Hydrogels in Dentistry – Applications andAdvances

Oral health is considered an important part of general health and quality of life, and oral disease is still a major public health problem in developed countries and a growing burden for developing countries. Common oral diseases include caries, pulp necrosis, periodontitis, oral mucositis and so on. Oral science research has developed rapidly in recent years. Advances have been made in oral tissue engineering and regenerative dentistry thanks to the growing amount of research in fields such as stem cell biology, genetic, molecular engineering, and pathologies that affect the dental tissues.¹ Nevertheless, regeneration is still ruled by the need for three elements that have the goal of restoring functions of affected or diseased organ tissues: ECM, which serves as a scaffold; active biomolecules, that regulate cell growth and differentiation; and mesenchymal cells, needed for the new tissue formation. Thus, in tissue engineering, regeneration will be achieved not only if a structural scaffold is provided, conferring mechanical properties, but also, inducing migration of cell populations.² Dental biomaterials have passed from passive bioinert structures to bioactive materials that have the final goal to return form and function to oral tissues. Hydrogels (HG), have been gaining interest since they possess three-dimensional (3D) polymeric networks with characteristics similar to tissues.³ Hydrogels are 3D Hydrophilic polymer capable of absorbing large amounts of water or biological fluids. It also acts as a scaffold that can be loaded by Cells, Bioactive materials or Growth factors.² According to Slaughter et al, Hydrogels are defined as 3D insoluble polymer matrices created from crosslinked hydrophilic homopolymers, copolymers, or macromers.⁵ It distinguishes itself from other biological materials by its unique characteristics in structure and performance. The polymer network formed by the hydrogel can bind water, which in turn shows good biocompatibility due to the high moisture content. When the hydrogel is combined with biological tissue, its swelling property blurs the boundary between the hydrogel and the tissue, thus reducing the foreign body reactions. In history the use of hydrogels was right from diapers, contact lenses, wound dressings, drug delivery to now the current age of improved agriculture & tissue engineering.² According to Eelkema et al., at present, Hydrogels are used in personal care products, biomaterials, coatings, and plant fertilizers. They also are considered for future applications such as sensing, drug delivery, soft robotics, and biohybrid or biointerfacing material. When hydrogels are compared with other types of biomaterials, they are superior showing proper mechanical strength, porous structure, enhanced biocompatibility, and adjustable biodegradability.³ It has been reported that Implantation of a Chitosan Gel scaffold into a mouse femur demonstrated that it supports the formation of extracellular matrix with minimal inflammation.⁴ Also, potential of hydrogel gel to support new tissue formation and thus provide a promising strategy for bone tissue engineering has been documented in literature. In dentistry the use of hydrogels has been documented for bone regeneration, tissue healing and also it can be used as an effective dental implant surface coating agent. ⁵ This article reviews the uses of hydrogels in Prosthodontics, Oral tissue engineering, Implantology and Research based studies. REVIEW History of hydrogels: The first hydrogel poly-2-hydroxyethyl methacrylate (PHEMA) was created and described in 1960 by Whichterler and Lim. They used it to make moisture-absorbing contact lenses.⁶ Then, in the 1980s, Lim and Sun created calcium-alginate gel composites for islet-droplet microcapsule cell embedding.⁷According to Buwalda et al., there 3 have been three distinct generations of hydrogels. The first generation of hydrogels mostly consisted of gels with diverse crosslinking techniques created by chemically altering a monomer or polymer using an initiator. After this time, in the 1970s, the significance of hydrogels increased to a new level as stimuli-responsive properties were incorporated into the hydrogels, allowing second-generation hydrogels to react to a variety of highly specific stimuli, including changes in pH, temperature, or concentration of certain biomolecules in a solution. The focus switched to the creation of stereo-complexed biomaterials and hydrogels joined through physical interactions in the third-generation hydrogels. These changes prompted scientists to focus their efforts more intently on creating the current “smart hydrogels,” which can be tailored to acquire specific qualities like stimulus responsiveness and adjustable mechanical and other physicochemical properties.⁸ BUILDING BLOCKS FOR THE PREPARATION OF INJECTABLE  HYDROGELS A variety of materials are used to create hydrogels. Generally speaking, there are two types of hydrophilic polymers that are utilized to make hydrogels: natural polymers taken from tissues or other natural sources, and synthetic polymers created utilizing organic chemistry and molecular engineering concepts. Building blocks of synthetic and biocompatible natural polymers are used to create the injectable hydrogels shown in Table 2.⁹ Table 2: Shows biocompatible natural polymer and synthetic polymer building blocks for  the preparation of injectable hydrogels¹⁰ .   TYPES OF HYDROGELS Natural and synthetic biomaterials, such as chitosan, collagen or gelatin, alginate, hyaluronic acid, heparin, chondroitin sulfate, polyethylene glycol (PEG), and polyvinyl alcohol (PVA), are used to form hydrogels. Chemical techniques that use covalent crosslinking produced by enzymes, physical techniques that use weak secondary forces, chemical techniques that use photo-cross-linking, physical techniques that use Michael addition, and chemical techniques that use click chemistry can all be used to create injectable hydrogels that are ion-sensitive, pH- sensitive, or temperature-sensitive.¹⁰
ROLE OF HYDROGELS IN PROSTHODONTICS Hydrogels for Dental Tissue engineering: The combined use of cells, bioactive molecules, and scaffolds such as HG is considered the best approach to achieve tissue regeneration. Dental tissues can be damaged principally by caries and trauma, injuring enamel, dentin, or pulp. Advances in the field of HG could be beneficial to find the ideal scaffold to regenerate every lost tissue. HG can induce changes in cellular processes such as chemotaxis, proliferation, angiogenesis, biomineralization, and expression of specific tissue biomarkers, enhancing the regeneration process. Hydrogels in Dental Implantology: Dental implantology is one of the most attractive & dynamic fields within 9 Prosthodontics. However, in various clinical scenarios, prosthetic & biological complications like abutment screw loosening, fracture, peri-implantitis & marginal bone loss challenge the clinical success & longevity of Implant supported restorations. The number of patients affected by peri-implant diseases (PIDs) is increasing. According to their clinical manifestations, PIDs can be mainly categorized in peri-implant mucositis (PIM) and peri-implantitis (PI). PIM refers to a reversible inflammatory process that affects the soft tissues surrounding an implant, resulting in bleeding on gentle probing and, in some cases, suppuration, erythema, and swelling. The etiology of PIM is the bacterial accumulation and biofilm formation around the dental implant. On the other hand, PI presents not only with inflammation of the soft tissues but is also accompanied by a progressive bone loss that could lead to implant failure. Clinical data have shown that progression from PIM to PI is strongly associated with lack of preventive maintenance; thus, opportune treatment of PIM could prevent the progression to PI. Current treatments against PIM are mainly aimed at eradicating subgingival dysbiosis and restoring homeostasis to microbial communities in the oral cavity. However, clinical data have shown that nonsurgical mechanical approaches, aimed at disinfection of the affected area, often fail due to recolonization of the periodontal or peri-implant pockets by pathogenic bacteria that perpetuate the disease. Moreover, bacterial infection and the subsequent epithelial cell death lead to the release of inflammatory cytokines and chemotactic bacterial peptides, which attract migratory neutrophils. This can worsen implant prognosis, mainly because neutrophil degranulation due to bacterial overload releases tissue-degrading enzymes into the gingival crevice that lead to further tissue trauma. As inflammation extends from the marginal gingiva into the supporting periodontal tissues, PIM could eventually progress to PI and lead to bone loss and implant failure. Therefore, therapeutic strategies that efficiently isolate the affected area to prevent the infiltration of bacteria and other unwanted cells, while also enabling the growth of bone- competent cells (i.e., compartmentalized tissue healing), could improve the clinical outcome of patients with PIDs. Modifications of the Implant surface to minimize these complications, to mediate bone osseointegration & tissue healing are research subjects of major interest. One promising approach consists of functionalizing dental implant materials by incorporating hydrogels with known biomolecules comprising of osteogenic, antibiotic controlled release systems. Additionally, hydrogels can be tailored to obtain the desired geometry for implantation according to the individual needs. The precise control over the microarchitecture, mechanical properties, and degradation rate of hydrogels make them useful alternatives for the controlled delivery of a variety of therapeutic agents in vivo. Hydrogels in Maxillofacial Prosthodontics : Hydrogels are colourless, odourless material. Colour can be artificially modified by pigments and colouring agents acording to the hue. They are non-toxic, non-irritant, non-allergic and hence can be well supported by the host living tissue. They are bioinert and hence do not disturb the nearby biologic tissues. They are stable in light and have optimal transilluminance and hence can be used in areas which are exposed to sunlight like the maxillofacial area. It is light in weight, flexible, and these increases 11 the potential of it to be used as a maxillofacial prosthesis as these areas are more prone to natural creases and wrinkles as the natural appearances of external soft tissues are more important for aesthetics. The patient acceptance of this material hence can be improved. The rigidity of hydrogels can be altered by modifying its properties for using it in different areas of the maxillofacial region accordingly. The shelf life of the hydrogel can be extended up to 3 years by altering its physical and chemical properties and can successfully be used as the definitive maxillofacial material. It is also stable near living tissues as it permits diffusion of oxygen. Shear moduli, compressive moduli, and crosslink densities increase with increase in polyethylene glycol concentration, and the mechanical properties can also be altered by interpenetrating polymer network. This advantage can be used to improve the mechanical properties of and successfully use it as a maxillofacial material. Nano-composite gels are mainly altered hydrogels. These gels show superior mechanical properties such as increased compressive strength, tensile strength, yield stress, and this can be altered by changing or altering the crosslinking and also by reinforcing the carbon nanotube.

Current evidence of Hydrogels

CONCLUSION This article summarizes the various types of hydrogels and their applications in the field of Prosthodontics. Hydrogels has been researched upon in the field of Tissue engineering and results have shown that Hydrogels have the osteoinductive and osteoconductive potential if incorporated with Osteoprogenitor cells and Bone morphogenic proteins which will make it an 16 effective Dental Implant surface coating agent, to enhance osseointegration and Bone Implant Contact. The scope of hydrogels in Prosthodontics is still in its infancy stage and it is important to nuture its growth through the way of invitro and in-vivo studies which involves physicochemical characterization, Degradation profile & Water uptake kinetics tests, Antimicrobial activity test, Antibiotic release profile tests, Biocompatibility tests, Blood interaction tests, Cytotoxicity assay, Animal trials & finally Human clinical trials to make it an authenticated concept in the revolutionizing field of Implant Prosthodontics