Recent advances in periodontal regeneration: A biomaterial perspective

Abstract

Periodontal disease (PD) is one of the most common inflammatory oral diseases, affecting approximately 47% of adults aged 30 years or older in the United States. If not treated properly, PD leads to degradation of periodontal tissues, causing tooth movement, and eventually tooth loss. Conventional clinical therapy for PD aims at eliminating infectious sources, and reducing inflammation to arrest disease progression, which cannot achieve the regeneration of lost periodontal tissues. Over the past two decades, various regenerative periodontal therapies, such as guided tissue regeneration (GTR), enamel matrix derivative, bone grafts, growth factor delivery, and the combination of cells and growth factors with matrix-based scaffolds have been developed to target the restoration of lost tooth-supporting tissues, including periodontal ligament, alveolar bone, and cementum. This review discusses recent progresses of periodontal regeneration using tissue-engineering and regenerative medicine approaches. Specifically, we focus on the advances of biomaterials and controlled drug delivery for periodontal regeneration in recent years. Special attention is given to the development of advanced bio-inspired scaffolding biomaterials and temporospatial control of multi-drug delivery for the regeneration of cementum-periodontal ligament-alveolar bone complex. Challenges and future perspectives are presented to provide inspiration for the design and development of innovative biomaterials and delivery system for new regenerative periodontal therapy.

Graphical abstract

Fig. 1

Schematic illustration of the anatomy of periodontal tissues, periodontal defect, scaffolds of tissue engineering approach and drug delivery system.

Fig. 2

Schematic illustration of the design of hierarchical injectable nanofibrous microspheres for bone regeneration. BMP-2 is encapsulated into heparin-conjugated gelatin nanospheres, which are further immobilized in nanofibrous PLLA microspheres. Adapted with permission from Ref. [143].

Fig. 3

Development of multi-drugs delivery systems. (A) A PLGA-lovastatin-chitosan-tetracycline release system, in which tetracycline was loaded in chitosan and lovastatin was loaded in PLGA microparticles. (B) The sequential release of tetracycline and lovastatin effectively controlled local infection and promote new bone and cementum regeneration. Adapted with permission from Ref. [150]. (C) The design of four drugs delivery system using a layer-by-layer technique. (D) The release profiles confirmed the sequential releases of the drugs from the system in vitro. Adapted with permission from Ref. [148].

Fig. 4

Development of micropatterned scaffolds to guide collagen fiber orientation of PDL. (A) The 3D printed micropatterned matrx with various geometry (width, W and depth, D of the grooves) controlled the orientation of collagen deposited on the matrix. (B) The 3D printing technology was used to create angulated microgroove patterns that were used control cell orientations such as parallel (0°), oblique (45°) and perpendicular (90°) angulations. Adapted with permission from Refs. [31,79].

Fig. 5

An immunomodulatory approach to enhance alveolar bone healing and regeneration. The nanofibrous microsphere mimic the architecture of bone ECM and switched the transition of macrophages from M1 to M2 phenotypes; therefore, enhanced alveolar bone healing. Adapted with permission from Ref. [168].

Fig. 6

Combination of cell sheet technology with bone and PDL scaffolds to regenerate cementum-PDL-alveolar bone. (A) Fabrication scheme showing the combination of PDL and bone compartments with a dentin slice. The bone and PDL layers were fabricated using fused deposition and electrospinning, respectively. (B) SEM image of the biphasic scaffold showing the fusion of the electrospun fibers onto the fused deposition component. (C) Subcutaneously transplanted the construct to induce periodontal regeneration in vivo. (D) PDL-like and (E) cementum-like tissues formation after transplantation for eight weeks. (F) CaP was coated on the PCL fused deposition compartment. (G) The CaP-coated scaffold enhanced bone formation. Adapted with permission from Refs. [88,166].