Fabrication of gelatin methacrylate/nanohydroxyapatite microgel arrays for periodontal tissue regeneration.
BACKGROUND
Periodontitis is a chronic infectious disease and is the major cause of tooth loss and other oral health issues around the world. Periodontal tissue regeneration has therefore always been the ultimate goal of dentists and researchers. Existing fabrication methods mainly focused on a top-down tissue engineering strategy in which several drawbacks remain, including low throughput and limited diffusion properties resulting from a large sample size. Gelatin methacrylate (GelMA) is a kind of photocrosslinkable and biocompatible hydrogel, with the capacities of enabling cell encapsulation and regeneration of functional tissues. Here, we developed a novel method to fabricate GelMA/nanohydroxylapatite (nHA) microgel arrays using a photocrosslinkable strategy. The viability, proliferation, and osteogenic differentiation and in vivo osteogenesis of human periodontal ligament stem cells (hPDLSCs) encapsulated in microgels were evaluated. The results suggested that such microgels provide great potential for periodontal tissue repair and regeneration.


METHODS
Microgel arrays were fabricated by blending different weight ratios of GelMA and nHA. hPDLSCs were encapsulated in GelMA/nHA microgels of various ratios for a systematic evaluation of cell viability, proliferation, and osteogenic differentiation. In vivo osteogenesis in nude mice was also studied.


RESULTS
The GelMA/nHA microgels exhibited appropriate microarchitecture, mechanical strength, and surface roughness, thus enabling cell adhesion and proliferation. Additionally, the GelMA/nHA microgels (10%/2% w/v) enhanced the osteogenic differentiation of hPDLSCs by elevating the expression levels of osteogenic biomarker genes, such asALP,BSP,OCN, andRUNX2. In vivo ectopic transplantation results showed that GelMA/nHA microgels (10%/2% w/v) increased mineralized tissue formation with abundant vascularization, compared with the 1%, 3%, and the pure GelMA group.


CONCLUSIONS
The GelMA/nHA microgels (10%/2% w/v) facilitated hPDLSCs viability, proliferation, and osteogenic differentiation in vitro and further promoted new bone formation in vivo, suggesting that the GelMA/nHA microgels (10%/2% w/v) provide great potential for periodontal tissue regeneration.
State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics.
Xi
X
Chen
State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics.
Shizhu
S
Bai
State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Center for Tissue Engineering, School of Stomatology.
Bei
B
Li
State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics.
Huan
H
Liu
State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics.
Guofeng
G
Wu
Department of Plastic and Reconstructive Surgery, Xijing Hospital, The Fourth Military Medical University, Shaanxi, People's Republic of China.
Sha
S
Liu
State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics.
Yimin
Y
Zhao
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017886:Durapatite / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry*; D005782:Gels; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D023822:Tissue Engineering
D001672:Biocompatible Materials; D005782:Gels; D008689:Methacrylates; D005780:Gelatin; D017886:Durapatite
differentiation; gelatin methacrylate; microgel array; nanohydroxyapatite; periodontal ligament stem cells; periodontal tissue regeneration
Periodontol 2000. 2015 Jun;68(1):182-216
25867987
Biomaterials. 2013 Sep;34(29):7033-47
23768902
Bone. 2004 Aug;35(2):562-9
15268909
J Periodontal Res. 2015 Apr;50(2):160-72
24965968
Biomaterials. 2010 Jul;31(21):5536-44
20417964
Arch Oral Biol. 2014 Feb;59(2):158-66
24370187
Nat Biotechnol. 2003 May;21(5):513-8
12704396
Biomaterials. 2015 May;49:103-12
25725559
Biomaterials. 2012 Nov;33(31):7756-64
22841923
Biomaterials. 2014 Mar;35(9):2664-79
24411675
Biomaterials. 2015 Dec;73:254-71
26414409
Tissue Eng Part B Rev. 2013 Dec;19(6):485-502
23672709
Int J Nanomedicine. 2013;8:337-50
23345979
Int J Biol Macromol. 2013 Mar;54:24-9
23201776
Biomaterials. 2012 Oct;33(29):6974-86
22789721
ILAR J. 1997;38(1):41-48
11528046
J Mater Chem B. 2014 Mar 21;2(11):1584-1593
32261377
Biofabrication. 2014 Jun;6(2):024105
24695367
J Control Release. 2011 Jan 20;149(2):92-110
20974199
Biomaterials. 2014 Aug;35(24):6332-43
24824581
Sci Rep. 2016 Feb 18;6:19550
26887698
Cell Transplant. 2013;22(2):205-29
23031442
Crit Rev Biotechnol. 2016 Aug;36(4):760-75
26004052
Tissue Eng Part A. 2012 Mar;18(5-6):643-53
21981356
J Periodontol. 2011 Sep;82(9):1223-37
21284553
Biomaterials. 2014 Jul;35(20):5337-5346
24720878
Adv Drug Deliv Rev. 2014 Jul;74:95-103
24462454
Tissue Eng Part A. 2014 Feb;20(3-4):611-21
24070211