Abstract

Different approaches to develop engineered scaffolds for periodontal tissues regeneration have been proposed. In this review, innovations in stem cell technology and scaffolds engineering focused primarily on Periodontal Ligament (PDL) regeneration are discussed and analyzed based on results from pre-clinical in vivo studies and clinical trials. Most of those developments include the use of polymeric materials with different patterning and surface nanotopography and printing of complex and sophisticated multiphasic composite scaffolds with different compartments to accomodate for the different periodontal tissues’ architecture. Despite the increased effort in producing these scaffolds and their undoubtable efficiency to guide and support tissue regeneration, appropriate source of cells is also needed to provide new tissue formation and various biological and mechanochemical cues from the Extraccellular Matrix (ECM) to provide biophysical stimuli for cell growth and differentiation. Cell sheet engineering is a novel promising technique that allows obtaining cells in a sheet format while preserving ECM components. The right combination of those factors has not been discovered yet and efforts are still needed to ameliorate regenerative outcomes towards the functional organisation of the developed tissues.

Highlights

  • Periodontitis is a bacteria-driven infectious oral condition that can lead to severe degeneration of periodontal tissues with high prevalence (42.2%) in adults aged 30 years and older [1]

  • The included studies used a variety of biomaterials in an attempt to simulate the orthotopic conditions and ectopically assess the potential for periodontal regeneration of each cell sheet, such as ceramic bovine bone (CBB), chemical conditioned root dentin (CCRD), dentin block, polyglycolic acid (PGA) film, gelfoam scaffold, treated dentin matrix (TDM), hydroxyapatite/tricalcium phosphate (HA/TCP), titanium (Ti), teeth roots, platelet-rich fibrin (PRF) fabricated into bioabsorbable fibrin scaffolds, decalcified dentin matrix (DDM), polycaprolactone (PCL) scaffold, Matrigel, and micro/macro-porous biphasic calcium phosphate (MBCP) blocks

  • The in vivo application of cell sheets from the coculture of periodontal ligament stem cells (PDLSCs) with either urine-derived stem cells (USCs) or jaw BMMSCs resulted in increased expression levels of bone- and extracellular matrix (ECM)-related genes and proteins and led to the formation of a complex tissue like the native periodontal tissue [87–89]

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Summary

Introduction

Periodontitis is a bacteria-driven infectious oral condition that can lead to severe degeneration of periodontal tissues with high prevalence (42.2%) in adults aged 30 years and older [1]. Bone tissue destruction occurs in forms of craterlike defects around teeth roots These intrabony defects constitute a major challenge to periodontal disease treatment; they can be treated through conventional root scaling and planning healing but without the formation of new supporting tissue [2], while remaining periodontal pockets can cause aesthetic problems and act as triggers to further destruction. The outermost goal of periodontal therapy is the simultaneous regeneration of all periodontal tissues, i.e., new alveolar bone, cementum, and periodontal ligament (PDL) Towards this direction, surgical treatment is based on the Guided Tissue Regeneration (GTR) approach, during which appropriate membranes are utilized to protect bone defect from epithelial tissue downgrowth, allowing the healing and regeneration of the underlying tissues [3]. The perpendicular alignment of new highly organized collagen fibers, inserted into the regenerated cementum and bone, is the most fundamental aspect of the whole periodontal tissue complex regeneration and emerging efforts are dedicated to this ultimate goal

Periodontal Ligament
Cementum
Cell-Guided PDL Regeneration
In Vivo Studies
Cell Sheet Engineering
Results
Periodontal Defect Model
Major Findings
Subcutaneous Placement Model
Other Models
Clinical Studies Involving Scaffolds and Growth Factors
Clinical Studies Involving Caffolds Combined with Cells
Discussion and Concluding
Methods
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