Periodontal regeneration with stem cells-seeded collagen-hydroxyapatite scaffold

Abstract

Re-establishing compromised periodontium to its original structure, properties and function is demanding, but also challenging, for successful orthodontic treatment. In this study, the periodontal regeneration capability of collagenhydroxyapatite scaffolds, seeded with bone marrow stem cells, was investigated in a canine labial alveolar bone defect model. Bone marrow stem cells were isolated, expanded and characterized. Porous collagen-hydroxyapatite scaffold and cross-linked collagen-hydroxyapatite scaffold were prepared. Attachment, migration, proliferation and morphology of bone marrow stem cells, co-cultured with porous collagen-hydroxyapatite or cross-linked collagen-hydroxyapatite, were evaluated in vitro. The periodontal regeneration capability of collagen-hydroxyapatite scaffold with or without bone marrow stem cells was tested in six beagle dogs, with each dog carrying one sham-operated site as healthy control, and three labial alveolar bone defects untreated to allow natural healing, treated with bone marrow stem cells -collagenhydroxyapatite scaffold implant or collagen-hydroxyapatite scaffold implant, respectively. Animals were euthanized at 3 and 6 months (3 animals per group) after implantation and the resected maxillary and mandibular segments were examined using micro-computed tomography scan, H&E staining, Masson's staining and histometric evaluation. Bone marrow stem cells were successfully isolated and demonstrated self-renewal and multi-potency in vitro. The porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite had average pore sizes of 415 AE 20 mm and 203 AE 18 mm and porosity of 69 AE 0.5% and 50 AE 0.2%, respectively. The attachment, proliferation and migration of bone marrow stem cells were satisfactory on both porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite scaffolds. Implantation of bone marrow stem cells -collagen-hydroxyapatite or collagen-hydroxyapatite scaffold in beagle dogs with experimental periodontal defects resulted in significantly enhanced periodontal regeneration characterized by formation of new bone, periodontal ligament and cementum, compared with the untreated defects, as evidenced by histological and micro-computed tomography examinations. The prepared collagen-hydroxyapatite scaffolds possess favorable bio-compatibility. The bone marrow stem cells -collagen-hydroxyapatite and collagen-hydroxyapatite scaffold -induced periodontal regeneration, with no aberrant events complicating the regenerative process. Further research is necessary to improve the bone marrow stem cells behavior in collagen-hydroxyapatite scaffolds after implantation.

Concise Review: Periodontal Tissue Regeneration Using Stem Cells: Strategies and Translational Considerations

“…In many cases, stem cell sheets are transplanted into the damaged periodontium with bone substitutes, such as hydroxyapatite/tricalcium phosphate (TCP; e.g., see ), bovine bone (e.g., see ), synthetic hydrogels (e.g., see ), and their composites (e.g., see ), to increase the stability of the cells within the defect (reviewed in ).…”

Hydroxyapatite–polymer biocomposites for bone regeneration: A review of current trends

“…Col/HA scaffolds loaded with human mesenchymal stem cells induced their differentiation without the requirement of any specific growth factors, making Col/HA biocomposites good option for delivering biomolecules, drugs, and growth factors . The potential of Col/HA biocomposites has been observed on implant coatings and dental restorations, and products such as Collagraft is commercially available …”

Effect of metformin on human periodontal ligament stem cells cultured with polydopamine‐templated hydroxyapatite

“…Tissue‐engineered regeneration is believed to be an ideal approach for restoration of bone defects in the oral cavity. This approach uses scaffolds, either alone or in combination with growth factor, cell, and/or gene delivery, and has the potential to manage bone loss and increase clinical options for controllable regeneration of periodontal osseous tissues . In our previous study, polydopamine‐templated hydroxyapatite (tHA), a type of biomimetic nano‐hydroxyapatite, was synthesized by employing polydopamine as a template under weak alkaline conditions; here, the catechol moiety of polydopamine strongly chelates Ca 2+ ions and forms hydrogen bonds with protonated and H 2 O on the surface of the mineral .…”