Jun Zhang1, Yong-Duk Park2, Won-Jung Bae1, Ahmed El-Fiqi3, Song-Hee Shin3, Eun-Jung Lee3, Hae-Won Kim4, Eun-Cheol Kim5. 1. Department of Maxillofacial Tissue Regeneration, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea. 2. Department of Preventive and Society Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea. 3. College of Dentistry & Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea. 4. College of Dentistry & Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea kimhw@dku.edu. 5. Department of Maxillofacial Tissue Regeneration, and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea eckim@khu.ac.kr.
Abstract
BACKGROUND: The objective of this study was to investigate the effects of bioactive calcium phosphate cements (CPC, α-tricalcium phosphate-based) incorporating zinc-bioglass (ZnBG) on the odontogenic differentiation and angiogenesis of human dental pulp cells (HDPCs). METHODS: BGs with varying concentrations of Zn (0, 2.5 and 5%) were produced via a sol-gel process. The proliferation of HDPCs on CPC/BGs was determined by MTS assay. Alizarin red staining, RT-PCR, and ALP activity were used to assess odontogenic differentiation, and western blot analysis was used to asses signaling pathways. In vitro angiogenesis was examined via mRNA expression of angiogenic genes and tubule formation. RESULTS: All cement formulations showed no cytotoxicity. The CPCs with ZnBG showed increased ALP activity, enhanced formation of mineralized nodules, and upregulated mRNA expression of DMP-1, DSPP, Runx2, and osterix in a time- and dose-dependent manner, relative to CPCs without Zn. ZnBG upregulated integrins α1, α2, β1, and β3 and activated integrin downstream signal pathways, such as p-FAK, p-Akt, p-paxillin, RhoA, MAPK, and NF-κB, as well as canonical and non-canonical Wnt signaling. In addition, ZnBG upregulated VEGF mRNA in HDPCs and increased the tubular structure in endothelial cells. CONCLUSIONS: Our results demonstrate that ZnBG incorporated within CPCs activates odontogenic differentiation and promotes angiogenesis in vitro through integrin, Wnt, MAPK, and NF-κB pathways. Thus, CPCs incorporating ZnBG are promising matrices in tissue engineering to stimulate endodontic regeneration.
BACKGROUND: The objective of this study was to investigate the effects of bioactive calcium phosphate cements (CPC, α-tricalcium phosphate-based) incorporating zinc-bioglass (ZnBG) on the odontogenic differentiation and angiogenesis of human dental pulp cells (HDPCs). METHODS: BGs with varying concentrations of Zn (0, 2.5 and 5%) were produced via a sol-gel process. The proliferation of HDPCs on CPC/BGs was determined by MTS assay. Alizarin red staining, RT-PCR, and ALP activity were used to assess odontogenic differentiation, and western blot analysis was used to asses signaling pathways. In vitro angiogenesis was examined via mRNA expression of angiogenic genes and tubule formation. RESULTS: All cement formulations showed no cytotoxicity. The CPCs with ZnBG showed increased ALP activity, enhanced formation of mineralized nodules, and upregulated mRNA expression of DMP-1, DSPP, Runx2, and osterix in a time- and dose-dependent manner, relative to CPCs without Zn. ZnBG upregulated integrins α1, α2, β1, and β3 and activated integrin downstream signal pathways, such as p-FAK, p-Akt, p-paxillin, RhoA, MAPK, and NF-κB, as well as canonical and non-canonical Wnt signaling. In addition, ZnBG upregulated VEGF mRNA in HDPCs and increased the tubular structure in endothelial cells. CONCLUSIONS: Our results demonstrate that ZnBG incorporated within CPCs activates odontogenic differentiation and promotes angiogenesis in vitro through integrin, Wnt, MAPK, and NF-κB pathways. Thus, CPCs incorporating ZnBG are promising matrices in tissue engineering to stimulate endodontic regeneration.
Authors: C Pushpalatha; Jithya Suresh; V S Gayathri; S V Sowmya; Dominic Augustine; Ahmed Alamoudi; Bassam Zidane; Nassreen Hassan Mohammad Albar; Shankargouda Patil Journal: Front Bioeng Biotechnol Date: 2022-05-19
Authors: Samer Al-Saleh; Turki W Aboghosh; Mousa S Hazazi; Khalid A Binsaeed; Abdulaziz M Almuhaisen; Huda I Tulbah; Amal S Al-Qahtani; Sara Shabib; Mashael Binhasan; Fahim Vohra; Tariq Abduljabbar Journal: Polymers (Basel) Date: 2021-12-02 Impact factor: 4.329