Definition, Purpose, and History of Regenerative Endodontics
- Regenerative endodontics replaces damaged structures such as dentin, root structures, and cells of the pulp-dentin complex.
- It aims to promote normal function of the pulp and is an alternative to heal apical periodontitis.
- Regenerative endodontics extends root canal therapy by replacing live tissue in the pulp chamber.
- The ultimate goal is to regenerate tissues and restore the normal function of the dentin-pulp complex.
- Conventional root canal therapy uses biologically inert material, while regenerative endodontics replaces live tissue.
- Dr. Ostby's work in the early 1960s established the concept of regenerative endodontics.
- He hypothesized that the presence of a blood clot within the root canal promotes healing of the pulp.
- Mature teeth diagnosed with pulpal disease underwent pulp space debridement and apical foramen enlargement.
- Intracanal bleeding was evoked, and Kloroperka obturation was placed coronal to the formed blood clot.
- The study showed resolution of inflammation, apical periodontitis, and continued root development in all teeth.

Etiology and Clinical Problems of Regenerative Endodontics
- Trauma is the most common cause of pulpal necrosis in immature permanent teeth.
- Up to 35% of children between 7 and 15 years experience traumatic dental injuries.
- Hertwig epithelial root sheath (HERS) can be damaged during trauma, affecting root formation.
- Dens evaginatus and dens invaginatus are common etiologies of pulp necrosis in immature teeth.
- Continuous trauma from occlusion can lead to rapid pulpal necrosis in the presence of dens evaginatus.
- Early loss of immature permanent teeth can lead to loss of function and interference with phonetics.
- Maxillary and mandibular bone development may be altered in patients with early tooth loss.
- Implants are contraindicated in patients still undergoing cranio skeletal development.
- Regenerative endodontics offers a solution to preserve the natural tooth and avoid implant placement.
- Psychosocial health of young patients can be severely impacted by early tooth loss.

Biological Basis of Regenerative Endodontics
- Successful tissue regeneration relies on appropriate source of stem progenitor cells, growth factors, and scaffolds.
- Mesenchymal stem cells found in dental pulp, apical papilla, and inflamed periapical tissue are optimal for regenerative endodontic applications.
- Other potential sources of postnatal stem cells in the oral environment include tooth germ progenitor cells, dental follicle stem cells, salivary gland stem cells, stem cells from human exfoliated deciduous teeth, periodontal ligament stem cells, oral epithelial stem cells, gingival-derived mesenchymal stem cells, and periosteal stem cells.
- Growth factors play a crucial role in regulating stem cell differentiation and tissue development.
- Scaffolds, such as collagen, dentin, hydrogels, and mineral trioxide aggregate, regulate stem cell differentiation and provide a supportive environment for tissue regeneration.
- Cell homing in dental pulp and dentin regeneration involves cell recruitment and differentiation.
- Stem/progenitor cells differentiate into odontoblasts, pulp fibroblasts, and other niche cells.
- Exogenously delivered and/or endogenous growth factors induce the sprouting of neural fibrils and endothelial cells.
- Successful dental pulp and dentin regeneration requires the recruitment and differentiation of various cell types.
- Cell homing is essential for the success of regenerative procedures in adults.

Regeneration versus Revascularization
- Controversy exists over the terms regeneration versus revascularization.
- Revascularization focuses on restoring blood supply to the pulp space for wound healing.
- Regeneration aims to reproduce the original tissue histology and function.
- Tissue engineering principles are essential in contemporary regenerative endodontic procedures.
- Regenerative endodontics combines stem cells, growth factors, and scaffolds for histological regeneration.
- The primary therapeutic goal of regenerative endodontic procedures is to promote healing, survival, and function of the tooth.
- Regenerative endodontic procedures have better clinical outcomes compared to apexification procedures.
- Secondary therapeutic goal is continued root development.
- Teeth treated with revascularization show a significant increase in root length.
- Regenerative endodontics focuses on patient-centered care and overall well-being.

Clinical Outcomes, Procedure, and Advantages of Regenerative Endodontics
- Regenerative endodontic procedures must be objectively compared with traditional endodontic treatment procedures for immature teeth.
- The primary goal of any endodontic therapy is the resolution of infection and inflammation leading to apical periodontitis.
- Regenerative endodontic procedures require efficient chemical disinfection followed by repair and growth of the tooth.
- Pulpal necrosis in immature teeth often results in incomplete root development and thin root canal walls.
- Clinical outcomes of regenerative endodontics can be observed within 6 months, including resolution of pain and radiographic improvements.
- Regenerative endodontics involves three critical steps: disinfection of the root canal system, induction of bleeding to create a scaffold for stem cells, and coronal sealing of the blood clot.
- The procedure is typically performed in two visits, with the first visit involving isolation of the tooth, removal of the dead pulp, and placement of intracanal medicament.
- During the second visit, bleeding is induced to form a blood clot, followed by placement of an absorbable collagen barrier and mineral trioxide aggregate.
- The tooth is then recalled after 7 days for follow-up and replacement of the coronal barrier.
- This procedure allows for the regeneration of the pulp-dentin complex and continued root development.
- Radiograph images are used to evaluate the outcome of regenerative endodontic treatment.
- Patients are scheduled for follow-up visits at 3, 6, 9, and 12 months after therapy completion

Regenerative endodontic procedures is defined as biologically based procedures designed to replace damaged structures such as dentin, root structures, and cells of the pulp-dentin complex. This new treatment modality aims to promote normal function of the pulp. It has become an alternative to heal apical periodontitis. Regenerative endodontics is the extension of root canal therapy. Conventional root canal therapy cleans and fills the pulp chamber with biologically inert material after destruction of the pulp due to dental caries, congenital deformity or trauma. Regenerative endodontics instead seeks to replace live tissue in the pulp chamber. The ultimate goal of regenerative endodontic procedures is to regenerate the tissues and the normal function of the dentin-pulp complex.

Before this treatment modality is introduced, apexification procedures using either immediate placement of mineral trioxide aggregate apical plug or long term-calcium hydroxide treatment were traditionally used to treat immature permanent tooth. Although these treatments often resolve the signs and symptoms of pathosis, they provide little to no benefit for continued root development. Further root growth, normal pulpal nociception and immune defense are impeded in the procedure of apexification.

Regenerative endodontics in 10-year-old with necrotic pulp and incomplete root formation (left) then 1 year after treatment. Buccal aspect of apex (blue arrow), palatal aspect of apex (red arrow) and line of initial root formation (green line)

To replace live tissue, either the existing cells of the body are stimulated to regrow the tissue native to the area or bioactive substances inserted in the pulp chamber. These include stem cell therapy, growth factors, morphogens, tissue scaffolds and biologically active delivery systems.

Closely related to the field of regenerative endodontics, are the clinical procedures apexification and apexogenesis. When the dental pulp of a developing adult tooth dies, root formation is halted leaving an open tooth apex. Attempting to complete root canal on a tooth with an open apex is technically difficult and the long-term prognosis for the tooth is poor.

Apexogenesis, (which can be used when the pulp is injured but not necrotic) leaves the apical one-third of the dental pulp in the tooth which allows the root to complete formation. Apexification, stimulates cells in the periapical area of the tooth to form a dentin-like substance over the apex. Both improve the long-term prognosis for a forming tooth over root canal alone.

Necrotic pulp and open apex can be revitalized with platelet rich fibrin.

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