFLogxK

U2 - 10.1089/ten.tea.2022.0002

DO - 10.1089/ten.tea.2022.0002

M3 - Article

C2 - 35357948

AN - SCOPUS:85133289764

SN - 1937-3341

VL - 28

SP - 760

EP - 769

JO - Tissue Engineering - Part A

JF - Tissue Engineering - Part A

IS - 17-18

ER -

Dual Delivery of BMP2 and IGF1 Through Injectable Hydrogel Promotes Cranial Bone Defect Healing

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this