Injectable Hydrogels in Dentistry: Advances and Promises


Austin J Dent. 2j014;1(1): 1001.

Injectable Hydrogels in Dentistry: Advances and Promises

Wei Seong Toh1,2*

1Faculty of Dentistry, National University of Singapore, Singapore

2Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore

*Corresponding author: Wei Seong Toh, Faculty of Dentistry, National University of Singapore, 11 Lower Kent Ridge Road, Singapore 119083

Received: April 22, 2014; Accepted: April 25, 2014; Published: April 28, 2014


Hydrogels; Stem Cells; Craniofacial; Oral; Dentistry; Tissue Engineering


Hydrogels are natural or synthetic polymers with high waterabsorbing capacity that are widely investigated for vast applications in regenerative medicine [1]. In recent years, injectable hydrogels have emerged as a promising biomaterial for therapeutic delivery of cells and bioactive molecules for tissue regeneration in dentistry and medicine because of their tunable tissue–like properties, controllability of degradation and release behavior, adaptability in a clinical setting for minimally–invasive surgical procedures, and ability to conform to the three–dimensional (3–D) defect upon gelling [2].

Natural hydrogels are often used in regenerative applications, due to their innate biological characteristics and resemblance to the native extracellular matrix (ECM). Some of the natural polymers include collagen, fibrin, hyaluronic acid, gelatin, chitosan and alginate. On contrary, synthetic hydrogels have finely–tuned properties such as degradation and mechanics, and are highly–reproducible with little batch–to–batch variation. The most commonly used synthetic hydrogels for regenerative applications are based on poly (ethylene glycol) (PEG). Of note, these highly–hydrated networks can be held together via physical or chemical cross links, can be made biodegradable, and responsive to specific stimuli such as pH and temperature, and can be engineered to deliver therapeutic cells and bioactive factors in a sustained and controlled fashion.

In craniofacial and dental tissue engineering, a paradigm shift is taking place from using synthetic implants and tissue grafts to tissue engineering approach employing biomimetic biomaterial scaffolds, particularly injectable hydrogels integrated with cells and bioactive molecules to regenerate a myriad of tissues including cartilage, bone, nerves, blood vessels and soft tissues (i.e. muscle, subcutaneous fat and skin). Similarly, in regenerative endodontic, injectable hydrogels have demonstrated the feasibility of delivering dental pulp stem cells, supporting matrix (e.g. enamel derivative [3]) and growth factors (e.g. stromal–derived growth factor (SDF)–α1, fibroblast growth factor (FGF)–2, and bone morphogenetic protein (BMP)–7) to support formation of the dentin–pulp complex [4]. A recent advance in tissue engineering further demonstrated the potential of the ‘homing’ approach for craniofacial and dentin–pulp regeneration, using biomaterial scaffold and bioactive molecules to activate endogenous cell migration and tissue repair [5].

Recent advances in materials science have enabled fabrication of synthetic and natural hydrogels with independent tuning of chemical composition and physical properties including stiffness. For example, the hyaluronic acid–tyramine (HA–Tyr) hydrogels were formed through the oxidative coupling of tyramine moieties, which was catalysed by horseradish peroxides (HRP) and hydrogen peroxide (H2O2) [6]. The gelation rates and stiffness of the hydrogels can be independently tuned by varying the HRP and H2O2, respectively. In cartilage tissue engineering, it was observed that the tunable 3–D microenvironment of the HA–Tyr hydrogels modulated mesenchymal stem cell chondrogenesis, where cellular condensation and cartilage formation were enhanced in the lower cross–linked matrices [6].

To overcome the possible limitations of individual material, composite hydrogels and hybrid systems have gained popularity in recent years. In bone tissue engineering, composite hydrogels may be created by blending two different polymeric materials and/or incorporation with inorganic phases such as hydroxyapatite, calcium phosphate and bio glasses to confer improvement to mechanical properties as well as added functionality for bone regeneration. Among the composite hydrogels, thermo–responsive chitosanglycero phosphate hydrogel composite possess beneficial antibacterial and osteo inductive properties, and flexibility in blending with other materials such as the collagen [7] and gelatin [8], making the composite hydrogels an attractive candidate for craniofacial bone tissue engineering. In adipose tissue engineering, composite and multifunctional hydrogels may be fabricated by incorporating the decellularized adipose matrix [9] into the hydrogels matrix to recreate the adipose–like environment for adipose tissue regeneration [10].

Supra molecular hydrogels are the next–generation materials to enter the biomedical arena [11]. These materials are 3–D entities built from cross linking agents which bond non–covalently (via hydrogen bonds, p–p stacking and Vander Waals interactions) to form hydrogels. The use of injectable supra molecular hydrogels for tissue engineering is promising owing to their ability to deliver therapeutics, including cells and bioactive molecules in a highly–sustained and controlled manner [12].

Apart from expanding hydrogels chemistries, emerging tools and techniques including photo patterning [13], electro spinning [14] and co–culture of multiple cell types [15] are also being developed and applied towards engineering of multi–scaled and multi–layered hydrogel systems for regenerative applications [16]. Notably, there have been new and cell–friendly efforts to improve the porosity of hydrogels to enhance cellular infiltration through incorporation of stimuli–responsive microspheres [17] and microfibers [18] that may be dissolved in a controlled manner by specific changes in pH, temperature or exposure to enzymes. Utilizing these techniques may aid in the spatially controlled organization of multiple cell types and bioactive molecules and facilitate the progress towards regeneration of craniofacial complex tissues within the oral and craniofacial region.

Looking into the future, the design of injectable hydrogels that can be injected into the defect site and support cell infiltration and tissue in growth will be greatly explored. Hydrogels may be decorated with specific ECM ligands to recreate the naïve tissue environment and deliver the bioactive molecules in specific fashion (simultaneous vs. sequential) to orchestrate both exogenous and endogenous cell responses towards tissue regeneration. With great promise provided by these hydrogels, the issues regarding safety, degradation and clearance should also be addressed. New material chemistries and cross linking methods would be developed to enhance the material biocompatibility, functionality as well as the mechanical properties. Fundamental studies of cell–materials interactions will aid in guiding the design and development of the next–generation hydrogel systems for tissue repair and regeneration. These advances in h0079drogel design and engineering will continue to grow and aid in our future design of customized hydrogel systems, and guide the development of future therapies in dentistry.


  1. Hoffman AS. Hydrogels for biomedical applications. Advanced Drug Delivery Reviews. 2002; 54: 3-12.
  2. Toh WS, Spector M, Lee EH, Cao T. Biomaterial-Mediated Delivery of Microenvironmental Cues for Repair and Regeneration of Articular Cartilage. Molecular Pharmaceutics. 2011; 8: 994-1001.
  3. Park SJ, Li Z, Hwang IN, Huh KM, Min K-S. Glycol Chitin-based Thermoresponsive Hydrogel Scaffold Supplemented with Enamel Matrix Derivative Promotes Odontogenic Differentiation of Human Dental Pulp Cells. Journal of Endodontics. 2013; 39: 1001-1007.
  4. Suzuki T, Lee CH, Chen M, Zhao W, Fu SY, Qi JJ, et al. Induced Migration of Dental Pulp Stem Cells for in vivo Pulp Regeneration. Journal of Dental Research. 2011; 90: 1013-1018.
  5. Nie H, Lee C, Tan J, Lu C, Mendelson A, Chen M, et al. Musculoskeletal tissue engineering by endogenous stem/progenitor cells. Cell Tissue Res. 2012; 347: 665-676.
  6. Toh WS, Lim TC, Kurisawa M, Spector M. Modulation of mesenchymal stem cell chondrogenesis in a tunable hyaluronic acid hydrogel microenvironment. Biomaterials. 2012; 33: 3835-3845.
  7. Wang L, Stegemann JP. Thermogelling chitosan and collagen composite hydrogels initiated with beta-glycerophosphate for bone tissue engineering. Biomaterials. 2010; 31: 3976-3985.
  8. Cheng YH, Yang SH, Liu CC, Gefen A, Lin FH. Thermosensitive hydrogel made of ferulic acid-gelatin and chitosan glycerophosphate. Carbohydrate Polymers. 2013; 92: 1512-1519.
  9. Lu Q, Li M, Zou Y, Cao T. Delivery of basic fibroblast growth factors from heparinized decellularized adipose tissue stimulates potent de novo adipogenesis. Journal of Controlled Release. 2014; 174: 43-50.
  10. Cheung HK, Han TTY, Marecak DM, Watkins JF, Amsden BG, Flynn LE. Composite hydrogel scaffolds incorporating decellularized adipose tissue for soft tissue engineering with adipose-derived stem cells. Biomaterials. 2014; 35: 1914-1923.
  11. Appel EA, del Barrio J, Loh XJ, Scherman OA. Supramolecular polymeric hydrogels. Chemical Society Reviews. 2012; 41: 6195-6214.
  12. Appel EA, Loh XJ, Jones ST, Dreiss CA, Scherman OA. Sustained release of proteins from high water content supramolecular polymer hydrogels. Biomaterials. 2012; 33: 4646-4652.
  13. Mosiewicz KA, Kolb L, van der Vlies AJ, Martino MM, Lienemann PS, Hubbell JA, et al. In situ cell manipulation through enzymatic hydrogel photopatterning. Nat Mater. 2013; 12: 1072-1078.
  14. Loh XJ, Peh P, Liao S, Sng C, Li J. Controlled drug release from biodegradable thermoresponsive physical hydrogel nanofibers. Journal of Controlled Release. 2010; 143: 175-182.
  15. Chen YC, Lin RZ, Qi H, Yang Y, Bae H, Melero-Martin JM, et al. Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels. Advanced Functional Materials. 2012; 22: 2027-2039.
  16. Toh WS, Loh XJ. Advances in Hydrogel Delivery Systems for Tissue Regeneration. Materials Science and Engineering: C.
  17. Lau TT, Ho LW, Wang D-A. Hepatogenesis of murine induced pluripotent stem cells in 3D micro-cavitary hydrogel system for liver regeneration. Biomaterials. 2013; 34: 6659-6669.
  18. Bellan LM, Pearsall M, Cropek DM, Langer R. A 3D Interconnected Microchannel Network Formed in Gelatin by Sacrificial Shellac Microfibers. Advanced Materials. 2012; 24: 5187-5191.

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Citation: Toh WS. Injectable Hydrogels in Dentistry: Advances and Promises. Austin J Dent. 2j014;1(1): 1001. ISSN:2381-9189

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