Babo, Pedro S.

Domingues, R.M.A.

Gomes, M.E.

Reis, R.L.

Rouwkema, J.

Silva, A.L.

Silva, C.R.

English

INTRODUCTION: Revascularization of pulp canal after endodontic treatment attains to rescue teeth from mid-term extraction fate, and can be promoted by the injection of hydrogels containing adequate cues. Herein are explored the proangiogenic effect of platelet-origin mediators modulated release [1] or hyaluronan oligomers instructive cues [2] within hydrogels aiming endodontic regeneration.METHODS: Hyaluronic acid (HA) hydrogels incorporating PL were produced by mixing 2% aldehyde-modified HA solution containing aldehyde-functionalized cellulose nanocrystals (CNCs) with 2% hydrazide- functionalized HA dissolved in human platelet lysate (PL). Were assessed the sprouting of human dental pulp cells (hDPCs) or DPCs/HUVECs 1:1 pellets encapsulated in the HA hydrogels, and the neovascularization in a chicken choriallantoic membrane (CAM) assay. Also, low (LMW) or high (HMW) molecular weight (6 kDa and 230 kDa; Lifecore) HA were immobilized over methacrylated gelatin hydrogels (GelMA) and the response of HUVECs in terms of viability and arrangement analyzed.RESULTS &amp; DISCUSSION: PL incorporation enhanced the sprouting of DPCs both in single and co-cultures (p&gt;0.001). Moreover, the combined effect of PL and DPCs encapsulation promoted the ingrowth of vascularized tissue into the hydrogels. The immobilization of LMW-HA over GelMA hydrogels enhanced the metabolic activity and promoted the organization of HUVECs into capilarlikestructures.CONCLUSIONS: Our findings from in vitro studies show that both the incorporation of humanoriginproangiogenic growth factors and the creation of instructive paths of HA oligomers within injectable hydrogels, might promote the revascularization required for endodontic regeneration.<br/

University of Twente Research Information

Find us at:www.termis.org/eu2019@termis_eu_2019termis@nuigalway.ieOrganized by:Laboratory of Biomaterialsin Tissue Engineering Organizing Secretariat:T:  +30 210 6833600 E:  congress@convin.gr W:  www.convin.gr27-31 May 2019Rhodes, GreeceRodos Palace HotelTERMIS EU 2019 Tissue Engineering Therapies:  From Concept to Clinical  Translation & CommercialisationConference Chair:  Dimitrios I. Zeugolis, PhDConference Program Chair:  Maria Chatzinikolaidou, PhD   1633 Revascularization promoted by platelet pro-angiogenic factors or hyaluronan oligomers – A step towards endodontic regeneration using injectable systems P.S. Babo1,2; C.R. Silva1,2; A.L. Silva1,2; R.M.A. Domingues1,2,3; J. Rouwkema4; R.L. Reis1,2,3; M.E. Gomes1,2,3 Presenting Author: Rui MA Domingues, rui.domingues@i3bs.uminho.pt 1B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal 2ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães 4805-017, Portugal 4Department of Biomechanical Engineering, Faculty of Engineering Technology, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands 3The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal  INTRODUCTION: Revascularization of pulp canal after endodontic treatment attains to rescue teeth from mid-term extraction fate, and can be promoted by the injection of hydrogels containing adequate cues. Herein are explored the proangiogenic effect of platelet-origin mediators modulated release [1] or hyaluronan oligomers instructive cues [2] within hydrogels aiming endodontic regeneration.  METHODS: Hyaluronic acid (HA) hydrogels incorporating PL were produced by mixing 2% aldehyde-modified HA solution containing aldehyde-functionalized cellulose nanocrystals (CNCs) with 2% hydrazide- functionalized HA dissolved in human platelet lysate (PL). Were assessed the sprouting of human dental pulp cells (hDPCs) or DPCs/HUVECs 1:1 pellets encapsulated in the HA hydrogels, and the neovascularization in a chicken choriallantoic membrane (CAM) assay. Also, low (LMW) or high (HMW) molecular weight (6 kDa and 230 kDa; Lifecore) HA were immobilized over methacrylated gelatin hydrogels (GelMA) and the response of HUVECs in terms of viability and arrangement analyzed.  RESULTS & DISCUSSION: PL incorporation enhanced the sprouting of DPCs both in single and co-cultures (p>0.001). Moreover, the combined effect of PL and DPCs encapsulation promoted the ingrowth of vascularized tissue into the hydrogels. The immobilization of LMW-HA over GelMA hydrogels enhanced the metabolic activity and promoted the organization of HUVECs into capilar-like structures.  CONCLUSIONS: Our findings from in vitro studies show that both the incorporation of human-origin proangiogenic growth factors and the creation of instructive paths of HA oligomers within injectable hydrogels, might promote the revascularization required for endodontic regeneration.  ACKNOWLEDGEMENTS: Financial support from FCT (UTAP-ICDT/CTM-BIO/0023/2014; RMAD grant SFRH/BPD/112459/2015; PSB grant from project PTDC/CTM-BIO/4706/2014-POCI-01-0145-FEDER 016716); and ERDF NORTE-01-0145-FEDER-000021. SH-CHSJ (Porto, Portugal) for the platelet concentrate batches.  REFERENCES [1] Fortunato TM et al. Sci Rep. 2016;6(1):25326 [2] Slevin M et al. J Biol Chem. 2002;277(43):41046–59  

Revascularization promoted by platelet pro-angiogenic factors or hyaluronan oligomers – A step towards endodontic regeneration using injectable systems

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Revascularization promoted by platelet pro-angiogenic factors or hyaluronan oligomers – A step towards endodontic regeneration using injectable systems

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