Dual Growth Factor-modified Microspheres Nesting Human-derived Umbilical Cord Mesenchymal Stem Cells for Bone Regeneration

Overview

Journal J Biol Eng

Publisher Biomed Central

Specialty Biomedical Engineering

Date 2023 Jul 10

PMID 37430290

Authors

Wenzhi Song

Lanlan Zhao

Yuqi Gao

Chunyu Han

Shengrui Gao

Min Guo

Jianfei Bai

Liqiang Wang

Wanzhong Yin

Feng Wu

Peibiao Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Modular tissue engineering (MTE) is a novel "bottom-up" approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled into engineered biological tissues with repetitive functional microunits and form cellular networks. This is emerging as a promising strategy for reconstruction of biological tissue.

Results: Herein, we constructed a micromodule for MTE and developed engineered osteon-like microunits by inoculating human-derived umbilical cord mesenchymal stem cells (HUMSCs) onto nHA/PLGA microspheres with surface modification of dual growth factors (BMP2/bFGF). By evaluating the results of proliferation and osteogenic differentiation ability of HUMSCs in vitro, the optimal ratio of the dual growth factor (BMP2/bFGF) combination was derived as 5:5. In vivo assessments showed the great importance of HUMSCs for osteogneic differentiation. Ultimately, direct promotion of early osteo-differentiation manifested as upregulation of Runx-2 gene expression. The vascularization capability was evaluated by tube formation assays, demonstrating the importance of HUMSCs in the microunits for angiogenesis.

Conclusions: The modification of growth factors and HUMSCs showed ideal biocompatibility and osteogenesis combined with nHA/PLGA scaffolds. The micromodules constructed in the current study provide an efficient stem cell therapy strategy for bone defect repair.

Citing Articles

Stimulated Human Umbilical Cord Mesenchymal Stem Cells Enhance the Osteogenesis and Cranial Bone Regeneration through IL-32 Mediated P38 Signaling Pathway.

Zhang X, Zheng Y, Wang G, Liu Y, Wang Y, Jiang X Stem Cells Int. 2024; 2024:6693292.

PMID: 38510207 PMC: 10954361. DOI: 10.1155/2024/6693292.

Three Birds, One Stone: An Osteo-Microenvironment Stage-Regulative Scaffold for Bone Defect Repair through Modulating Early Osteo-Immunomodulation, Middle Neovascularization, and Later Osteogenesis.

Yuan Y, Xu Y, Mao Y, Liu H, Ou M, Lin Z Adv Sci (Weinh). 2023; 11(6):e2306428.

PMID: 38060833 PMC: 10853759. DOI: 10.1002/advs.202306428.

References

Vonau R, Bostrom M, Aspenberg P, Sams A . Combination of growth factors inhibits bone ingrowth in the bone harvest chamber. Clin Orthop Relat Res. 2001; (386):243-51. DOI: 10.1097/00003086-200105000-00032. View

Lee H, Rho J, Messersmith P . Facile Conjugation of Biomolecules onto Surfaces via Mussel Adhesive Protein Inspired Coatings. Adv Mater. 2009; 21(4):431-434. PMC: 2755254. DOI: 10.1002/adma.200801222. View

Lee J, Lee K, Moon S, Chung H, Lee J, Um S . Mussel-inspired cell-adhesion peptide modification for enhanced endothelialization of decellularized blood vessels. Macromol Biosci. 2014; 14(8):1181-9. DOI: 10.1002/mabi.201400052. View

Liu Y, Lin Z, Guo J, Xu G, Li Y, Xu T . Notoginsenoside R1 significantly promotes in vitro osteoblastogenesis. Int J Mol Med. 2016; 38(2):537-44. DOI: 10.3892/ijmm.2016.2652. View

Simmons C, Alsberg E, Hsiong S, Kim W, Mooney D . Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. Bone. 2004; 35(2):562-9. DOI: 10.1016/j.bone.2004.02.027. View

Szewczyk P, Metwally S, Krysiak Z, Kaniuk L, Karbowniczek J, Stachewicz U . Enhanced osteoblasts adhesion and collagen formation on biomimetic polyvinylidene fluoride (PVDF) films for bone regeneration. Biomed Mater. 2019; 14(6):065006. DOI: 10.1088/1748-605X/ab3c20. View

Zhang N, Gao T, Wang Y, Wang Z, Zhang P, Liu J . Environmental pH-controlled loading and release of protein on mesoporous hydroxyapatite nanoparticles for bone tissue engineering. Mater Sci Eng C Mater Biol Appl. 2014; 46:158-65. DOI: 10.1016/j.msec.2014.10.014. View

Fortino V, Chen R, Pelaez D, Cheung H . Neurogenesis of neural crest-derived periodontal ligament stem cells by EGF and bFGF. J Cell Physiol. 2013; 229(4):479-88. PMC: 4292882. DOI: 10.1002/jcp.24468. View

Akita S, Fukui M, Nakagawa H, Fujii T, Akino K . Cranial bone defect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast growth factor. Wound Repair Regen. 2004; 12(2):252-9. DOI: 10.1111/j.1067-1927.2004.012118.x. View

10.

Sun P, Shi A, Shen C, Liu Y, Wu G, Feng J . Human salivary histatin-1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)-induced osteogenesis and angiogenesis. FEBS Open Bio. 2020; 10(8):1503-1515. PMC: 7396425. DOI: 10.1002/2211-5463.12906. View

11.

Alam S, Ueki K, Marukawa K, Ohara T, Hase T, Takazakura D . Expression of bone morphogenetic protein 2 and fibroblast growth factor 2 during bone regeneration using different implant materials as an onlay bone graft in rabbit mandibles. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 103(1):16-26. DOI: 10.1016/j.tripleo.2006.01.019. View

12.

Wu J, Huang G, He W, Wang P, Tong Z, Jia Q . Basic fibroblast growth factor enhances stemness of human stem cells from the apical papilla. J Endod. 2012; 38(5):614-22. PMC: 3499972. DOI: 10.1016/j.joen.2012.01.014. View

13.

Lertkiatmongkol P, Liao D, Mei H, Hu Y, Newman P . Endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31). Curr Opin Hematol. 2016; 23(3):253-9. PMC: 4986701. DOI: 10.1097/MOH.0000000000000239. View

14.

Fang J, Zhang Y, Yan S, Liu Z, He S, Cui L . Poly(L-glutamic acid)/chitosan polyelectrolyte complex porous microspheres as cell microcarriers for cartilage regeneration. Acta Biomater. 2013; 10(1):276-88. DOI: 10.1016/j.actbio.2013.09.002. View

15.

Samorezov J, Headley E, Everett C, Alsberg E . Sustained presentation of BMP-2 enhances osteogenic differentiation of human adipose-derived stem cells in gelatin hydrogels. J Biomed Mater Res A. 2016; 104(6):1387-97. PMC: 6930142. DOI: 10.1002/jbm.a.35668. View

16.

Cho H, Perikamana S, Lee J, Lee J, Lee K, Shin C . Effective immobilization of BMP-2 mediated by polydopamine coating on biodegradable nanofibers for enhanced in vivo bone formation. ACS Appl Mater Interfaces. 2014; 6(14):11225-35. DOI: 10.1021/am501391z. View

17.

Priyam A, Nagar P, Kumar Sharma A, Kumar P . Mussel-inspired polydopamine-polyethylenimine conjugated nanoparticles as efficient gene delivery vectors for mammalian cells. Colloids Surf B Biointerfaces. 2017; 161:403-412. DOI: 10.1016/j.colsurfb.2017.10.063. View

18.

Schmidmaier G, Wildemann B, Gabelein T, Heeger J, Kandziora F, Haas N . Synergistic effect of IGF-I and TGF-beta1 on fracture healing in rats: single versus combined application of IGF-I and TGF-beta1. Acta Orthop Scand. 2003; 74(5):604-10. DOI: 10.1080/00016470310018036 . View

19.

Kim S, Song S, Yun Y, Choi B, Kwon I, Bae M . The effect of immobilization of heparin and bone morphogenic protein-2 (BMP-2) to titanium surfaces on inflammation and osteoblast function. Biomaterials. 2010; 32(2):366-73. DOI: 10.1016/j.biomaterials.2010.09.008. View

20.

Gao T, Zhang N, Wang Z, Wang Y, Liu Y, Ito Y . Biodegradable Microcarriers of Poly(Lactide-co-Glycolide) and Nano-Hydroxyapatite Decorated with IGF-1 via Polydopamine Coating for Enhancing Cell Proliferation and Osteogenic Differentiation. Macromol Biosci. 2015; 15(8):1070-80. DOI: 10.1002/mabi.201500069. View