Advertisement
Regenerative Endodontics|Articles in Press

Bone Regeneration Effect of Nanochitosan with or without Temporally Controlled Release of Dexamethasone

Published:March 08, 2023DOI:https://doi.org/10.1016/j.joen.2023.03.001

      Abstract

      Introduction

      Chitosan is a cationic biopolymer, and its modification as a nanoparticle as well as loading a corticosteroid on it may enhance its bone regenerative effect. The aim of this study was to investigate the bone regenerative effect of nanochitosan with or without dexamethasone.

      Methods

      Under general anesthesia, 4 cavities were created in the calvarium of 18 rabbits and filled with nanochitosan, nanochitosan with a temporally controlled release of dexamethasone (nanochitosan + dexamethasone), an autograft, or left unfilled (control). The defects were then covered with a collagen membrane. The rabbits were randomly divided into 2 groups and were sacrificed at 6 or 12 weeks after surgery. The new bone type, osteogenesis pattern, foreign body reaction, and the type and severity of the inflammatory response were evaluated histologically. The amount of new bone was determined using histomorphometry and cone-beam computed tomographic imaging. One-way analysis of variance with repeated measures was performed to compare results between the groups at each interval. A t test and chi-square test were also conducted to analyze changes in variables between the 2 intervals.

      Results

      Nanochitosan and the combination of nanochitosan and dexamethasone significantly increased the combination of woven and lamellar bone (P = .007). No sample showed a foreign body reaction or any acute or severe inflammation. Chronic inflammation was significantly decreased in number (P = .002) and severity (P = .003) over time. There was no significant difference between the extent and pattern of osteogenesis among the 4 groups, as evaluated by histomorphometry and cone-beam computed tomographic imaging at each interval.

      Conclusion

      Nanochitosan and nanochitosan + dexamethasone were comparable with the gold standard of autograft regarding the type and severity of inflammation as well as the level and pattern of osteogenesis; yet, they induced more woven and lamellar bone.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Endodontics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Sadeghi R.
        • Najafi M.
        • Semyari H.
        • Mashhadiabbas F.
        Histologic and histomorphometric evaluation of bone regeneration using nanocrystalline hydroxyapatite and human freeze-dried bone graft: An experimental study in rabbit.
        J Orofac Orthop. 2017; 78: 144-152
        • Yun P.Y.
        • Kim Y.K.
        • Jeong K.I.
        • et al.
        Influence of bone morphogenetic protein and proportion of hydroxyapatite on new bone formation in biphasic calcium phosphate graft: Two pilot studies in animal bony defect model.
        J Craniomaxillofac Surg. 2014; 42: 1909-1917
        • Younger E.M.
        • Chapman M.W.
        Morbidity at bone graft donor sites.
        J Orthop Trauma. 1989; 3: 192-195
        • Ezoddini-Ardakani F.
        • Navabazam A.
        • Fatehi F.
        • et al.
        Histologic evaluation of chitosan as an accelerator of bone regeneration in microdrilled rat tibias.
        Dent Res J (Isfahan). 2012; 9: 694-699
        • Kruse A.
        • Jung R.E.
        • Nicholls F.
        • et al.
        Bone regeneration in the presence of a synthetic hydroxyapatite/silica oxide-based and a xenogenic hydroxyapatite-based bone substitute material.
        Clin Oral Implants Res. 2011; 22: 506-511
        • Muzzarelli R.A.
        • Isolati A.
        • Ferrero A.
        Chitosan membranes.
        Ion Exch Membr. 1974; 1: 193-196
        • Rabea E.I.
        • Badawy M.E.
        • Stevens C.V.
        • et al.
        Chitosan as antimicrobial agent: Applications and mode of action.
        Biomacromolecules. 2003; 4: 1457-1465
        • Tan W.
        • Krishnaraj R.
        • Desai T.A.
        Evaluation of nanostructured composite collagen–chitosan matrices for tissue engineering.
        Tissue Eng. 2001; 7: 203-210
        • Agnihotri S.A.
        • Mallikarjuna N.N.
        • Aminabhavi T.M.
        Recent advances on chitosan-based micro- and nanoparticles in drug delivery.
        J Control Release. 2004; 100: 5-28
        • Shrestha S.
        • Diogenes A.
        • Kishen A.
        Temporal-controlled dexamethasone releasing chitosan nanoparticle system enhances odontogenic differentiation of stem cells from apical papilla.
        J Endod. 2015; 41: 1253-1258
        • Chevrier A.
        • Hoemann C.D.
        • Sun J.
        • Buschmann M.D.
        Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient vascularization and subchondral bone remodeling in drilled cartilage defects.
        Osteoarthritis Cartilage. 2007; 15: 316-327
        • Machida Y.
        • Nagai T.
        • Abe M.
        • Sannan T.
        Use of chitosan and hydroxypropylchitosan in drug formulations to effect sustained release.
        Drug Des Deliv. 1986; 1: 119-130
        • Bernkop-Schnürch A.
        Chitosan and its derivatives: Potential excipients for peroral peptide delivery systems.
        Int J Pharm. 2000; 194: 1-13
        • Kim I.Y.
        • Seo S.J.
        • Moon H.S.
        • et al.
        Chitosan and its derivatives for tissue engineering applications.
        Biotechnol Adv. 2008; 26: 1-21
        • Shrestha A.
        • Kishen A.
        Antibacterial nanoparticles in endodontics: a review.
        J Endod. 2016; 42: 1417-1426
        • Kishen A.
        • Shi Z.
        • Shrestha A.
        • Neoh K.G.
        An investigation on the antibacterial and antibiofilm efficacy of cationic nanoparticulates for root canal disinfection.
        J Endod. 2008; 34: 1515-1520
        • Bonnett R.
        • Krysteva M.A.
        • Lalov I.G.
        • Artarsky S.V.
        Water disinfection using photosensitizers immobilized on chitosan.
        Water Res. 2006; 40: 1269-1275
        • Wang X.H.
        • Li D.P.
        • Wang W.J.
        • et al.
        Crosslinked collagen/chitosan matrix for artificial livers.
        Biomaterials. 2003; 24: 3213-3220
        • Bellamy C.
        • Shrestha S.
        • Torneck C.
        • Kishen A.
        Effects of a bioactive scaffold containing a sustained transforming growth factor-β1-releasing nanoparticle system on the migration and differentiation of stem cells from the apical papilla.
        J Endod. 2016; 42: 1385-1392
        • Huang G.T.
        • Shagramanova K.
        • Chan S.W.
        Formation of odontoblast-like cells from cultured human dental pulp cells on dentin in vitro.
        J Endod. 2006; 32: 1066-1073
        • Nancy A.
        Ten Cate's Oral Histology. Development, Structure, and Function.
        9th ed. 2016
        • White S.C.
        • Rudolph D.J.
        Alterations of the trabecular pattern of the jaws in patients with osteoporosis.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999; 88: 628-635
        • Haddad A.J.
        • Peel S.A.
        • Clokie C.M.
        • Sándor G.K.
        Closure of rabbit calvarial critical-sized defects using protective composite allogeneic and alloplastic bone substitutes.
        J Craniofac Surg. 2006; 17: 926-934
        • Torres J.
        • Tamimi F.M.
        • Tresguerres I.F.
        • et al.
        Effect of solely applied platelet-rich plasma on osseous regeneration compared to Bio-Oss: A morphometric and densitometric study on rabbit calvaria.
        Clin Implant Dent Relat Res. 2008; 10: 106-112
        • Borie E.
        • Fuentes R.
        • Del Sol M.
        • et al.
        The influence of FDBA and autogenous bone particles on regeneration of calvaria defects in the rabbit: A pilot study.
        Ann Anat. 2011; 193: 412-417
        • Sohn J.Y.
        • Park J.C.
        • Um Y.J.
        • et al.
        Spontaneous healing capacity of rabbit cranial defects of various sizes.
        J Periodontal Implant Sci. 2010; 40: 180-187
        • Tamimi F.M.
        • Torres J.
        • Tresguerres I.
        • et al.
        Bone augmentation in rabbit calvariae: Comparative study between Bio-Oss and a novel beta-TCP/DCPD granulate.
        J Clin Periodontol. 2006; 33: 922-928
        • Herron S.
        • Thordarson D.B.
        • Winet H.
        • et al.
        Ingrowth of bone into absorbable bone cement: An in vivo microscopic evaluation.
        Am J Orthop (Belle Mead NJ). 2003; 32: 581-584
        • Boo J.S.
        • Yamada Y.
        • Okazaki Y.
        • et al.
        Tissue-engineered bone using mesenchymal stem cells and a biodegradable scaffold.
        J Craniofac Surg. 2002; 13: 231-239
        • Behfarnia P.
        • Shahabooei M.
        • Mashhadiabbas F.
        • Fakhari E.
        Comparison of bone regeneration using three demineralized freeze-dried bone allografts: A histological and histomorphometric study in rabbit calvaria.
        Dent Res J (Isfahan). 2012; 9: 554-560
        • Lee D.W.
        • Koo K.T.
        • Seol Y.J.
        • et al.
        Bone regeneration effects of human allogenous bone substitutes: A preliminary study.
        J Periodontal Implant Sci. 2010; 40: 132-138
        • Maruyama M.
        • Rhee C.
        • Utsunomiya T.
        • et al.
        Modulation of the inflammatory response and bone healing.
        Front Endocrinol (Lausanne). 2020; 11: 386
        • Hernandez C.J.
        • Majeska R.J.
        • Schaffler M.B.
        Osteocyte density in woven bone.
        Bone. 2004; 35: 1095-1099
        • Newman H.
        • Shih Y.V.
        • Varghese S.
        Resolution of inflammation in bone regeneration: From understandings to therapeutic applications.
        Biomaterials. 2021; 277: 121114
        • Thanou M.
        • Verhoef J.C.
        • Junginger H.E.
        Chitosan and its derivatives as intestinal absorption enhancers.
        Adv Drug Deliv Rev. 2001; 50: S91-S101
        • Rokn A.
        • Moslemi N.
        • Eslami B.
        • et al.
        Histologic evaluation of bone healing following application of anorganic bovine bone and β-tricalcium phosphate in rabbit calvaria.
        J Dent (Tehran). 2012; 9: 35-40