Periodontitis is a globally prevalent chronic inflammatory disease that leads to periodontal pocket formation and eventually destroys tooth-supporting structures. Hence, the drastic increase in dental implants for periodontitis has become a severe clinical issue. Injectable hydrogel based on extracellular matrix (ECM) is highly biocompatible and tissue-regenerative with tailor-made mechanical properties and high payload capacity for in situ delivery of bioactive molecules to treat periodontitis. This therapeutic tool not only enhances the drug release efficiency and treatment efficacy but also reduces operation time. Nevertheless, it remains challenging to optimize the mechanical properties and intelligent control drug release rate of injectable hydrogels to achieve the highest therapeutic outcome. Literature precedent has shown the modulation of polymer backbones (synthetic polymers, natural polysaccharides, and proteins), crosslinking strategies, other bioactive constituents, and potentially the incorporation of nanomaterials that overall improve the desirable physiochemical and biological performances as well as biodegradability. In this review, we summarize the recent advances in the development, design, and material characterizations of common injectable hydrogels. Furthermore, we highlight cutting-edge representative examples of polysaccharide-, protein- and nanocomposite-based hydrogels that mediate regenerative factors and anti-inflammatory drugs for periodontal regeneration. Finally, we express our perspectives on potential challenges and future development of multifunctional injectable hydrogels for periodontitis.

Centre for Orthopaedic Research School of Biomedical Science The University of Western Australia Nedlands WA 6009 Australia

Department of Biomedical Engineering Chang Gung University Taoyuan 33302 Taiwan

Department of Orthopaedic Surgery New Taipei Municipal Tucheng Hospital New Taipei 236 Taiwan

Department of Periodontics Chang Gung Memorial Hospital Taipei 10507 Taiwan

Laboratory for Marine Drugs and Bioproducts Qingdao Marine Science and Technology Center Qingdao 266237 China

Materials for Medicine Research Group School of Medicine The Royal College of Surgeons in Ireland Medical University of Bahrain Kingdom of Bahrain

Materials Science and Engineering University of Utah 122 S Central Campus Drive Room 304 Salt Lake City 84112 Utah USA

New Technologies Research Centre University of West Bohemia Univerzitní 8 301 00 Pilsen Czech Republic

School of Medicine and Pharmacy Ocean University of China Qingdao 266003 China

University of West Bohemia Faculty of Mechanical Engineering Department of Materials and Engineering Metallurgy Univerzitní 22 301 00 Pilsen Czech Republic

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