Smart injectable hydrogels for periodontal regeneration: Recent advancements in biomaterials and biofabrication strategies

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.