Bone Regeneration in Minipigs by Intrafibrillarly-mineralized Collagen Loaded with Autologous Periodontal Ligament Stem Cells

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 7

PMID 28874877

Citations 20

Authors

Ci Zhang

Boxi Yan

Zhen Cui

Shengjie Cui

Ting Zhang

Xuedong Wang

Dawei Liu

Ruli Yang

Nan Jiang

Yanheng Zhou

Yan Liu

Affiliations

Soon will be listed here.

Abstract

Biomimetic intrafibrillarly-mineralized collagen (IMC) is a promising scaffold for bone regeneration because of its structural and functional similarity to natural bone. The objective of this study was to evaluate the bone regeneration potential of IMC loaded with autologous periodontal ligament stem cells (PDLSCs) in large bone defects in minipigs. A macroporous IMC with a bone-like subfibrillar nanostructure was fabricated using a biomimetic bottom-up approach. Non-healing full thickness defects were established on the cranial bone in minipigs, and IMC and hydroxyapatite (HA) scaffolds seeded with autologous PDLSCs were implanted into these defects. Computed tomographic imaging, histology staining, and atomic force microscopy were applied to evaluate to the quantity, micro/nano structures, and mechanical performance of the neo-bone after 12 weeks of implantation. Compared with HA, IMC showed superior regeneration properties characterized by the profuse deposition of new bony structures with a normal architecture and vascularization. Immunohistochemistry showed that the runt-related transcription factor 2 and transcription factor Osterix were highly expressed in the neo-bone formed by IMC. Furthermore, the nanostructure and nanomechanics of the neo-bone formed by IMC were similar to that of natural bone. This study provides strong evidence for the future clinical applications of the IMC-based bone grafts.

Citing Articles

FAM96B negatively regulates FOSL1 to modulate the osteogenic differentiation and regeneration of periodontal ligament stem cells via ferroptosis.

Qin Q, Yang H, Guo R, Zheng Y, Huang Y, Jin L Stem Cell Res Ther. 2024; 15(1):471.

PMID: 39696611 PMC: 11656916. DOI: 10.1186/s13287-024-04083-7.

Advances in Bioceramics for Bone Regeneration: A Narrative Review.

Brochu B, Sturm S, Kawase De Queiroz Goncalves J, Mirsky N, Sandino A, Panthaki K Biomimetics (Basel). 2024; 9(11).

PMID: 39590262 PMC: 11592113. DOI: 10.3390/biomimetics9110690.

Trends in bioactivity: inducing and detecting mineralization of regenerative polymeric scaffolds.

Nitschke B, Beltran F, Hahn M, Grunlan M J Mater Chem B. 2024; 12(11):2720-2736.

PMID: 38410921 PMC: 10935659. DOI: 10.1039/d3tb02674d.

Injection of a PMMA-doped MSC spheroid gel for the treatment of painful osteoporotic vertebral compression fractures.

Ko W, Lee D, Kim S, Han G, Lee D, Sheen S Bioeng Transl Med. 2023; 8(6):e10577.

PMID: 38023703 PMC: 10658584. DOI: 10.1002/btm2.10577.

Nanomaterials Modulating the Fate of Dental-Derived Mesenchymal Stem Cells Involved in Oral Tissue Reconstruction: A Systematic Review.

Li X, Wang Y, Huang D, Jiang Z, He Z, Luo M Int J Nanomedicine. 2023; 18:5377-5406.

PMID: 37753067 PMC: 10519211. DOI: 10.2147/IJN.S418675.

References

Moshaverinia A, Xu X, Chen C, Ansari S, Zadeh H, Snead M . Application of stem cells derived from the periodontal ligament or gingival tissue sources for tendon tissue regeneration. Biomaterials. 2014; 35(9):2642-50. PMC: 3929697. DOI: 10.1016/j.biomaterials.2013.12.053. View

Kamitakahara M, Ohtsuki C, Miyazaki T . Review paper: behavior of ceramic biomaterials derived from tricalcium phosphate in physiological condition. J Biomater Appl. 2008; 23(3):197-212. DOI: 10.1177/0885328208096798. View

Langer R, Tirrell D . Designing materials for biology and medicine. Nature. 2004; 428(6982):487-92. DOI: 10.1038/nature02388. View

Wang M . Developing bioactive composite materials for tissue replacement. Biomaterials. 2003; 24(13):2133-51. DOI: 10.1016/s0142-9612(03)00037-1. View

Sivakumar M, Panduranga Rao K . Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite-gelatin composite microspheres. Biomaterials. 2002; 23(15):3175-81. DOI: 10.1016/s0142-9612(02)00066-2. View

Kohane D, Langer R . Polymeric biomaterials in tissue engineering. Pediatr Res. 2008; 63(5):487-91. DOI: 10.1203/01.pdr.0000305937.26105.e7. View

Niinomi M . Metallic biomaterials. J Artif Organs. 2008; 11(3):105-10. DOI: 10.1007/s10047-008-0422-7. View

Liu Y, Liu S, Luo D, Xue Z, Yang X, Gu L . Hierarchically Staggered Nanostructure of Mineralized Collagen as a Bone-Grafting Scaffold. Adv Mater. 2016; 28(39):8740-8748. DOI: 10.1002/adma.201602628. View

Tsumanuma Y, Iwata T, Washio K, Yoshida T, Yamada A, Takagi R . Comparison of different tissue-derived stem cell sheets for periodontal regeneration in a canine 1-wall defect model. Biomaterials. 2011; 32(25):5819-25. DOI: 10.1016/j.biomaterials.2011.04.071. View

10.

Wang S, Liu Y, Fang D, Shi S . The miniature pig: a useful large animal model for dental and orofacial research. Oral Dis. 2007; 13(6):530-7. DOI: 10.1111/j.1601-0825.2006.01337.x. View

11.

Liu Y, Luo D, Wang T . Hierarchical Structures of Bone and Bioinspired Bone Tissue Engineering. Small. 2016; 12(34):4611-32. DOI: 10.1002/smll.201600626. View

12.

Hsu F, Chueh S, Wang Y . Microspheres of hydroxyapatite/reconstituted collagen as supports for osteoblast cell growth. Biomaterials. 1999; 20(20):1931-6. DOI: 10.1016/s0142-9612(99)00095-2. View

13.

Liu S, Sun Y, Fu Y, Chang D, Fu C, Wang G . Bioinspired Collagen-Apatite Nanocomposites for Bone Regeneration. J Endod. 2016; 42(8):1226-32. DOI: 10.1016/j.joen.2016.04.027. View

14.

Liu Y, Li N, Qi Y, Dai L, Bryan T, Mao J . Intrafibrillar collagen mineralization produced by biomimetic hierarchical nanoapatite assembly. Adv Mater. 2011; 23(8):975-80. PMC: 3137871. DOI: 10.1002/adma.201003882. View

15.

Heino T, Alm J, Moritz N, Aro H . Comparison of the osteogenic capacity of minipig and human bone marrow-derived mesenchymal stem cells. J Orthop Res. 2012; 30(7):1019-25. DOI: 10.1002/jor.22049. View

16.

Wu L, Ding J . Effects of porosity and pore size on in vitro degradation of three-dimensional porous poly(D,L-lactide-co-glycolide) scaffolds for tissue engineering. J Biomed Mater Res A. 2005; 75(4):767-77. DOI: 10.1002/jbm.a.30487. View

17.

Janssens K, Ten Dijke P, Janssens S, Van Hul W . Transforming growth factor-beta1 to the bone. Endocr Rev. 2005; 26(6):743-74. DOI: 10.1210/er.2004-0001. View

18.

Ding G, Liu Y, Wang W, Wei F, Liu D, Fan Z . Allogeneic periodontal ligament stem cell therapy for periodontitis in swine. Stem Cells. 2010; 28(10):1829-38. PMC: 2996858. DOI: 10.1002/stem.512. View

19.

Kafantari H, Kounadi E, Fatouros M, Milonakis M, Tzaphlidou M . Structural alterations in rat skin and bone collagen fibrils induced by ovariectomy. Bone. 2000; 26(4):349-53. DOI: 10.1016/S8756-3282(99)00279-3. View

20.

Murphy C, Haugh M, OBrien F . The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. Biomaterials. 2009; 31(3):461-6. DOI: 10.1016/j.biomaterials.2009.09.063. View