Current Stem Cell Research & TherapyCurrent Stem Cell Research & TherapyCurrent Stem Cell Research & Therapy1574-888X2212-3946Bentham Science64578510.2174/1574888X18666221227142055MedicineResearch ArticleBone Scaffold Materials in Periodontal and Tooth-supporting Tissue Regeneration: A ReviewJahangirnezhadMahmoodinfo@benthamscience.netMahmoudinezhadSadafinfo@benthamscience.netMoradiMelikainfo@benthamscience.netMoradiKooshaninfo@benthamscience.netRohaniAliinfo@benthamscience.netTayebiLobatinfo@benthamscience.netDepartment of Periodontics, School of Dentistry, Ahvaz Jundishapur University of Medical SciencesSchool of Dentistry, Marquette University0104202419444946011012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://journals.eco-vector.com/1574-888X/article/view/645785

Background and Objectives:Periodontium is an important tooth-supporting tissue composed of both hard (alveolar bone and cementum) and soft (gingival and periodontal ligament) sections. Due to the multi-tissue architecture of periodontium, reconstruction of each part can be influenced by others. This review focuses on the bone section of the periodontium and presents the materials used in tissue engineering scaffolds for its reconstruction.

Materials and Methods:The following databases (2015 to 2021) were electronically searched: ProQuest, EMBASE, SciFinder, MRS Online Proceedings Library, Medline, and Compendex. The search was limited to English-language publications and in vivo studies.

Results:Eighty-three articles were found in primary searching. After applying the inclusion criteria, seventeen articles were incorporated into this study.

Conclusions:In complex periodontal defects, various types of scaffolds, including multilayered ones, have been used for the functional reconstruction of different parts of periodontium. While there are some multilayered scaffolds designed to regenerate alveolar bone/periodontal ligament/cementum tissues of periodontium in a hierarchically organized construct, no scaffold could so far consider all four tissues involved in a complete periodontal defect. The progress and material considerations in the regeneration of the bony part of periodontium are presented in this work to help investigators develop tissue engineering scaffolds suitable for complete periodontal regeneration.

Bone scaffoldperiodontal regenerationperiodontal tissue engineeringbone regeneration materialsprogenitor cellsperiodontal ligament.Peres MA, Macpherson LMD, Weyant RJ, et al. Oral diseases: a global public health challenge. Lancet 2019; 394(10194): 249-60. doi: 10.1016/S0140-6736(19)31146-8 PMID: 31327369Frencken JE, Sharma P, Stenhouse L, Green D, Laverty D, Dietrich T. Global epidemiology of dental caries and severe periodontitis - a comprehensive review. J Clin Periodontol 2017; 44 (Suppl. 18): S94-S105. doi: 10.1111/jcpe.12677 PMID: 28266116Woo HN, Cho YJ, Tarafder S, Lee CH. The recent advances in scaffolds for integrated periodontal regeneration. Bioact Mater 2021; 6(10): 3328-42. doi: 10.1016/j.bioactmat.2021.03.012 PMID: 33817414Bottino MC, Thomas V, Schmidt G, et al. Recent advances in the development of GTR/GBR membranes for periodontal regeneration—A materials perspective. Dent Mater 2012; 28(7): 703-21. doi: 10.1016/j.dental.2012.04.022 PMID: 22592164Liang Y, Luan X, Liu X. Recent advances in periodontal regeneration: A biomaterial perspective. Bioact Mater 2020; 5(2): 297-308. doi: 10.1016/j.bioactmat.2020.02.012 PMID: 32154444Hasani-Sadrabadi MM, Sarrion P, Nakatsuka N, et al. Hierarchically patterned polydopamine-containingmembranesfor periodontal tissue engineering. ACS Nano 2019; 13(4): 3830-8. doi: 10.1021/acsnano.8b09623 PMID: 30895772Tan J, Zhang M, Hai Z, et al. Sustained release of two bioactive factors from supramolecular hydrogel promotes periodontal bone regeneration. ACS Nano 2019; 13(5): 5616-22. doi: 10.1021/acsnano.9b00788 PMID: 31059238Aytac Z, Dubey N, Daghrery A, et al. Innovations in craniofacial bone and periodontal tissueengineering–fromelectrospinning to converged biofabrication. Int Mater Rev 2021; 67(4): 347-84. PMID: 35754978Kao RT, Murakami S, Beirne OR. The use of biologic mediators and tissue engineering in dentistry. Periodontol 2000 2009; 50(1): 127-53. doi: 10.1111/j.1600-0757.2008.00287.x PMID: 19388957Dabra S, Chhina K, Soni N, Bhatnagar R. Tissue engineering in periodontal regeneration: A brief review. Dent Res J (Isfahan) 2012; 9(6): 671-80. PMID: 23559940Oldham JB, Lu L, Zhu X, Porter BD, Hefferan TE, Larson DR, et al. Biological activity of rhBMP-2 released from PLGA microspheres. J Biomech Eng 2000; 122(3): 289-92. Available from: doi: 10.1115/1.429662Henkel J, Woodruff MA, Epari DR, et al. Bone regeneration based on tissue engineering conceptions—a 21st century perspective. Bone Res 2013; 1(3): 216-48. doi: 10.4248/BR201303002 PMID: 26273505Wang CY, Chiu YC, Lee AKX, Lin YA, Lin PY, Shie MY. Biofabrication of gingival fibroblast cell-laden collagen/strontium-doped calcium silicate 3D-printed bi-layered scaffold for osteoporotic periodontal regeneration. Biomedicines 2021; 9(4): 431. doi: 10.3390/biomedicines9040431 PMID: 33923505Smith BD, Grande DA. The current state of scaffolds for musculoskeletal regenerative applications. Nat Rev Rheumatol 2015; 11(4): 213-22. doi: 10.1038/nrrheum.2015.27 PMID: 25776947Chen FM, Liu X. Advancing biomaterials of human origin for tissue engineering. Prog Polym Sci 2016; 53: 86-168. doi: 10.1016/j.progpolymsci.2015.02.004 PMID: 27022202Park SB, Lih E, Park KS, Joung YK, Han DK. Biopolymer-based functional composites for medical applications. Prog Polym Sci 2017; 68: 77-105. doi: 10.1016/j.progpolymsci.2016.12.003Stoppel WL, Ghezzi CE, McNamara SL, Iii LDB, Kaplan DL. Clinical applications of naturally derived biopolymer-based scaffolds for regenerative medicine. Ann Biomed Eng 2015; 43(3): 657-80. doi: 10.1007/s10439-014-1206-2 PMID: 25537688Hussey GS, Dziki JL, Badylak SF. Extracellular matrix-based materials for regenerative medicine. Nat Rev Mater 2018; 3(7): 159-73. doi: 10.1038/s41578-018-0023-xChan G, Mooney DJ. New materials for tissue engineering: towards greater control over the biological response. Trends Biotechnol 2008; 26(7): 382-92. doi: 10.1016/j.tibtech.2008.03.011 PMID: 18501452Zhuang Y, Lin K, Yu H. Advance of nano-composite electrospun fibers in periodontal regeneration. Front Chem 2019; 7: 495. doi: 10.3389/fchem.2019.00495 PMID: 31355186Zhu L, Luo D, Liu Y. Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration. Int J Oral Sci 2020; 12(1): 6. doi: 10.1038/s41368-020-0073-y PMID: 32024822Tcacencu I, Rodrigues N, Alharbi N, et al. Osseointegration of porous apatite-wollastonite and poly(lactic acid) composite structures created using 3D printing techniques. Mater Sci Eng C 2018; 90: 1-7. doi: 10.1016/j.msec.2018.04.022 PMID: 29853072Chen Q, Zhu C, Thouas GA. Progress and challenges in biomaterials used for bone tissue engineering: bioactive glasses and elastomeric composites. Prog Biomater 2012; 1(1): 2. doi: 10.1186/2194-0517-1-2 PMID: 29470743Abbasi N, Hamlet S, Dau VT, Nguyen N-T. Calcium phosphate stability on melt electrowritten PCL scaffolds. J Sci Adv Mater Devices 2020; 5(1): 30-9. doi: 10.1016/j.jsamd.2020.01.001Liu J, Jin T, Chang S, et al. The effect of novel fluorapatite surfaces on osteoblast-like cell adhesion, growth, and mineralization. Tissue Eng Part A 2010; 16(9): 2977-86. doi: 10.1089/ten.tea.2009.0632 PMID: 20412028Bartold PM, Gronthos S, Ivanovski S, Fisher A, Hutmacher DW. Tissue engineered periodontal products. J Periodontal Res 2016; 51(1): 1-15. doi: 10.1111/jre.12275 PMID: 25900048Rasperini G, Pilipchuk SP, Flanagan CL, et al. 3D-printed bioresorbable scaffold for periodontal repair. J Dent Res 2015; 94 (Suppl. 9): 153S-7S. doi: 10.1177/0022034515588303 PMID: 26124215Yilgor P, Sousa RA, Reis RL, Hasirci N, Hasirci V. 3D plotted PCL scaffolds for stem cell based bone tissue engineering. Macromol Symp 2008; 269(1): 92-9.Dwivedi R, Kumar S, Pandey R, et al. Polycaprolactone as biomaterial for bone scaffolds: Review of literature. J Oral Biol Craniofac Res 2020; 10(1): 381-8. doi: 10.1016/j.jobcr.2019.10.003 PMID: 31754598Rotbaum Y, Puiu C, Rittel D, Domingos M. Quasi-static and dynamic in vitro mechanical response of 3D printed scaffolds with tailored pore size and architectures. Mater Sci Eng C 2019; 96: 176-82. doi: 10.1016/j.msec.2018.11.019 PMID: 30606523Kashirina A, Yao Y, Liu Y, Leng J. Biopolymers as bone substitutes: a review. Biomater Sci 2019; 7(10): 3961-83. doi: 10.1039/C9BM00664H PMID: 31364613Bayani M, Torabi S, Shahnaz A, Pourali M. Main properties of nanocrystalline hydroxyapatite as a bone graft material in treatment of periodontal defects. A review of literature. Biotechnol Biotechnol Equip 2017; 31(2): 215-20. doi: 10.1080/13102818.2017.1281760Brunello G, Panda S, Schiavon L, Sivolella S, Biasetto L, Del Fabbro M. The impact of bioceramic scaffolds on bone regeneration in preclinical in vivo studies: a systematic review. Materials (Basel) 2020; 13(7): 1500. doi: 10.3390/ma13071500 PMID: 32218290Salinas AJ, Esbrit P, Vallet-Regí M. A tissue engineering approach based on the use of bioceramics for bone repair. Biomater Sci 2013; 1(1): 40-51. doi: 10.1039/C2BM00071G PMID: 32481996Mancuso E, Bretcanu OA, Marshall M, Birch MA, McCaskie AW, Dalgarno KW. Novel bioglasses for bone tissue repair and regeneration: Effect of glass design on sintering ability, ion release and biocompatibility. Mater Des 2017; 129: 239-48. doi: 10.1016/j.matdes.2017.05.037 PMID: 28883669Carter SSD, Costa PF, Vaquette C, Ivanovski S, Hutmacher DW, Malda J. Additive biomanufacturing: an advancedapproach for periodontal tissue regeneration. Ann Biomed Eng 2017; 45(1): 12-22. doi: 10.1007/s10439-016-1687-2 PMID: 27473707Eap S, Ferrand A, Mendoza Palomares C, et al. Electrospun nanofibrous 3D scaffold for bone tissue engineering. Biomed Mater Eng 2012; 22(1-3): 137-41. doi: 10.3233/BME-2012-0699 PMID: 22766712Vaquette C, Fan W, Xiao Y, Hamlet S, Hutmacher DW, Ivanovski S. A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone/periodontal ligament complex. Biomaterials 2012; 33(22): 5560-73. doi: 10.1016/j.biomaterials.2012.04.038 PMID: 22575832Farag A, Vaquette C, Theodoropoulos C, Hamlet SM, Hutmacher DW, Ivanovski S. Decellularized periodontal ligament cell sheets with recellularization potential. J Dent Res 2014; 93(12): 1313-9. doi: 10.1177/0022034514547762 PMID: 25270757Eap S, Keller L, Schiavi J, et al. A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration. Int J Nanomedicine 2015; 10: 1061-75. PMID: 25709432Mathew A, Vaquette C, Hashimi S, et al. Antimicrobial and immunomodulatory surface‐functionalized electrospun membranes for bone regeneration. Adv Healthc Mater 2017; 6(10): 1601345. doi: 10.1002/adhm.201601345 PMID: 28240815Ferrand A, Eap S, Richert L, et al. Osteogenetic properties of electrospun nanofibrous PCL scaffolds equipped with chitosan-based nanoreservoirs of growth factors. Macromol Biosci 2014; 14(1): 45-55. doi: 10.1002/mabi.201300283 PMID: 23956214Ren K, Wang Y, Sun T, Yue W, Zhang H. Electrospun PCL/gelatin composite nanofiber structures for effective guided bone regeneration membranes. Mater Sci Eng C 2017; 78: 324-32. doi: 10.1016/j.msec.2017.04.084 PMID: 28575991Lam CXF, Savalani MM, Teoh SH, Hutmacher DW. Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds: accelerated versus simulated physiological conditions. Biomed Mater 2008; 3(3): 034108. doi: 10.1088/1748-6041/3/3/034108 PMID: 18689929Woodruff MA, Hutmacher DW. The return of a forgotten polymer—Polycaprolactone in the 21st century. Prog Polym Sci 2010; 35(10): 1217-56. doi: 10.1016/j.progpolymsci.2010.04.002Campbell JH, Efendy JL, Campbell GR. Novel vascular graft grown within recipient’s own peritoneal cavity. Circ Res 1999; 85(12): 1173-8. doi: 10.1161/01.RES.85.12.1173 PMID: 10590244Kim CH, Khil MS, Kim HY, Lee HU, Jahng KY. An improved hydrophilicity via electrospinning for enhanced cell attachment and proliferation. J Biomed Mater Res B Appl Biomater 2006; 78B(2): 283-90. doi: 10.1002/jbm.b.30484 PMID: 16362963Fabbri P, Bondioli F, Messori M, Bartoli C, Dinucci D, Chiellini F. Porous scaffolds of polycaprolactone reinforced with in situ generated hydroxyapatite for bone tissue engineering. J Mater Sci Mater Med 2010; 21(1): 343-51. doi: 10.1007/s10856-009-3839-5 PMID: 19653069Chen JP, Chang YS. Preparation and characterization of composite nanofibers of polycaprolactone and nanohydroxyapatite for osteogenic differentiation of mesenchymal stem cells. Colloids Surf B Biointerfaces 2011; 86(1): 169-75. doi: 10.1016/j.colsurfb.2011.03.038 PMID: 21514800Hassan MI, Sultana N. Characterization, drug loading and antibacterial activity of nanohydroxyapatite/polycaprolactone (nHA/PCL) electrospun membrane. 3 Biotech 2017; 7(4): 1-9.Groppo MF, Caria PH, Freire AR, et al. The effect of a hydroxyapatite impregnated PCL membrane in rat subcritical calvarial bone defects. Arch Oral Biol 2017; 82: 209-15. doi: 10.1016/j.archoralbio.2017.06.018 PMID: 28651093Park SH, Kim TI, Ku Y, et al. Effect of hydroxyapatite-coated nanofibrous membrane on the responses of human periodontal ligament fibroblast. J Ceram Soc Jpn 2008; 116(1349): 31-5. doi: 10.2109/jcersj2.116.31Peng F, Yu X, Wei M. In vitro cell performance on hydroxyapatite particles/poly(l-lactic acid) nanofibrous scaffolds with an excellent particle along nanofiber orientation. Acta Biomater 2011; 7(6): 2585-92. doi: 10.1016/j.actbio.2011.02.021 PMID: 21333762Chiara G, Letizia F, Lorenzo F, et al. Nanostructured biomaterials for tissue engineered bone tissue reconstruction. Int J Mol Sci 2012; 13(1): 737-57. doi: 10.3390/ijms13010737 PMID: 22312283Kasaj A, Willershausen B, Reichert C, Röhrig B, Smeets R, Schmidt M. Ability of nanocrystalline hydroxyapatite paste to promote human periodontal ligament cell proliferation. J Oral Sci 2008; 50(3): 279-85. doi: 10.2334/josnusd.50.279 PMID: 18818463Higuchi J, Fortunato G, Woźniak B, et al. Polymer membranes sonocoated and electrosprayed with nano-hydroxyapatite for periodontal tissues regeneration. Nanomaterials (Basel) 2019; 9(11): 1625. doi: 10.3390/nano9111625 PMID: 31731775Sattary M, Khorasani MT, Rafienia M, Rozve HS. Incorporation of nanohydroxyapatite and vitamin D3 into electrospun PCL/Gelatin scaffolds: The influence on the physical and chemical properties and cell behavior for bone tissue engineering. Polym Adv Technol 2018; 29(1): 451-62. doi: 10.1002/pat.4134Kanaya S, Nemoto E, Sakisaka Y, Shimauchi H. Calcium-mediated increased expression of fibroblast growth factor-2 acts through NF-κB and PGE2/EP4 receptor signaling pathways in cementoblasts. Bone 2013; 56(2): 398-405. doi: 10.1016/j.bone.2013.06.031 PMID: 23851295Roopavath UK, Malferrari S, Van Haver A, Verstreken F, Rath SN, Kalaskar DM. Optimization of extrusion based ceramic 3D printing process for complex bony designs. Mater Des 2019; 162: 263-70. doi: 10.1016/j.matdes.2018.11.054Ye X, Leeflang S, Wu C, Chang J, Zhou J, Huan Z. Mesoporous bioactive glass functionalized 3D Ti-6Al-4V scaffolds with improved surface bioactivity. Materials (Basel) 2017; 10(11): 1244. doi: 10.3390/ma10111244 PMID: 29077014Chai YC, Carlier A, Bolander J, et al. Current views on calcium phosphate osteogenicity and the translation into effective bone regeneration strategies. Acta Biomater 2012; 8(11): 3876-87. doi: 10.1016/j.actbio.2012.07.002 PMID: 22796326Shimauchi H, Nemoto E, Ishihata H, Shimomura M. Possible functional scaffolds for periodontal regeneration. Jpn Dent Sci Rev 2013; 49(4): 118-30. doi: 10.1016/j.jdsr.2013.05.001Tada H, Nemoto E, Kanaya S, Hamaji N, Sato H, Shimauchi H. Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells. Biochem Biophys Res Commun 2010; 394(4): 1093-7. doi: 10.1016/j.bbrc.2010.03.135 PMID: 20346918(a) Bouhadir KH, Lee KY, Alsberg E, Damm KL, Anderson KW, Mooney DJ. Degradation of partially oxidized alginate and its potential application for tissue engineering. Biotechnol Prog 2001; 17(5): 945-50. doi: 10.1021/bp010070p PMID: 11587588; (b) Shirafkan S, Gholamian M, Rohani A, Mahmoudinezhad SS, Razavi M, Moradi K. Complete Spontaneous Bone Regeneration following Surgical Enucleation of a Mandibular Cemento-Ossifying Fibroma. Case Rep Dent 2022. Aug 5; 2022.Drury JL, Mooney DJ. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 2003; 24(24): 4337-51. doi: 10.1016/S0142-9612(03)00340-5 PMID: 12922147Li L, Davidovich AE, Schloss JM, et al. Neural lineage differentiation of embryonic stem cells within alginate microbeads. Biomaterials 2011; 32(20): 4489-97. doi: 10.1016/j.biomaterials.2011.03.019 PMID: 21481927Liu J, Sato C, Cerletti M, Wagers A. Notch signaling in the regulation of stem cell self-renewal and differentiation. Curr Top Dev Biol 2010; 92: 367-409. doi: 10.1016/S0070-2153(10)92012-7 PMID: 20816402Kratchmarova I, Blagoev B, Haack-Sorensen M, Kassem M, Mann M. Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation. Science 2005; 308(5727): 1472-7. doi: 10.1126/science.1107627 PMID: 15933201Cantu DA, Hematti P, Kao WJ. Cell encapsulating biomaterial regulates mesenchymal stromal/stem cell differentiation and macrophage immunophenotype. Stem Cells Transl Med 2012; 1(10): 740-9. doi: 10.5966/sctm.2012-0061 PMID: 23197666Ansari S, Moshaverinia A, Han A, Pi SP, Abdelhamid AI, Zadeh HH. Biomaterials 2013; 34: 0191.Moshaverinia A, Chen C, Akiyama K, et al. Encapsulated dental-derived mesenchymal stem cells in an injectable and biodegradable scaffold for applications in bone tissue engineering. J Biomed Mater Res A 2013; 101(11): 3285-94. doi: 10.1002/jbm.a.34546 PMID: 23983201Moshaverinia A, Chen C, Akiyama K, et al. Alginate hydrogel as a promising scaffold for dental-derived stem cells: An in vitro study. J Mater Sci Mater Med 2012; 23(12): 3041-51. doi: 10.1007/s10856-012-4759-3 PMID: 22945383Ansari S, Chen C, Xu X, et al. Muscle tissue engineering using gingival mesenchymal stem cells encapsulated in alginate hydrogels containing multiple growth factors. Ann Biomed Eng 2016; 44(6): 1908-20. doi: 10.1007/s10439-016-1594-6 PMID: 27009085Margolis RU, Margolis RK, Chang LB, Preti C. Glycosaminoglycans of brain during development. Biochemistry 1975; 14(1): 85-8. doi: 10.1021/bi00672a014 PMID: 122810Preston M, Sherman LS. Neural stem cell niches: critical roles for the hyaluronan-based extracellular matrix inneural stem cell proliferation and differentiation. Front Biosci (Schol Ed) 2012; 3: 1165. PMID: 21622263Bandtlow CE, Zimmermann DR. Proteoglycans in the developing brain: New conceptual insights for old proteins. Physiol Rev 2000; 80(4): 1267-90. doi: 10.1152/physrev.2000.80.4.1267 PMID: 11015614Knudson CB. Hyaluronan and CD44: Strategic players for cell-matrix interactions during chondrogenesis and matrix assembly. Birth Defects Res C Embryo Today 2003; 69(2): 174-96. doi: 10.1002/bdrc.10013 PMID: 12955860Huang KH, Wang CY, Chen CY, Hsu TT, Lin CP. Incorporation of calcium sulfate dihydrate into a mesoporous calcium silicate/poly-ε-caprolactone scaffold to regulate the release of bone morphogenetic protein-2 and accelerate bone regeneration. Biomedicines 2021; 9(2): 128. doi: 10.3390/biomedicines9020128 PMID: 33572786Seol YJ, Kim KH, Kang YM, Kim IA, Rhee SH. Bioactivity, pre-osteoblastic cell responses, and osteoconductivity evaluations of the electrospun non-woven SiO 2 -CaO gel fabrics. J Biomed Mater Res B Appl Biomater 2009; 90B(2): 679-87. doi: 10.1002/jbm.b.31334 PMID: 19213049Münchow EA, Albuquerque MTP, Zero B, et al. Development and characterization of novel ZnO-loaded electrospun membranes for periodontal regeneration. Dent Mater 2015; 31(9): 1038-51. doi: 10.1016/j.dental.2015.06.004 PMID: 26116414Münchow EA, Pankajakshan D, Albuquerque MTP, et al. Synthesis and characterization of CaO-loaded electrospun matrices for bone tissue engineering. Clin Oral Investig 2016; 20(8): 1921-33. doi: 10.1007/s00784-015-1671-5 PMID: 26612403Yu CT, Wang FM, Liu YT, et al. Effect of bone morphogenic protein-2-loaded mesoporous strontium substitution calcium silicate/recycled fish gelatin 3D Cell-Laden scaffold for bone tissue engineering. Processes (Basel) 2020; 8(4): 493. doi: 10.3390/pr8040493Lee SH, Lee KG, Hwang JH, et al. Evaluation of mechanical strength and bone regeneration ability of 3D printed kagome-structure scaffold using rabbit calvarial defect model. Mater Sci Eng C 2019; 98: 949-59. doi: 10.1016/j.msec.2019.01.050 PMID: 30813102Huang TH, Kao CT, Shen YF, et al. Substitutions of strontium in bioactive calcium silicate bone cements stimulate osteogenic differentiation in human mesenchymal stem cells. J Mater Sci Mater Med 2019; 30(6): 68. doi: 10.1007/s10856-019-6274-2 PMID: 31165270Zhang S, Dong Y, Chen M, et al. Recent developments in strontium-based biocomposites for bone regeneration. J Artif Organs 2020; 23(3): 191-202. doi: 10.1007/s10047-020-01159-y PMID: 32100147Ni GX, Shu B, Huang G, Lu WW, Pan HB. The effect of strontium incorporation into hydroxyapatites on their physical and biological properties. J Biomed Mater Res B Appl Biomater 2012; 100B(2): 562-8. doi: 10.1002/jbm.b.31986 PMID: 22114002Pierantozzi D, Scalzone A, Jindal S, et al. 3D printed Sr-containing composite scaffolds: Effect of structural design and material formulation towards new strategies for bone tissue engineering. Compos Sci Technol 2020; 191: 108069. doi: 10.1016/j.compscitech.2020.108069Panzavolta S, Torricelli P, Casolari S, Parrilli A, Fini M, Bigi A. Strontium‐substituted hydroxyapatite‐gelatin biomimetic scaffolds modulate bone cell response. Macromol Biosci 2018; 18(7): 1800096. doi: 10.1002/mabi.201800096 PMID: 29877029Saidak Z, Marie PJ. Strontium signaling: Molecular mechanisms and therapeutic implications in osteoporosis. Pharmacol Ther 2012; 136(2): 216-26. doi: 10.1016/j.pharmthera.2012.07.009 PMID: 22820094Zhang W, Shen Y, Pan H, et al. Effects of strontium in modified biomaterials. Acta Biomater 2011; 7(2): 800-8. doi: 10.1016/j.actbio.2010.08.031 PMID: 20826233Liu D, Nie W, Li D, et al. 3D printed PCL/SrHA scaffold for enhanced bone regeneration. Chem Eng J 2019; 362: 269-79. doi: 10.1016/j.cej.2019.01.015Lin YH, Chiu YC, Shen YF, Wu YHA, Shie MY. Bioactive calcium silicate/poly-ε-caprolactone composite scaffolds 3D printed under mild conditions for bone tissue engineering. J Mater Sci Mater Med 2018; 29(1): 11. doi: 10.1007/s10856-017-6020-6 PMID: 29282550Vijaykumar A, Dyrkacz P, Vidovic-Zdrilic I, Maye P, Mina M. Expression of BSP-GFPtpz transgene during osteogenesis and reparative dentinogenesis. J Dent Res 2020; 99(1): 89-97. doi: 10.1177/0022034519885089 PMID: 31682548He F, Lu T, Fang X, et al. Effects of strontium amount on the mechanical strength and cell-biological performance of magnesium-strontium phosphate bioceramics for bone regeneration. Mater Sci Eng C 2020; 112: 110892. doi: 10.1016/j.msec.2020.110892 PMID: 32409050Daghrery A, Ferreira JA, de Souza Araújo IJ, et al. A highly ordered, nanostructured fluorinated CaP‐Coated melt electrowritten scaffold for periodontal tissue regeneration. Adv Healthc Mater 2021; 10(21): 2101152. doi: 10.1002/adhm.202101152 PMID: 34342173Abbasi N, Abdal-hay A, Hamlet S, Graham E, Ivanovski S. Effects of gradient and offset architectures on the mechanical and biological properties of 3-D melt electrowritten (MEW) scaffolds. ACS Biomater Sci Eng 2019; 5(7): 3448-61. doi: 10.1021/acsbiomaterials.8b01456 PMID: 33405729Vaquette C, Ivanovski S, Hamlet SM, Hutmacher DW. Effect of culture conditions and calcium phosphate coating on ectopic bone formation. Biomaterials 2013; 34(22): 5538-51. doi: 10.1016/j.biomaterials.2013.03.088 PMID: 23623428Ge X, Leng Y, Bao C, Xu SL, Wang R, Ren F. Antibacterial coatings of fluoridated hydroxyapatite for percutaneous implants. J Biomed Mater Res A 2010; 95A(2): 588-99. doi: 10.1002/jbm.a.32862 PMID: 20725973Bozza A, Coates EE, Incitti T, et al. Neural differentiation of pluripotent cells in 3D alginate-based cultures. Biomaterials 2014; 35(16): 4636-45. doi: 10.1016/j.biomaterials.2014.02.039 PMID: 24631250Nandakumar A, Yang L, Habibovic P, van Blitterswijk C. Calcium phosphate coated electrospun fiber matrices as scaffolds for bone tissue engineering. Langmuir 2010; 26(10): 7380-7. doi: 10.1021/la904406b PMID: 20039599Sundararaj SC, Thomas MV, Peyyala R, Dziubla TD, Puleo DA. Design of a multiple drug delivery system directed at periodontitis. Biomaterials 2013; 34(34): 8835-42. doi: 10.1016/j.biomaterials.2013.07.093 PMID: 23948165Brager U, Mühle T, Fourmousis L, Lang NP, Mombelli A. Effect of the NSAID flurbiprofen on remodelling after periodontal surgery. J Periodontal Res 1997; 32(7): 575-82. doi: 10.1111/j.1600-0765.1997.tb00934.x PMID: 9401929Hortensius RA, Harley BAC. Naturally derived biomaterials for addressing inflammation in tissue regeneration. Exp Biol Med (Maywood) 2016; 241(10): 1015-24. doi: 10.1177/1535370216648022 PMID: 27190254Noguchi K, Ishikawa I. The roles of cyclooxygenase-2 and prostaglandin E 2 in periodontal disease. Periodontol 2000 2007; 43(1): 85-101. doi: 10.1111/j.1600-0757.2006.00170.x PMID: 17214837Yar M, Farooq A, Shahzadi L, et al. Novel meloxicam releasing electrospun polymer/ceramic reinforced biodegradable membranes for periodontal regeneration applications. Mater Sci Eng C 2016; 64: 148-56. doi: 10.1016/j.msec.2016.03.072 PMID: 27127039Van Dyke TE, Hasturk H, Kantarci A, et al. Proresolving nanomedicines activate bone regeneration in periodontitis. J Dent Res 2015; 94(1): 148-56. doi: 10.1177/0022034514557331 PMID: 25389003Zupancic S, Kocbek P, Baumgartner S, Kristl J. Contribution of nanotechnology to improved treatment of periodontal disease. Curr Pharm Des 2015; 21(22): 3257-71. doi: 10.2174/1381612821666150531171829 PMID: 26027560Cantón I, Mckean R, Charnley M, et al. Development of an Ibuprofen-releasing biodegradable PLA/PGA electrospun scaffold for tissue regeneration. Biotechnol Bioeng 2010; 105(2): 396-408. doi: 10.1002/bit.22530 PMID: 19731254Kasaj A, Reichert C, Götz H, Röhrig B, Smeets R, Willershausen B. In vitro evaluation of various bioabsorbable and nonresorbable barrier membranes for guided tissue regeneration. Head Face Med 2008; 4(1): 22. doi: 10.1186/1746-160X-4-22 PMID: 18854011Larjava H, Koivisto L, Häkkinen L, Heino J. Epithelial integrins with special reference to oral epithelia. J Dent Res 2011; 90(12): 1367-76. doi: 10.1177/0022034511402207 PMID: 21441220Gräber HG, Conrads G, Wilharm J, Lampert F. Role of interactions between integrins and extracellular matrix components in healthy epithelial tissue and establishment of a long junctional epithelium during periodontal wound healing: a review. J Periodontol 1999; 70(12): 1511-22. doi: 10.1902/jop.1999.70.12.1511 PMID: 10632527Preeja C, Janam P, Nayar BR. Fibrin clot adhesion to root surface treated with tetracycline hydrochloride and ethylenediaminetetraacetic acid: A scanning electron microscopic study. Dent Res J (Isfahan) 2013; 10(3): 382-8. PMID: 24019809Fairweather M, Heit YI, Buie J, et al. Celecoxib inhibits early cutaneous wound healing. J Surg Res 2015; 194(2): 717-24. doi: 10.1016/j.jss.2014.12.026 PMID: 25588948Zhang W, Ullah I, Shi L, et al. Fabrication and characterization of porous polycaprolactone scaffold via extrusion-based cryogenic 3D printing for tissue engineering. Mater Des 2019; 180: 107946. doi: 10.1016/j.matdes.2019.107946Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: state of the art and future trends. Macromol Biosci 2004; 4(8): 743-65. doi: 10.1002/mabi.200400026 PMID: 15468269Velasco MA, Narváez-Tovar CA, Garzón-Alvarado DA. Design, materials, and mechanobiology of biodegradable scaffolds for bone tissue engineering. BioMed Res Int 2015; 2015: 1-21. doi: 10.1155/2015/729076 PMID: 25883972Bose S, Roy M, Bandyopadhyay A. Recent advances in bone tissue engineering scaffolds. Trends Biotechnol 2012; 30(10): 546-54. doi: 10.1016/j.tibtech.2012.07.005 PMID: 22939815Burg KJL, Porter S, Kellam JF. Biomaterial developments for bone tissue engineering. Biomaterials 2000; 21(23): 2347-59. doi: 10.1016/S0142-9612(00)00102-2 PMID: 11055282Wei G, Ma PX. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. Biomaterials 2004; 25(19): 4749-57. doi: 10.1016/j.biomaterials.2003.12.005 PMID: 15120521Abbasi N, Ivanovski S, Gulati K, Love RM, Hamlet S. Role of offset and gradient architectures of 3-D melt electrowritten scaffold on differentiation and mineralization of osteoblasts. Biomater Res 2020; 24(1): 2. doi: 10.1186/s40824-019-0180-z PMID: 31911842Xie C, Gao Q, Wang P, et al. Structure-induced cell growth by 3D printing of heterogeneous scaffolds with ultrafine fibers. Mater Des 2019; 181: 108092. doi: 10.1016/j.matdes.2019.108092Fuchs A, Youssef A, Seher A, et al. Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration-a pilot study in vitro. BMC Oral Health 2019; 19(1): 28. doi: 10.1186/s12903-019-0717-5 PMID: 30709394Fuchs A, Youssef A, Seher A, et al. A new multilayered membrane for tissue engineering of oral hard- and soft tissue by means of melt electrospinning writing and film casting – An in vitro study. J Craniomaxillofac Surg 2019; 47(4): 695-703. doi: 10.1016/j.jcms.2019.01.043 PMID: 30826113Babaie E, Bhaduri SB. Fabrication aspects of porous biomaterials in orthopedic applications: A review. ACS Biomater Sci Eng 2018; 4(1): 1-39. doi: 10.1021/acsbiomaterials.7b00615 PMID: 33418675Porta M, Tonda-Turo C, Pierantozzi D, Ciardelli G, Mancuso E. Towards 3D multi-layer scaffolds for periodontal tissue engineering applications: Addressing manufacturing and architectural challenges. Polymers (Basel) 2020; 12(10): 2233. doi: 10.3390/polym12102233 PMID: 32998365Meifeng Zhu M, Li W, Dong X, et al. In vivo engineered extracellular matrix scaffolds with instructive niches for oriented tissue regeneration. Nat Commun 2019; 10(1): 1-14. PMID: 30602773Yamada S, Murakami S, Matoba R, et al. Expression profile of active genes in human periodontal ligament and isolation of PLAP-1, a novel SLRP family gene. Gene 2001; 275(2): 279-86. doi: 10.1016/S0378-1119(01)00683-7 PMID: 11587855Yamada S, Tomoeda M, Ozawa Y, et al. PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization. J Biol Chem 2007; 282(32): 23070-80. doi: 10.1074/jbc.M611181200 PMID: 17522060Ueda M, Goto T, Kuroishi KN, et al. Asporin in compressed periodontal ligament cells inhibits bone formation. Arch Oral Biol 2016; 62: 86-92. doi: 10.1016/j.archoralbio.2015.11.010 PMID: 26655952Horiuchi K, Amizuka N, Takeshita S, et al. Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor β. J Bone Miner Res 1999; 14(7): 1239-49. doi: 10.1359/jbmr.1999.14.7.1239 PMID: 10404027Kii I, Ito H. Periostin and its interacting proteins in the construction of extracellular architectures. Cell Mol Life Sci 2017; 74(23): 4269-77. doi: 10.1007/s00018-017-2644-4 PMID: 28887577Rios H, Koushik SV, Wang H, et al. periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype. Mol Cell Biol 2005; 25(24): 11131-44. doi: 10.1128/MCB.25.24.11131-11144.2005 PMID: 16314533Ríos HF, Ma D, Xie Y, et al. Periostin is essential for the integrity and function of the periodontal ligament during occlusal loading in mice. J Periodontol 2008; 79(8): 1480-90. doi: 10.1902/jop.2008.070624 PMID: 18672999Osorio R, Alfonso-Rodríguez CA, Osorio E, et al. Novel potential scaffold for periodontal tissue engineering. Clin Oral Investig 2017; 21(9): 2695-707. doi: 10.1007/s00784-017-2072-8 PMID: 28214952Sukpaita T, Chirachanchai S, Suwattanachai P, Everts V, Pimkhaokham A, Ampornaramveth RS. In vivo bone regeneration induced by a scaffold of chitosan/dicarboxylic acid seeded with human periodontal ligament cells. Int J Mol Sci 2019; 20(19): 4883. doi: 10.3390/ijms20194883 PMID: 31581495Basu A, Rothermund K, Ahmed MN, Syed-Picard FN. Self-assembly of an organized cementum-periodontal ligament-like complex using scaffold-free tissue engineering. Front Physiol 2019; 10: 422. doi: 10.3389/fphys.2019.00422 PMID: 31031642Batool F, Morand DN, Thomas L, et al. Synthesis of a novel electrospun polycaprolactone scaffold functionalized with ibuprofen for periodontal regeneration: An in vitro and in vivo study. Materials (Basel) 2018; 11(4): 580. doi: 10.3390/ma11040580 PMID: 29642582Ansari S, Diniz IM, Chen C, et al. Human periodontal ligament‐and gingiva‐derived mesenchymal stem cells promote nerve regeneration when encapsulated in alginate/hyaluronic acid 3D scaffold. Adv Healthc Mater 2017; 6(24): 1700670. doi: 10.1002/adhm.201700670 PMID: 29076281