Efficient bone regeneration of BMP9-stimulated human periodontal ligament stem cells (hPDLSCs) in decellularized bone matrix (DBM) constructs to model maxillofacial intrabony defect repair

Abstract

Background BMP9-stimulated DPSCs, SCAPs and PDLSCs are effective candidates for repairing maxillofacial bone defects in tissue engineering, while the most suitable seed cell source among these three hDMSCs and the optimal combination of most suitable type of hDMSCs and BMP9 have rarely been explored. Moreover, the orthotopic maxillofacial bone defect model should be valuable but laborious and time-consuming to evaluate various candidates for bone regeneration. Thus, inspired from the maxillofacial bone defects and the traditional in vivo ectopic systems, we developed an intrabony defect repair model to recapitulate the healing events of orthotopic maxillofacial bone defect repair and further explore the optimized combinations of most suitable hDMSCs and BMP9 for bone defect repair based on this modified ectopic system. Methods Intrabony defect repair model was developed by using decellularized bone matrix (DBM) constructs prepared from the cancellous part of porcine lumbar vertebral body. We implanted DBM constructs subcutaneously on the flank of each male NU/NU athymic nude mouse, followed by directly injecting the cell suspension of different combinations of hDMSCs and BMP9 into the central hollow area of the constructs 7 days later. Then, the quality of the bony mass, including bone volume fraction (BV/TV), radiographic density (in Hounsfield units (HU)) and the height of newly formed bone, was measured by micro-CT. Furthermore, the H&E staining and immunohistochemical staining were performed to exam new bone and new blood vessel formation in DBM constructs. Results BMP9-stimulated periodontal ligament stem cells (PDLSCs) exhibited the most effective bone regeneration among the three types of hDMSCs in DBM constructs. Furthermore, an optimal dose of PDLSCs with a specific extent of BMP9 stimulation was confirmed for efficacious new bone and new blood vessel formation in DBM constructs. Conclusions The reported intrabony defect repair model can be used to identify optimized combinations of suitable seed cells and biological factors for bone defect repair and subsequent development of efficacious bone tissue engineering therapies.

Research on 3D-Printed FGF2-PLGA/PLGA-nHA-BMP9 Biphasic Scaffolds with Sequential Delivery of FGF2 and BMP9 in Promoting Periodontal Ligament Cells’ Proliferation and Differentiation

“…The application of 3D printing technologyin fabricating personalized scaffolds from seed cells, polymer materials, and growth factors for periodontal tissue regeneration is garnering increased focus. This regeneration encompasses the renewal of the periodontal ligament and alveolar bone, entailing complex processes such as cell chemotaxis, adhesion, proliferation, and differentiation, each requiring distinct regulatory factors at various stages and tissues [11]. Extensive research [12,13] has validated that FGF2 and BMP9 significantly enhance the proliferation and differentiation of periodontal ligament stem cells, thereby facilitating periodontal tissue regeneration.…”

Roles of human periodontal ligament stem cells in osteogenesis and inflammation in periodontitis models: effect of 1α,25-dihydroxyvitamin D 3

“…As one of the most promising types of seed cells in periodontal tissue regeneration, human periodontal ligament stem cells (hPDLSCs) are mesenchymal stem cells that have the self-renewal and multidirectional differentiation abilities. Their osteogenic differentiation ability may represent a breakthrough in the treatment of periodontal supporting tissue defects, as demonstrated in many studies [3][4][5] . However, some crucial issues including the in uence of in ammation on hPDLSCs, growth-promoting factors of hPDLSCs, and host state factors remain unknown in the complex periodontal microenvironment.…”

Superoxide dismutase 2 scavenges ROS to promote osteogenic differentiation of human periodontal ligament stem cells by regulating Smad3 in alveolar bone‐defective rats

“…5,6 Periodontal ligament stem cells (PDLSCs) are considered well-suited for alveolar bone regeneration. 7 PDLSCs have demonstrated proliferative and regenerative capacities in multiple studies, [8][9][10][11] making them an ideal source of stem cells for alveolar bone regeneration.…”