Present and future of tissue engineering scaffolds for dentin-pulp complex regeneration

Abstract

More than two thirds of the global population suffers from tooth decay, which results in cavities with various levels of lesion severity. Clinical interventions to treat tooth decay range from simple coronal fillings to invasive root canal treatment. Pulp capping is the only available clinical option to maintain the pulp vitality in deep lesions, but irreversible pulp inflammation and reinfection are frequent outcomes for this treatment. When affected pulp involvement is beyond repair, the dentist has to perform endodontic therapy leaving the tooth non-vital and brittle. On-going research strategies have failed to overcome the limitations of existing pulp capping materials so that healthy and progressive regeneration of the injured tissues is attained. Preserving pulp vitality is crucial for tooth homeostasis and durability, and thus, there is a critical need for clinical interventions that enable regeneration of the dentin-pulp complex to rescue millions of teeth annually. The identification and development of appropriate biomaterials for dentin-pulp scaffolds are necessary to optimize clinical approaches to regenerate these hybrid dental tissues. Likewise, a deep understanding of the interactions between the micro-environment, growth factors, and progenitor cells will provide design basis for the most fitting scaffolds for this purpose. In this review, we first introduce the long-lasting clinical dental problem of rescuing diseased tooth vitality, the limitations of current clinical therapies and interventions to restore the damaged tissues, and the need for new strategies to fully revitalize the tooth. Then, we comprehensively report on the characteristics of the main materials of naturally-derived and synthetically-engineered polymers, ceramics, and composite scaffolds as well as their use in dentin-pulp complex regeneration strategies. Finally, we present a series of innovative smart polymeric biomaterials with potential to overcome dentin-pulp complex regeneration challenges.

Keywords: dentin-pulp complex; endondontics; multifunctional scaffolds; natural scaffolds; synthetic scaffolds; tissue engineering.

FIGURE 1

Strategies for developing new smart tissue engineering scaffolds for dentine-pulp complex regeneration (The authors would like to thank the “Pérez et al., 2013” for permission to reuse this figure). See text for details regarding each of the three main strategies. ECM: extracellular matrix; GFs: growth factors; SAP: self-assembled peptide [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Alginate/collagen hydrogel customized to promote stem cell self-renewal with a micro-environmental switch to direct differentiation. (a) Alginate serves as structural modulator to prevent the adhesive and fibrous network created by collagen. Upon switching (chelation of Ca2+ ions), alginate is removed and collagen fibres are generated forming an adhesive micro-environment. (c) Quantitation of alginate and collagen before and after switching. (d) Spectroscopy measuring collagen fibre character during cross-linking and switching of hydrogels. Alginate prevents complete collagen network formation until chelation and washout (The authors would like to thank the “Dixon et al., 2014” for permission to reuse this figure) [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Schematic diagram of preparation of PFP-C nanocomposites and their fibrogenic capacity on hiPS-MSCs. (1) A PF solution with CTGF was added on the top of a PCL mesh. (2) UV light exposure to crosslink PF. (3) A free-standing PFP-C composite was formed. (4) hiPS-MSCs were seeded on the composite. (5) Fibrogenesis process synergetically promoted by the adhesive motif on PFP and the signalling induction of CTGF. PF: Poly(ethylene glycol)-Fibrinogen; PCL: Poly(ε-caprolactone); PFP: integrated PCL fibers and PF hydrogel into one 3D scaffold; CTGF: connective tissue growth factor; PFP-C: the CTGF loaded fiber/hydrogel composite; (hiPS-MSCs): human induced pluripotent stem cells derived mesenchymal stem cells. (The authors would like to thank the “Xu et al., 2015” for permission to reuse this figure) [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Electrospun fibrillar scaffolds made of elastin-like recombinant polymers. Scaffolds with a statherin-derived peptide sequence and conjugated antimicrobial GL13K peptides before (a) and after (b) intrafibrillar mineralization