Pulp and dentin tissue engineering and regeneration: current progress

Abstract

Dental pulp tissue is vulnerable to infection. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial rubber-like material is employed to treat the infection - commonly known as root-canal therapy. Regeneration of pulp tissue has been difficult as the tissue is encased in dentin without collateral blood supply except from the root apical end. However, with the advent of the concept of modern tissue engineering and the discovery of dental stem cells, regeneration of pulp and dentin has been tested. This article will review the early attempts to regenerate pulp tissue and the current endeavor of pulp and dentin tissue engineering, and regeneration. The prospective outcome of the current advancement in this line of research will be discussed.

Figure 1. Source of dental stem cells and use for dental tissue regeneration

Note DPSCs are from pulp of permanent teeth, SHED from exfoliated primary teeth. SHED have been shown to regenerate pulp, but not dentin as yet [75]. DPSC: Dental pulp stem cell; PDL: Periodontal ligament; PDLSC: Periodontal ligament stem cell; SCAP: Stem cells from apical papilla; SHED: Stem cells from exfoliated deciduous teeth.

Figure 2. Engineering of dental pulp tissue with dental pulp stem cells

(A) Strategy for dental pulp tissue engineering. (B) Biodegradable scaffold is prepared within the root canal and then seeded with stem cells from exfoliated deciduous teeth (SHED) only or SHED mixed with endothelial cells. A tooth slice containing cells is then implanted into the subcutaneous tissue of immunodeficient mice. (C) High magnification of the tooth slice/scaffold showing the interface between scaffold and predentin. (D) Low magnification (×100) of a dental pulp engineered with SHED and primary human dermal microvascular endothelial cells 14 days after implantation in an immunodeficient mouse. (E) High magnification (×400) of the boxed area of the engineered dental pulp presented in (D). Adapted with permission from [75].

Figure 3. Root fragment In vivo model for pulp/dentin regeneration

(A) A human tooth root fragment with enlarged canal space was generated. One end of the canal opening was sealed with MTA cement and the canal filled with poly(D-L-lactide-co-glycolide) (PLG) scaffold seeded with stem cells. The construct was transplanted into the subcutaneous space of severe combined immunodeficiency (SCID) mice. The implanted tooth fragment containing cells/scaffold was removed after several months in the subcutaneous space of SCID mice and processed for analysis. A longitudinal section of the decalcified sample was stained with hematoxylin and eosin. (B) Pulp regeneration using human dental pulp stem cells cast in collagen hydrogel. The implanted tooth fragment containing cells/collagen gel was removed after 3 months in the subcutaneous space of SCID mice and processed for analysis. Arrows indicate the regenerated pulp-like tissue only located near the canal opening. (C) Pulp/dentin regeneration using human dental pulp stem cells seeded in PLG. The implanted tooth fragment containing cells/PLG was removed after 4 months in the subcutaneous space of SCID mice and processed for analysis. Black arrows indicate the demarcation between the subcutaneous tissue from the mouse and the regenerated pulp-like tissue in the canal. Yellow arrows indicate the newly deposited dentin-like mineral tissue onto the canal dentinal walls. (D) Pulp/dentin regeneration using human stem cells from apical papilla seeded in PLG. The implanted tooth fragment containing cells/PLG was removed after 3 months in the subcutaneous space of SCID mice and processed for analysis. Black arrows indicate the demarcation between the subcutaneous tissue from the mouse and the regenerated pulp-like tissue in the canal. Yellow arrows indicate the newly deposited dentin-like mineral tissue onto the canal dentinal walls and MTA surface. Scale bar: 1 mm. MTA: Mineral trioxide aggregate.