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Application of Chitosan in Bone and Dental Engineering

Alicia Aguilar, Naimah Zein, Ezeddine Harmouch and 8 more

Molecules · 2019 · Review · CC BY

doi:10.3390/molecules24163009

Abstract

Chitosan is a deacetylated polysaccharide from chitin, the natural biopolymer primarily found in shells of marine crustaceans and fungi cell walls. Upon deacetylation, the protonation of free amino groups of the d-glucosamine residues of chitosan turns it into a polycation, which can easily interact with DNA, proteins, lipids, or negatively charged synthetic polymers. This positive-charged characteristic of chitosan not only increases its solubility, biodegradability, and biocompatibility, but also directly contributes to the muco-adhesion, hemostasis, and antimicrobial properties of chitosan. Combined with its low-cost and economic nature, chitosan has been extensively studied and widely used in biopharmaceutical and biomedical applications for several decades. In this review, we summarize the current chitosan-based applications for bone and dental engineering. Combining chitosan-based scaffolds with other nature or synthetic polymers and biomaterials induces their mechanical properties and bioactivities, as well as promoting osteogenesis. Incorporating the bioactive molecules into these biocomposite scaffolds accelerates new bone regeneration and enhances neovascularization in vivo.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 22, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

The first bioerodable artificial polymer-cell scaffold was implanted into animals 30 years ago. Since then, tissue engineering has become an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue structure and function. Several biomaterials have been used for the fabrication of the scaffolds, including natural materials derived from animals or plants (collagen, starch, gelatin, alginate, cellulose, fibrin, hyaluronan, and chitosan) and synthetic materials, such as bioactive ceramics and a wide range of synthetic polymers. However, the excellent bio-based 3-dimentional (3D) polymer scaffolds should not only be non-toxic, biocompatible, and biodegradable, but also be competent in promoting cell adhesion and retaining the metabolic functions of attached cells, as the 3D polymer scaffolds used in tissue engineering should mimic and provide an actual in vivo surrounding microenvironment for the incorporation of cells or growth factors to regenerate damaged tissues or organs. The immunomodulatory biological effects of chitosan-based scaffold have also been described. In this regard, chitosan becomes one of the most commonly studied polymers in the scientific research, not only for biopharmaceutical and biomedical applications, but also for food science and technology.

2.1. Chitosan

Chitosan (CS) is a linear, semi-crystalline polysaccharide composed of β-(1→4)-2-acetamido-2-deoxy-b-d-glucan (n-acetyl d-glucosamine) and β-(1→4)-2-amino-2-deoxyb-d-glucan (d-glucosamine) units. Its molecular weight ranges from 10 to over 1000 kDa. Chitosan is not extensively present in the environment, however, it can be easily produced via the alkaline n-deacetylation process of the natural biopolymer commonly found in the shells of marine crustaceans and in fungi cells walls—the chitin (Figure 1). The deacetylation degree (DD) of chitosan, which gives an indication of the number of amino groups along the chains, is calculated as the ratio of d-glucosamine to the sum of d-glucosamine and n-acetyl d-glucosamine.

Chitin is a white, hard, inelastic, nitrogeneous polysaccharide. It is hydrophobic and is not soluble in water and most organic solvents, except for hexafluroisopropanol, hexafluroacetone, and chloroalcohols. This poor solubility of chitin is an extreme limit for its practical applications. However, the free amino groups of the d-glucosamine residues of chitosan, which could be protonated, provide a better solubility for chitosan by forming a non-Newtonian, shear-thinning fluid in most diluted acidic solutions at a pH below 6.5 (pKa value ~6.3) (Figure 1). With protonated amino groups, chitosan becomes a polycation and could subsequently form ionic complexes with a wide variety of natural or synthetic anionic species, for example, DNA, proteins, lipids, or negatively charged synthetic polymers such as poly(acrylic acid).

Chitosan can be biodegraded into non-toxic residues by lysozyme or chitinase, which hydrolyses glucosamine-glucosamine, glucosamine-n-acetyl-glucosamine, and n-acetyl-glucosamine-n-acetyl-glucosamine linkages. The rate and extent of chitosan’s biodegradability in living organisms are highly related to the molecular mass of the polymer and its deacetylation degree (DD). The chitosan DD can also influence its biocompatibility. A higher DD increases the number of positive charges which increases the interaction between chitosan and cells, leading to an improved biocompatibility. In addition, chitosan is a low-cost and economic natural biopolymer. The price of chitin (3.6–6.0 US$/kg)/chitosan (30–500 US$/kg) are hundreds or thousands of times higher than the price of shell wastes (0.05–0.15 US$/kg), while the production costs were around 1.70 US$/kg for chitin and 3.50 US$/kg for chitosan 40 years ago.

2.2. Medical and Pharmaceutical Properties of Chitosan

As a natural multifunctional polysaccharide, chitosan has been widely studied for biomedical, surgical, and tissue engineering and pharmaceutical application, thanks to its biocompatibility, biodegradability, and muco-adhesiveness. Chitosan is reported to be increasingly used in the United States as an over-the-counter cholesterol-lowering agent. Positively-charged deacetylated chitosan could bind negatively charged molecules, such as fatty acids, lipids, and bile acids, in the intestinal tract, excreting these molecules from the body. Chitosan is thus considered as a promising candidate for obesity and hypercholesterolemia treatment. Chitosan could be also used for wastewater treatment and beverage clarification because of its good chelating or binding capacity of protonable amino groups for various species, such as metal ions. However, the most important medical and pharmaceutical applications of chitosan are drug delivery, wound dressings, and biocomposite scaffolds for tissue engineering.

2.2.1. Drug Delivery

The positively charged protonable amino group of the d-glucosamine residues of chitosan can interact with the negatively charged sialic acid residues of the glycoprotein which composes the mucus. Thus, the muco-adhesion is directly related to the DD of chitosan, with higher chitosan DD resulting in increased positive charges which enhance its muco-adhesive properties. It has also been reported that chitosan can interact with the negative part of the cell membrane, enhancing the penetration of an active agent through the epithelium layer that contains tight junctions. Consequently, owing to the muco-adhesion and enhanced penetration properties, chitosan is a suitable excipient to prepare oral, nasal, ocular, vaginal, and subcutaneous delivery forms and be used as a vaccine adjuvant or co-adjuvant to enhance the bioavailability and immunogenicity of antigens.

2.2.2. Wound Dressings

Wound healing is a particular biological phenomenon, which progresses through a series of inter-reliant and corresponding stages to regenerate the integrity of damaged tissue and replacement of lost tissue. The hemostatic and antimicrobial properties of chitosan enable its application in wound dressings.

Again, as a natural positive-charged polysaccharide, protonable amino groups on the chitosan backbone electrostatically interact with the various negatively charged proteins and glycolipids on the surface of red blood cells (RBC). This interaction increases blood viscosity, activates platelet adhesion and aggregation, and enhances the transportation of platelets to the vascular wall for physiological hemostasis. Blood clots are formed by intensive aggregation of RBC around the wound site to quickly stop bleeding. Thus, the number of positive charged amino groups on chitosan directly plays an important role in its hemostatic property.

The antimicrobial activity of chitosan has been demonstrated against different microorganisms both in vivo and in vitro, such as bacteria (either Gram-positive or Gram-negative), yeast, fungi, and algae, which makes chitosan a good candidate as an antimicrobial agent in solution, film, and composite. This antimicrobial property of chitosan has been related to the presence of its cationic nature. However, this antimicrobial activity could also depend on other intrinsic factors (for example, the type of chitosan or the degree of chitosan polymerization and deacetylation) and extrinsic factors (such as the live host, the microorganisms, and the environmental conditions). Until now, the antimicrobial activity of chitosan has not yet been fully understood.

2.3. Chitosan-Based Scaffold Preparation

The most common method to generate chitosan scaffolds is by freezing and lyophilizing chitosan solution. The spaces occupied by ice crystals formed in frozen chitosan solution are emptied during the sublimation, leading to the formation of pores. However, a precise control of temperature is required to form good pore structures. Another method to form porous scaffolds is called salt leaching. Salt crystals such as NaCl are used as porogens and put into a mold, and chitosan is then poured over the salt, penetrating into all the small spaces left between the salt crystals. The mold is then heated to melt the chitosan powder in an oven for a sufficient time. The chilled chitosan/NaCl mixture is then separated from the mold and the salt is washed away by water or alcohol, generating open pores in the chitosan scaffolds. In addition, fibrous chitosan scaffolds are formed by electrospinning. An applied electric field causes the elongation of the chitosan drop and leads to the formation of long fibers ranging from the submicron level to several nanometers in diameter.

Besides the dried chitosan-based scaffold preparation discussed above, chitosan-based scaffolds could also be prepared as hydrogels. A hydrogel is a network of the same or different types of cross-linked polymer chains with good water absorption capacity. Chemically cross-linked hydrogels are formed by covalent linking of chitosan macromers, in which the bond formation is irreversible. Covalent cross-linking can also be formed between polymers and a cross-linker, or via photopolymerization. Another way to prepare chitosan-based hydrogel is by physical cross-linking through ionic interactions. Polyelectrolyte complex networks are formed via ionic interactions between positively charged chitosan and anions or other negatively charged polymers. Although chemically cross-linked chitosan-based hydrogels show better stability and resistance to environmental variables, physically cross-linked hydrogels are more biocompatible because of the lack of chemical cross-linkers.

2.4. Chitosan-Based Scaffolds for Bone Regeneration

Bone is a hard and highly functionalized connective tissue constituting the skeletal framework of the human body. It supports fleshy structures, protects vital organs, and is involved in various physiological functions such as the maintenance of phosphocalcic homeostasis. After an injury, if the impairment is mild and the defect size is small, bone tissue has certain self-healing potential through osteogenic differentiation of bone marrow mesenchymal stem cells, bone neoformation, and neo-angiogenesis at the lesion site. For large-size bone defects, bone grafts are usually needed, however, these clinical procedures have many disadvantages.

In the context of bone engineering, the physiological inertness and low toxic effects of chitosan-based scaffolds have been demonstrated by numerous in vitro and in vivo studies (Table 1). In addition, no allergic and inflammatory reactions upon chitosan-based material implantation, injection, or topical application in the human body have been proven; however, the use of chitosan as scaffold is limited by having reduced bioactivities and mechanical properties. This disadvantage has been overcome by mixing the chitosan scaffolds with other synthetic or natural polymers [poly(vinyl alcohol), poly-ɛ-caprolactone, alginate, collagen, silk fibroin, etc.], biomaterials (hydroxyapatite, β-tricalcium phosphate, SiO2, etc.), or bioactive pharmacological molecules (bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), bisphosphonate, etc.).

Indeed, blending chitosan with most of the aforementioned polymer and/or biomaterials efficiently reinforces its mechanical properties and improves its bioactivities, such as increased protein absorption and increased biomineralization (Table 1). However, many of the published biocomposite scaffolds could not decrease the biodegradation rate of chitosan, which affects their long-term in vivo persistence (Table 1). Water retention ability is another parameter important for tissue engineering scaffolds, as the increased water retention ability of scaffold implanted in vivo could lead to the loosening and dislocation of the implant. As summarized in Table 1, most of the biocomposite scaffolds reported controls and decreased their water retention ability.

Most importantly, both in vitro and in vivo experiments demonstrated that all these chitosan-based biocomposite scaffolds are not toxic, and have very good properties of biocompatibility, osteoconductivity, and osteogenesis, promoting good cell proliferation and cell adhesion, causing an increase in new bone regeneration. Regarding more specific clinical applications of chitosan in alveolar bone and jawbone regeneration, several preclinical reports showed promising results, even for accelerating dental implant osseointegration and reconstructing critical size defects.

Over the last decade, the functionality of these chitosan-based biocomposite scaffolds have been enhanced by incorporating bioactive molecules into drug delivery systems. Therefore, bioactive molecules could be locally delivered with an adequate dose for a desired period, avoiding the drug release to non-target sites. Bone morphogenetic proteins (BMPs) are a group of growth factors originally discovered by their ability to induce bone and cartilage formation. Transforming growth factor beta 1 (TGF-β1) is a polypeptide member of the transforming growth factor beta superfamily of cytokines, controlling cell growth, cell proliferation, and cell differentiation in many cell types. Studies have shown that chitosan-based biocomposite associated with either BMP2, BMP-7 or TGF-β1 efficiently induced osteogenesis and promoted a large amount new bone formation compared with control or sham groups (see Table 1). Vascular endothelial growth factor (VEGF) is a signal protein stimulating the formation of blood vessels. Incorporating VEGF into chitosan-based biocomposite scaffolds induces angiogenesis and enhances neovascularization in bone healing (see Table 1).

2.5. Chitosan-Based Application for Dental Engineering: The Case of Periodontal Regeneration

Periodontitis is a chronic inflammatory disease induced by bacterial infection, affecting tooth-supporting tissues and leading to significant destruction of the periodontium (i.e., gingiva, alveolar bone, periodontal ligament, cement). Such a disease is common in the global population (>50% in the U.S. population) and is the main cause of tooth loss. It is characterized by the development of the periodontal pocket and, in severe cases, of infrabony defects. Treatment of such lesions represent a challenge for the clinician. Indeed, periodontal treatment aims to reduce the inflammation and to control the infection by chemical (antibiotics, antiseptics) and mechanical treatments (scaling and root planing). However, such a treatment strategy is associated mainly to wound repair, characterized by a long junctional epithelium. In most severe cases (probing pocket depth (PPD) > 5 mm), non-surgical treatment alone could be insufficient in emphasizing the need of adjuvant therapy. Therefore, the use of local delivery of active drugs or compounds has been suggested to target inflammation and infection, and in promoting tissue regeneration. During the last decade, a specific interest was made towards the chitosan-based delivery system. Several chitosan-based devices have been designed and evaluated in specific contexts, including in micro/nanoparticles, fibers, membrane, and gels. Chitosan gels exhibit interesting physical properties that could be modulated by the concentration of chitosan. Indeed, it was shown that such chitosan-based gels (1–4%) have an interesting viscosity to be injected within periodontal pockets. Most importantly, they can be used as a reliable vehicle to release active drugs at the disease site. While a sustained release could be considered ideal, it is important to note that the kinetic of release is a parameter that is also influenced by the percentage of chitosan. Drugs, such as statins, doxycycline, or other antibiotics/antiseptics such as tetracyclines, have been incorporated in such devices.

Interestingly, adjuvant use of such drug-loaded scaffolds improved periodontal healing, emphasizing the interest in their use. For instance, Chang et al. evaluated in vivo, in an experimental periodontitis murine model, the use of a chitosan-based hydrogel loaded with naringin, a natural compound with anti-inflammatory properties. They demonstrated the interesting properties of chitosan hydrogel, as its injection at the lesion site was associated with a burst release of the active compound during the acute phase of the inflammation, inducing an anti-inflammatory effect within periodontal tissues. Such results might be explained by the controlled local delivery at the lesion site and the 3D characteristics of the chitosan scaffold.

Interestingly, it was also demonstrated that chitosan can potentialize the antibacterial effect of chlorhexidine, showing the intrinsic property of chitosan.

2.6. Chitosan-Based Scaffold in Dental-Pulp Regeneration

The endodontic space located in the heart of the tooth contains pulp, which is crucial for its vitality. This soft connective tissue contains collagen fibers, dental stem cells, vascularization, and innervation surrounded by dentin. This pulp-dentin complex is very reactive and, after significant aggression, the painful inflammatory reaction of the pulp–dentin complex is often hard to dissipate and leads to pulp necrosis. The conventional endodontic treatment is drastic, as all tissues are removed whatever their regenerative potentials. Recently, regenerative strategies targeting regeneration of pulp connective-tissue, dentin, radicular edification, vascularization, and innervation were developed. Scaffolds represent the key element of the endodontic treatment. They are essential for delivering active molecules and for carrying competent cells within the endodontic compartment. They must have an adequate viscosity, allowing their injection in the whole root canal system, and porosity, which is crucial for cell colonization.

Recently, chitosan-based scaffolds have been developed for this purpose. They are favorable, not only for pulp regeneration, but also for dentin formation because of their capacities to induce mineralization. Indeed, chitosan scaffolds containing β-tricalcium phosphate promoted a high expression of mineralization markers, such as osteopontin and alkaline phosphatase, and dentin formation by human periodontal ligament cells (HPLCs). In addition, several recent reports demonstrated that chitosan-based scaffolds promoted the proliferation, migration, and odontoblastic differentiation of dental pulp stem cells and mesenchymal stem cells both in vitro and in vivo (Table 2). The use of chitosan as a vector for antimicrobials has also been tested with interesting outcomes.

3. Conclusions

As a positive-charged, low-cost natural polymer with good biodegradability and biocompatibility, as well as having non-toxic, muco-adhesive, hemostatic, and antimicrobial properties, chitosan is a good candidate for biomedical and biopharmaceutical research. Consequently, chitosan-based scaffolds have been widely studied and applied in tissue engineering for the last two decades. Indeed, blending chitosan with other natural or synthetic polymers and/or biomaterials could efficiently control the porosity and water retention of these biocomposite scaffolds, reduce their biodegradation rate, enhance their bioactivity and biocompatibility, and increase their mechanical properties. Importantly, as demonstrated in both in vitro and in vivo studies, most of these biocomposite scaffolds have no cytotoxicity and promote the attachment and proliferation of cells for tissue repair. In addition, the combination of bioactive molecules with these chitosan-based biocomposite scaffolds could not only promote the proliferation and differentiation of stem cells and accelerate the tissue regeneration, but also induce angiogenesis and vascularization in different animal models, which could consequently be used in human clinical trials.

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    Lim J.I., Lee Y.-K., Shin J.-S., Lim K.-J. Preparation of interconnected porous chitosan scaffolds by sodium acetate particulate leaching. J. Biomater. Sci. Polym. Ed. 2011;22:1319-1329.

    Not in our library10.1163/092050610x504783

  50. 50.

    Pezeshki-Modaress M., Rajabi-Zeleti S., Zandi M., Mirzadeh H., Sodeifi N., Nekookar A., Aghdami N. Cell-loaded gelatin/chitosan scaffolds fabricated by salt-leaching/lyophilization for skin tissue engineering: In vitro and in vivo study. J. Biomed. Mater. Res. A. 2014;102:3908-3917.

    Not in our library10.1002/jbm.a.35054

  51. 51.

    Geng X., Kwon O.-H., Jang J. Electrospinning of chitosan dissolved in concentrated acetic acid solution. Biomaterials. 2005;26:5427-5432.

    Not in our library10.1016/j.biomaterials.2005.01.066

  52. 52.

    Dahlin R.L., Kasper F.K., Mikos A.G. Polymeric nanofibers in tissue engineering. Tissue Eng. Part. B Rev. 2011;17:349-364.

    Not in our library10.1089/ten.teb.2011.0238

  53. 53.

    Ahmadi F., Oveisi Z., Samani S.M., Amoozgar Z. Chitosan based hydrogels: Characteristics and pharmaceutical applications. Res. Pharm. Sci. 2015;10:1-16.

    Not in our library

  54. 54.

    Bhattarai N., Gunn J., Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv. Drug Deliv. Rev. 2010;62:83-99.

    Not in our library10.1016/j.addr.2009.07.019

  55. 55.

    Chen R., Chen Q., Huo D., Ding Y., Hu Y., Jiang X. In situ formation of chitosan-gold hybrid hydrogel and its application for drug delivery. Colloids Surf B Biointerfaces. 2012;97:132-137.

    Not in our library10.1016/j.colsurfb.2012.03.027

  56. 56.

    Walsh J.S. Normal bone physiology, remodelling and its hormonal regulation. Surg. (Oxf). 2015;33:1-6.

    Not in our library10.1016/j.mpsur.2014.10.010

  57. 57.

    Arvidson K., Abdallah B.M., Applegate L.A., Baldini N., Cenni E., Gomez-Barrena E., Granchi D., Kassem M., Konttinen Y.T., Mustafa K., et al. Bone regeneration and stem cells. J. Cell Mol. Med. 2011;15:718-746.

    Not in our library10.1111/j.1582-4934.2010.01224.x

  58. 58.

    Loi F., Córdova L.A., Pajarinen J., Lin T., Yao Z., Goodman S.B. Inflammation, fracture and bone repair. Bone. 2016;86:119-130.

    Not in our library10.1016/j.bone.2016.02.020

  59. 59.

    Gómez-Barrena E., Rosset P., Lozano D., Stanovici J., Ermthaller C., Gerbhard F. Bone fracture healing: Cell therapy in delayed unions and nonunions. Bone. 2015;70:93-101.

    Not in our library10.1016/j.bone.2014.07.033

  60. 60.

    Rogers G.F., Greene A.K. Autogenous bone graft: basic science and clinical implications. J. Craniofac. Surg. 2012;23:323-327.

    Not in our library10.1097/scs.0b013e318241dcba

  61. 61.

    Waibel K.H., Haney B., Moore M., Whisman B., Gomez R. Safety of chitosan bandages in shellfish allergic patients. Mil. Med. 2011;176:1153-1156.

    Not in our library10.7205/milmed-d-11-00150

  62. 62.

    Jiang T., Ji H., Zhang L., Wang Y., Zhou H. Chitosan Oligosaccharide Exerts Anti-Allergic Effect against Shrimp Tropomyosin-Induced Food Allergy by Affecting Th1 and Th2 Cytokines. Int. Arch. Allergy Immunol. 2019;1-7.

    Not in our library10.1159/000500720

  63. 63.
  64. 64.

    Bhattarai G., Lee Y.-H., Lee M.-H., Park I.-S., Yi H.-K. Insulin-like growth factor binding protein-3 affects osteogenic efficacy on dental implants in rat mandible. Mater. Sci. Eng. C Mater. Biol. Appl. 2015;55:490-496.

    Not in our library10.1016/j.msec.2015.05.076

  65. 65.

    Bhattarai G., Lee Y.H., Lee M.H., Yi H.K. Gene delivery of c-myb increases bone formation surrounding oral implants. J. Dent. Res. 2013;92:840-845.

    Not in our library10.1177/0022034513497753

  66. 66.

    Lee Y.-H., Kim J.-S., Kim J.-E., Lee M.-H., Jeon J.-G., Park I.-S., Yi H.-K. Nanoparticle mediated PPARγ gene delivery on dental implants improves osseointegration via mitochondrial biogenesis in diabetes mellitus rat model. Nanomedicine. 2017;13:1821-1832.

    Not in our library10.1016/j.nano.2017.02.020

  67. 67.

    Li H., Ji Q., Chen X., Sun Y., Xu Q., Deng P., Hu F., Yang J. Accelerated bony defect healing based on chitosan thermosensitive hydrogel scaffolds embedded with chitosan nanoparticles for the delivery of BMP2 plasmid DNA. J. Biomed. Mater. Res. A. 2017;105:265-273.

    Not in our library10.1002/jbm.a.35900

  68. 68.

    Bleuming S.A., He X.C., Kodach L.L., Hardwick J.C., Koopman F.A., ten Kate F.J., van Deventer S.J.H., Hommes D.W., Peppelenbosch M.P., Offerhaus G.J., et al. Bone Morphogenetic Protein Signaling Suppresses Tumorigenesis at Gastric Epithelial Transition Zones in Mice. Cancer Res. 2007;67:8149-8155.

    Not in our library10.1158/0008-5472.can-06-4659

  69. 69.

    Kinane D.F., Stathopoulou P.G., Papapanou P.N. Periodontal diseases. Nat. Rev. Dis. Primers. 2017;3:17038.

    Not in our library10.1038/nrdp.2017.38

  70. 70.

    Cortellini P., Tonetti M.S. Clinical concepts for regenerative therapy in intrabony defects. Periodontol. 2000. 2015;68:282-307.

    Not in our library10.1111/prd.12048

  71. 71.

    Cortellini P., Tonetti M.S. Focus on intrabony defects: Guided tissue regeneration. Periodontol. 2000. 2000;22:104-132.

    Not in our library10.1034/j.1600-0757.2000.2220108.x

  72. 72.

    Harmouche L., Courval A., Mathieu A., Petit C., Huck O., Severac F., Davideau J.-L. Impact of tooth-related factors on photodynamic therapy effectiveness during active periodontal therapy: A 6-months split-mouth randomized clinical trial. Photodiagnosis Photodyn. 2019;190-194.

    Not in our library10.1016/j.pdpdt.2019.05.022

  73. 73.

    Abdul Rahman N., Nickles K., Gallenbach K., Dannewitz B., Ramich T., Scharf S., Röllke L., Schacher B., Eickholz P. Five-year stability of clinical attachment after regenerative treatment of infrabony defects compared to controls. J. Clin. Periodontol. 2019;46:650-658.

    Not in our library10.1111/jcpe.13105

  74. 74.

    Da Rocha H.A.J., Silva C.F., Santiago F.L., Martins L.G., Dias P.C., De Magalhães D. Local Drug Delivery Systems in the Treatment of Periodontitis: A Literature Review. J. Int. Acad. Periodontol. 2015;17:82-90.

    Not in our library

  75. 75.

    Morand D.N., Davideau J.-L., Clauss F., Jessel N., Tenenbaum H., Huck O. Cytokines during periodontal wound healing: Potential application for new therapeutic approach. Oral Dis. 2017;23:300-311.

    Not in our library10.1111/odi.12469

  76. 76.
  77. 77.

    Petit C., Batool F., Bugueno I.M., Schwinté P., Benkirane-Jessel N., Huck O. Contribution of Statins towards Periodontal Treatment: A Review. Mediat. Inflamm. 2019;2019:6367402.

    Not in our library10.1155/2019/6367402

  78. 78.

    Sah A.K., Dewangan M., Suresh P.K. Potential of chitosan-based carrier for periodontal drug delivery. Colloids Surf. B: Biointerfaces. 2019;178:185-198.

    Not in our library10.1016/j.colsurfb.2019.02.044

  79. 79.

    Yar M., Farooq A., Shahzadi L., Khan A.S., Mahmood N., Rauf A., Chaudhry A.A., Rehman I.U. Novel meloxicam releasing electrospun polymer/ceramic reinforced biodegradable membranes for periodontal regeneration applications. Mater. Sci. Eng. C Mater. Biol. Appl. 2016;64:148-156.

    Not in our library10.1016/j.msec.2016.03.072

  80. 80.

    Kamal T., Khan S.B., Haider S., Alghamdi Y.G., Asiri A.M. Thin layer chitosan-coated cellulose filter paper as substrate for immobilization of catalytic cobalt nanoparticles. Int. J. Biol. Macromol. 2017;104:56-62.

    Not in our library10.1016/j.ijbiomac.2017.05.157

  81. 81.

    Işılay Özdoğan A., Akca G., Şenel S. Development and in vitro evaluation of chitosan based system for local delivery of atorvastatin for treatment of periodontitis. Eur. J. Pharm. Sci. 2018;124:208-216.

    Not in our library10.1016/j.ejps.2018.08.037

  82. 82.

    Ganguly A., Ian C.K., Sheshala R., Sahu P.S., Al-Waeli H., Meka V.S. Application of diverse natural polymers in the design of oral gels for the treatment of periodontal diseases. J. Mater. Sci. Mater. Med. 2017;28:39.

    Not in our library10.1007/s10856-017-5852-4

  83. 83.

    Özdoğan A.I., İlarslan Y.D., Kösemehmetoğlu K., Akca G., Kutlu H.B., Comerdov E., Iskit A.B., Şenel S. In vivo evaluation of chitosan based local delivery systems for atorvastatin in treatment of periodontitis. Int. J. Pharm. 2018;550:470-476.

    Not in our library10.1016/j.ijpharm.2018.08.058

  84. 84.

    Madi M., Pavlic V., Samy W., Alagl A. The anti-inflammatory effect of locally delivered nano-doxycycline gel in therapy of chronic periodontitis. Acta Odontol. Scand. 2018;76:71-76.

    Not in our library10.1080/00016357.2017.1385096

  85. 85.

    Khan G., Yadav S.K., Patel R.R., Nath G., Bansal M., Mishra B. Development and Evaluation of Biodegradable Chitosan Films of Metronidazole and Levofloxacin for the Management of Periodontitis. Aaps Pharmscitech. 2016;17:1312-1325.

    Not in our library10.1208/s12249-015-0466-y

  86. 86.

    Lin C.-Y., Tseng K.-S., Liu J.-M., Chuang H.-C., Lien C.-H., Chen Y.-C., Lai C.-Y., Yu C.-P., Hsu R.-J. Increased Risk of Ulcerative Colitis in Patients with Periodontal Disease: A Nationwide Population-Based Cohort Study. Int. J. Env. Res. Public Health. 2018;15:2602.

    Not in our library10.3390/ijerph15112602

  87. 87.

    Kilicarslan M., Gumustas M., Yildiz S., Baykara T. Preparation and characterization of chitosan-based spray-dried microparticles for the delivery of clindamycin phosphate to periodontal pockets. Curr. Drug Deliv. 2014;11:98-111.

    Not in our library10.2174/15672018113109990055

  88. 88.

    Chang P.-C., Chao Y.-C., Hsiao M.-H., Chou H.-S., Jheng Y.-H., Yu X.-H., Lee N., Yang C., Liu D.-M. Inhibition of Periodontitis Induction Using a Stimuli-Responsive Hydrogel Carrying Naringin. J. Periodontol. 2017;88:190-196.

    Not in our library10.1902/jop.2016.160189

  89. 89.

    Barreras U.S., Méndez F.T., Martínez R.E.M., Valencia C.S., Rodríguez P.R.M., Rodríguez J.P.L. Chitosan nanoparticles enhance the antibacterial activity of chlorhexidine in collagen membranes used for periapical guided tissue regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 2016;58:1182-1187.

    Not in our library10.1016/j.msec.2015.09.085

  90. 90.

    Ferrand A., Eap S., Richert L., Lemoine S., Kalaskar D., Demoustier-Champagne S., Atmani H., Mély Y., Fioretti F., Schlatter G., et al. Osteogenetic properties of electrospun nanofibrous PCL scaffolds equipped with chitosan-based nanoreservoirs of growth factors. Macromol. Biosci. 2014;14:45-55.

    Not in our library10.1002/mabi.201300283

  91. 91.

    Issa J.P.M., do Nascimento C., Bentley M.V.L.B., Del Bel E.A., Iyomasa M.M., Sebald W., de Albuquerque R.F. Bone repair in rat mandible by rhBMP-2 associated with two carriers. Micron. 2008;39:373-379.

    Not in our library10.1016/j.micron.2007.03.008

  92. 92.

    Seol Y.-J., Lee J.-Y., Park Y.-J., Lee Y.-M., Young-Ku N., Rhyu I.-C., Lee S.-J., Han S.-B., Chung C.-P. Chitosan sponges as tissue engineering scaffolds for bone formation. Biotechnol. Lett. 2004;26:1037-1041.

    Not in our library10.1023/b:bile.0000032962.79531.fd

  93. 93.

    Mohammadi R., Amini K. Guided bone regeneration of mandibles using chitosan scaffold seeded with characterized uncultured omental adipose-derived stromal vascular fraction: An animal study. Int. J. Oral Maxillofac Implant. 2015;30:216-222.

    Not in our library10.11607/jomi.3542

  94. 94.

    Xu F., Wu Y., Zhang Y., Yin P., Fang C., Wang J. Influence of in vitro differentiation status on the in vivo bone regeneration of cell/chitosan microspheres using a rat cranial defect model. J. Biomater. Sci. Polym. Ed. 2019;30:1008-1025.

    Not in our library10.1080/09205063.2019.1619959

  95. 95.

    Danilchenko S.N., Kalinkevich O.V., Pogorelov M.V., Kalinkevich A.N., Sklyar A.M., Kalinichenko T.G., Ilyashenko V.Y., Starikov V.V., Bumeyster V.I., Sikora V.Z., et al. Characterization and in vivo evaluation of chitosan-hydroxyapatite bone scaffolds made by one step coprecipitation method. J. Biomed. Mater. Res. Part. A. 2011;96A:639-647.

    Not in our library10.1002/jbm.a.33017

  96. 96.

    Zhang X., Zhu L., Lv H., Cao Y., Liu Y., Xu Y., Ye W., Wang J. Repair of rabbit femoral condyle bone defects with injectable nanohydroxyapatite/chitosan composites. J. Mater. Sci. Mater. Med. 2012;23:1941-1949.

    Not in our library10.1007/s10856-012-4662-y

  97. 97.

    Gaihre B., Jayasuriya A.C. Comparative investigation of porous nano-hydroxyapaptite/chitosan, nano-zirconia/chitosan and novel nano-calcium zirconate/chitosan composite scaffolds for their potential applications in bone regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 2018;91:330-339.

    Not in our library10.1016/j.msec.2018.05.060

  98. 98.

    Cho B.C., Chung H.Y., Lee D.G., Yang J.D., Park J.W., Roh K.H., Kim G.U., Lee D.S., Kwon I.C., Bae E.H., et al. The effect of chitosan bead encapsulating calcium sulfate as an injectable bone substitute on consolidation in the mandibular distraction osteogenesis of a dog model. J. Oral Maxillofac. Surg. 2005;63:1753-1764.

    Not in our library10.1016/j.joms.2004.10.011

  99. 99.

    Pattnaik S., Nethala S., Tripathi A., Saravanan S., Moorthi A., Selvamurugan N. Chitosan scaffolds containing silicon dioxide and zirconia nano particles for bone tissue engineering. Int. J. Biol. Macromol. 2011;49:1167-1172.

    Not in our library10.1016/j.ijbiomac.2011.09.016

  100. 100.

    Shokri S., Movahedi B., Rafieinia M., Salehi H. A new approach to fabrication of Cs/BG/CNT nanocomposite scaffold towards bone tissue engineering and evaluation of its properties. Appl. Surf. Sci. 2015;357:1758-1764.

    Not in our library10.1016/j.apsusc.2015.10.048

  101. 101.

    Kucharska M., Butruk B., Walenko K., Brynk T., Ciach T. Fabrication of in-situ foamed chitosan/β-TCP scaffolds for bone tissue engineering application. Mater. Lett. 2012;85:124-127.

    Not in our library10.1016/j.matlet.2012.07.002

  102. 102.

    Cheng G., Li Z., Wan Q., Lv K., Li D., Xing X., Li Z. A novel animal model treated with tooth extraction to repair the full-thickness defects in the mandible of rabbits. J. Surg. Res. 2015;194:706-716.

    Not in our library10.1016/j.jss.2014.11.010

  103. 103.

    Chang H.-H., Wang Y.-L., Chiang Y.-C., Chen Y.-L., Chuang Y.-H., Tsai S.-J., Heish K.-H., Lin F.-H., Lin C.-P. A Novel Chitosan-γPGA Polyelectrolyte Complex Hydrogel Promotes Early New Bone Formation in the Alveolar Socket Following Tooth Extraction. PloS ONE. 2014;9:e92362.

    Not in our library10.1371/journal.pone.0092362

  104. 104.

    Fan J., Park H., Lee M.K., Bezouglaia O., Fartash A., Kim J., Aghaloo T., Lee M. Adipose-derived stem cells and BMP-2 delivery in chitosan-based 3D constructs to enhance bone regeneration in a rat mandibular defect model. Tissue Eng. Part. A. 2014;20:2169-2179.

    Not in our library10.1089/ten.tea.2013.0523

  105. 105.

    Pourhaghgouy M., Zamanian A., Shahrezaee M., Masouleh M.P. Physicochemical properties and bioactivity of freeze-cast chitosan nanocomposite scaffolds reinforced with bioactive glass. Mater. Sci. Eng. C Mater. Biol. Appl. 2016;58:180-186.

    Not in our library10.1016/j.msec.2015.07.065

  106. 106.

    Nazemi K., Azadpour P., Moztarzadeh F., Urbanska A.M., Mozafari M. Tissue-engineered chitosan/bioactive glass bone scaffolds integrated with PLGA nanoparticles: A therapeutic design for on-demand drug delivery. Mater. Lett. 2015;138:16-20.

    Not in our library10.1016/j.matlet.2014.09.086

  107. 107.

    Venkatesan J., Ryu B., Sudha P.N., Kim S.-K. Preparation and characterization of chitosan–carbon nanotube scaffolds for bone tissue engineering. Int. J. Biol. Macromol. 2012;50:393-402.

    Not in our library10.1016/j.ijbiomac.2011.12.032

  108. 108.

    Saravanan S., Sameera D.K., Moorthi A., Selvamurugan N. Chitosan scaffolds containing chicken feather keratin nanoparticles for bone tissue engineering. Int. J. Biol. Macromol. 2013;62:481-486.

    Not in our library10.1016/j.ijbiomac.2013.09.034

  109. 109.

    Maglione M., Spano S., Ruaro M.E., Salvador E., Zanconati F., Tromba G., Turco G. In vivo evaluation of chitosan-glycerol gel scaffolds seeded with stem cells for full-thickness mandibular bone regeneration. J. Oral Sci. 2017;59:225-232.

    Not in our library10.2334/josnusd.16-0235

  110. 110.

    Saravanan S., Vimalraj S., Anuradha D. Chitosan based thermoresponsive hydrogel containing graphene oxide for bone tissue repair. Biomed. Pharm. 2018;107:908-917.

    Not in our library10.1016/j.biopha.2018.08.072

  111. 111.
  112. 112.

    Jayakumar R., Ramachandran R., Sudheesh Kumar P.T., Divyarani V.V., Srinivasan S., Chennazhi K.P., Tamura H., Nair S.V. Fabrication of chitin–chitosan/nano ZrO2 composite scaffolds for tissue engineering applications. Int. J. Biol. Macromol. 2011;49:274-280.

    Not in our library10.1016/j.ijbiomac.2011.04.020

  113. 113.

    Park J.-S., Choi S.-H., Moon I.-S., Cho K.-S., Chai J.-K., Kim C.-K. Eight-week histological analysis on the effect of chitosan on surgically created one-wall intrabony defects in beagle dogs. J. Clin. Periodontol. 2003;30:443-453.

    Not in our library10.1034/j.1600-051x.2003.10283.x

  114. 114.

    Eap S., Ferrand A., Schiavi J., Keller L., Kokten T., Fioretti F., Mainard D., Ladam G., Benkirane-Jessel N. Collagen implants equipped with ’fish scale’-like nanoreservoirs of growth factors for bone regeneration. Nanomed. (Lond). 2014;9:1253-1261.

    Not in our library10.2217/nnm.13.122

  115. 115.

    Zhang Y., Shi B., Li C., Wang Y., Chen Y., Zhang W., Luo T., Cheng X. The synergetic bone-forming effects of combinations of growth factors expressed by adenovirus vectors on chitosan/collagen scaffolds. J. Control. Release. 2009;136:172-178.

    Not in our library10.1016/j.jconrel.2009.02.016

  116. 116.

    Zhang Q., Hubenak J., Iyyanki T., Alred E., Turza K.C., Davis G., Chang E.I., Branch-Brooks C.D., Beahm E.K., Butler C.E. Engineering vascularized soft tissue flaps in an animal model using human adipose-derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle. Biomaterials. 2015;73:198-213.

    Not in our library10.1016/j.biomaterials.2015.09.024

  117. 117.

    Shi S., Cheng X., Wang J., Zhang W., Peng L., Zhang Y. RhBMP-2 microspheres-loaded chitosan/collagen scaffold enhanced osseointegration: An experiment in dog. J. Biomater. Appl. 2009;23:331-346.

    Not in our library10.1177/0885328208090013

  118. 118.

    Elango J., Saravanakumar K., Rahman S.U., Henrotin Y., Regenstein J.M., Wu W., Bao B. Chitosan-Collagen 3D Matrix Mimics Trabecular Bone and Regulates RANKL-Mediated Paracrine Cues of Differentiated Osteoblast and Mesenchymal Stem Cells for Bone Marrow Macrophage-Derived Osteoclastogenesis. Biomolecules. 2019;9:173.

    Not in our library10.3390/biom9050173

  119. 119.

    Ansarizadeh M., Mashayekhan S., Saadatmand M. Fabrication, modeling and optimization of lyophilized advanced platelet rich fibrin in combination with collagen-chitosan as a guided bone regeneration membrane. Int. J. Biol. Macromol. 2019;125:383-391.

    Not in our library10.1016/j.ijbiomac.2018.12.078

  120. 120.

    Sowjanya J.A., Singh J., Mohita T., Sarvanan S., Moorthi A., Srinivasan N., Selvamurugan N. Biocomposite scaffolds containing chitosan/alginate/nano-silica for bone tissue engineering. Colloids Surf. B Biointerfaces. 2013;109:294-300.

    Not in our library10.1016/j.colsurfb.2013.04.006

  121. 121.

    Kim H.-L., Jung G.-Y., Yoon J.-H., Han J.-S., Park Y.-J., Kim D.-G., Zhang M., Kim D.-J. Preparation and characterization of nano-sized hydroxyapatite/alginate/chitosan composite scaffolds for bone tissue engineering. Mater. Sci. Eng. C Mater. Biol. Appl. 2015;54:20-25.

    Not in our library10.1016/j.msec.2015.04.033

  122. 122.

    Jin H.-H., Kim D.-H., Kim T.-W., Shin K.-K., Jung J.S., Park H.-C., Yoon S.-Y. In vivo evaluation of porous hydroxyapatite/chitosan–alginate composite scaffolds for bone tissue engineering. Int. J. Biol. Macromol. 2012;51:1079-1085.

    Not in our library10.1016/j.ijbiomac.2012.08.027

  123. 123.

    Florczyk S.J., Leung M., Li Z., Huang J.I., Hopper R.A., Zhang M. Evaluation of three-dimensional porous chitosan-alginate scaffolds in rat calvarial defects for bone regeneration applications. J. Biomed. Mater. Res. A. 2013;101:2974-2983.

    Not in our library10.1002/jbm.a.34593

  124. 124.

    Teimouri A., Ebrahimi R., Emadi R., Beni B.H., Chermahini A.N. Nano-composite of silk fibroin-chitosan/Nano ZrO2 for tissue engineering applications: Fabrication and morphology. Int. J. Biol. Macromol. 2015;76:292-302.

    Not in our library10.1016/j.ijbiomac.2015.02.023

  125. 125.

    Lima P.A.L., Resende C.X., de Almeida Soares G.D., Anselme K., Almeida L.E. Preparation, characterization and biological test of 3D-scaffolds based on chitosan, fibroin and hydroxyapatite for bone tissue engineering. Mater. Sci. Eng. C Mater. Biol. Appl. 2013;33:3389-3395.

    Not in our library10.1016/j.msec.2013.04.026

  126. 126.

    Tong S., Xu D.-P., Liu Z.-M., Du Y., Wang X.-K. Synthesis of and in vitro and in vivo evaluation of a novel TGF-β1-SF-CS three-dimensional scaffold for bone tissue engineering. Int. J. Mol. Med. 2016;38:367-380.

    Not in our library10.3892/ijmm.2016.2651

  127. 127.

    Niu X., Fan Y., Liu X., Li X., Li P., Wang J., Sha Z., Feng Q. Repair of bone defect in femoral condyle using microencapsulated chitosan, nanohydroxyapatite/collagen and poly(L-lactide)-based microsphere-scaffold delivery system. Artif. Organs. 2011;35:E119-E128.

    Not in our library10.1111/j.1525-1594.2011.01274.x

  128. 128.

    Sainitya R., Sriram M., Kalyanaraman V., Dhivya S., Saravanan S., Vairamani M., Sastry T.P., Selvamurugan N. Scaffolds containing chitosan/carboxymethyl cellulose/mesoporous wollastonite for bone tissue engineering. Int. J. Biol. Macromol. 2015;80:481-488.

    Not in our library10.1016/j.ijbiomac.2015.07.016

  129. 129.

    Miranda S.C.C.C., Silva G.A.B., Mendes R.M., Abreu F.A.M., Caliari M.V., Alves J.B., Goes A.M. Mesenchymal stem cells associated with porous chitosan–gelatin scaffold: A potential strategy for alveolar bone regeneration. J. Biomed. Mater. Res. Part. A. 2012;100A:2775-2786.

    Not in our library10.1002/jbm.a.34214

  130. 130.

    Olad A., Farshi Azhar F. The synergetic effect of bioactive ceramic and nanoclay on the properties of chitosan–gelatin/nanohydroxyapatite–montmorillonite scaffold for bone tissue engineering. Ceram. Int. 2014;40:10061-10072.

    Not in our library10.1016/j.ceramint.2014.04.010

  131. 131.

    Kavya K.C., Jayakumar R., Nair S., Chennazhi K.P. Fabrication and characterization of chitosan/gelatin/nSiO2 composite scaffold for bone tissue engineering. Int. J. Biol. Macromol. 2013;59:255-263.

    Not in our library10.1016/j.ijbiomac.2013.04.023

  132. 132.

    Serra I.R., Fradique R., Vallejo M.C.S., Correia T.R., Miguel S.P., Correia I.J. Production and characterization of chitosan/gelatin/β-TCP scaffolds for improved bone tissue regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 2015;55:592-604.

    Not in our library10.1016/j.msec.2015.05.072

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    Acevedo C.A., Olguín Y., Briceño M., Forero J.C., Osses N., Díaz-Calderón P., Jaques A., Ortiz R. Design of a biodegradable UV-irradiated gelatin-chitosan/nanocomposed membrane with osteogenic ability for application in bone regeneration. Mater. Sci. Eng. C Mater. Biol. Appl. 2019;99:875-886.

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    Maji K., Dasgupta S., Kundu B., Bissoyi A. Development of gelatin-chitosan-hydroxyapatite based bioactive bone scaffold with controlled pore size and mechanical strength. J. Biomater. Sci. Polym. Ed. 2015;26:1190-1209.

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    Puvaneswary S., Talebian S., Raghavendran H.B., Murali M.R., Mehrali M., Afifi A.M., Kasim N.H.B.A., Kamarul T. Fabrication and in vitro biological activity of βTCP-Chitosan-Fucoidan composite for bone tissue engineering. Carbohydr. Polym. 2015;134:799-807.

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    Jing X., Mi H.-Y., Peng J., Peng X.-F., Turng L.-S. Electrospun aligned poly(propylene carbonate) microfibers with chitosan nanofibers as tissue engineering scaffolds. Carbohydr. Polym. 2015;117:941-949.

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    Zhang S., Prabhakaran M.P., Qin X., Ramakrishna S. Biocomposite scaffolds for bone regeneration: Role of chitosan and hydroxyapatite within poly-3-hydroxybutyrate-co-3-hydroxyvalerate on mechanical properties and in vitro evaluation. J. Mech. Behav. Biomed. Mater. 2015;51:88-98.

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    Yao Q., Li W., Yu S., Ma L., Jin D., Boccaccini A.R., Liu Y. Multifunctional chitosan/polyvinyl pyrrolidone/45S5 Bioglass® scaffolds for MC3T3-E1 cell stimulation and drug release. Mater. Sci. Eng. C Mater. Biol. Appl. 2015;56:473-480.

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    Sajesh K.M., Jayakumar R., Nair S.V., Chennazhi K.P. Biocompatible conducting chitosan/polypyrrole-alginate composite scaffold for bone tissue engineering. Int. J. Biol. Macromol. 2013;62:465-471.

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    Pon-On W., Charoenphandhu N., Teerapornpuntakit J., Thongbunchoo J., Krishnamra N., Tang I.-M. Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)-bioglass/chitosan-collagen composite scaffolds: A bone tissue engineering applications. Mater. Sci. Eng. C Mater. Biol. Appl. 2014;38:63-72.

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    Peng L., Zhou Y., Lu W., Zhu W., Li Y., Chen K., Zhang G., Xu J., Deng Z., Wang D. Characterization of a novel polyvinyl alcohol/chitosan porous hydrogel combined with bone marrow mesenchymal stem cells and its application in articular cartilage repair. BMC Musculoskelet. Disord. 2019;20:257.

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    De la Riva B., Nowak C., Sánchez E., Hernández A., Schulz-Siegmund M., Pec M.K., Delgado A., Evora C. VEGF-controlled release within a bone defect from alginate/chitosan/PLA-H scaffolds. Eur. J. Pharm. Biopharm. 2009;73:50-58.

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    Keller L., Offner D., Schwinté P., Morand D., Wagner Q., Gros C., Bornert F., Bahi S., Musset A.-M., Benkirane-Jessel N., et al. Active Nanomaterials to Meet the Challenge of Dental Pulp Regeneration. Mater. (Basel). 2015;8:7461-7471.

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    Zein N., Harmouch E., Lutz J.-C., Fernandez De Grado G., Kuchler-Bopp S., Clauss F., Offner D., Hua G., Benkirane-Jessel N., Fioretti F. Polymer-Based Instructive Scaffolds for Endodontic Regeneration. Mater. (Basel). 2019;12:2347.

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    Liao F., Chen Y., Li Z., Wang Y., Shi B., Gong Z., Cheng X. A novel bioactive three-dimensional beta-tricalcium phosphate/chitosan scaffold for periodontal tissue engineering. J. Mater. Sci. Mater. Med. 2010;21:489-496.

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    Albuquerque M.T.P., Valera M.C., Nakashima M., Nör J.E., Bottino M.C. Tissue-engineering-based strategies for regenerative endodontics. J. Dent. Res. 2014;93:1222-1231.

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    Bordini E.A.F., Cassiano F.B., Silva I.S.P., Usberti F.R., Anovazzi G., Pacheco L.E., Pansani T.N., Leite M.L., Hebling J., de Souza Costa C.A., et al. Synergistic potential of 1α,25-dihydroxyvitamin D3 and calcium-aluminate-chitosan scaffolds with dental pulp cells. Clin. Oral Investig. 2019;1-12.

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    Ducret M., Montembault A., Josse J., Pasdeloup M., Celle A., Benchrih R., Mallein-Gerin F., Alliot-Licht B., David L., Farges J.-C. Design and characterization of a chitosan-enriched fibrin hydrogel for human dental pulp regeneration. Dent. Mater. 2019;35:523-533.

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    Zhu N., Chatzistavrou X., Ge L., Qin M., Papagerakis P., Wang Y. Biological properties of modified bioactive glass on dental pulp cells. J. Dent. 2019;83:18-26.

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    Loyola-Rodríguez J.P., Torres-Méndez F., Espinosa-Cristobal L.F., García-Cortes J.O., Loyola-Leyva A., González F.J., Soto-Barreras U., Nieto-Aguilar R., Contreras-Palma G. Antimicrobial activity of endodontic sealers and medications containing chitosan and silver nanoparticles against Enterococcus faecalis. J. Appl. Biomater. Funct. Mater. 2019;17:2280800019851771.

    Not in our library10.1177/2280800019851771

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