Fundamentals and Translational Applications of Stem Cells and Biomaterials in Dental, Oral and Craniofacial Regenerative Medicine.

Regenerative dental medicine continuously expands to improve treatments for prevalent clinical problems in dental and oral medicine. Stem cell based translational opportunities include regenerative therapies for tooth restoration, root canal therapy, and inflammatory processes (e.g., periodontitis). The potential of regenerative approaches relies on the biological properties of dental stem cells. These and other multipotent somatic mesenchymal stem cell (MSC) types can in principle be applied as either autologous or allogeneic sources in dental procedures. Dental stem cells have distinct developmental origins and biological markers that determine their translational utility. Dental regenerative medicine is supported by mechanistic knowledge of the molecular pathways that regulate dental stem cell growth and differentiation. Cell fate determination and lineage progression of dental stem cells is regulated by multiple cell signaling pathways (e.g., WNTs, BMPs) and epigenetic mechanisms, including DNA modifications, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs). This review also considers a broad range of novel approaches in which stem cells are applied in combination with biopolymers, ceramics, and composite materials, as well as small molecules (agonistic or anti-agonistic ligands) and natural compounds. Materials that mimic the microenvironment of the stem cell niche are also presented. Promising concepts in bone and dental tissue engineering continue to drive innovation in dental and non-dental restorative procedures.

The activin/BMP-2 chimera AB204 promotes periodontal tissue regeneration in a buccal dehiscence model: a pilot study.

PURPOSE: A combination of activin and bone morphogenetic protein-2 (BMP-2), termed AB204, has been shown to improve osteogenic potential with fewer side effects than BMP-2 alone. This study was performed to evaluate the effect of AB204 on periodontal tissue regeneration in a dog buccal dehiscence model. METHODS: Buccal dehiscence defects were created on the maxillary premolars (P1, P2, and P3) of 6 mongrel dogs. After 5 weeks, the dogs were randomly assigned to 1 of 3 groups: the control, collagen matrix (CM), and CM/AB204 groups. Grafting procedures were then performed. The dogs were sacrificed 8 weeks after the grafting procedure, and volumetric and histological analyses were conducted. RESULTS: The thickness of the buccal gingiva in the CM/AB204 group was greater than those in the other groups at 2 weeks (P<0.05). The ridge width in the AB204/CM group exceeded the width in the other groups at 4 and 8 weeks; however, the difference was not statistically significant. Histological analysis revealed that the CM/AB204 group demonstrated the formation of new bone surrounded by newly formed periodontal ligament and cementum (P=0.035). CONCLUSIONS: The combined application of CM and AB204 shows promise in facilitating the regeneration of periodontal attachment, including the formation of new bone, cementum, and periodontal ligament.

Bone regeneration using activin A/BMP2 chimera (AB204) with collagen membrane in rats with calvarial defects.

PURPOSE: Collagen has long been recognized as an excellent carrier for growth factors, and membrane-type collagen has been widely applied in dentistry for guided bone regeneration. This study was conducted to examine the effects of an activin A/BMP2 chimera (AB204) combined with a collagen membrane (CM) on bone repair in a rat calvarial defect model. METHODS: A unilateral calvarial defect measuring 5.0 mm was surgically created in 32 Sprague-Dawley rats. The rats were then randomly assigned to 1 of 4 groups, each consisting of 8 animals: control (untreated), CM (treated with a CM only), CM/bone morphogenetic protein 2 (BMP2) (treated with a CM and 1.0 µg of BMP2), and CM/AB204 (treated with a CM and 1.0 µg of AB204). Bone regeneration was evaluated using micro-computed tomography (CT) and histological analysis at 2 and 4 weeks following surgery. RESULTS: Micro-CT analysis revealed that bone formation in the CM/BMP2 and CM/AB204 groups was superior to that observed in the control and CM groups at both 2 and 4 weeks postoperatively. BMP2 induced greater bone regeneration than AB204 at 2 weeks; however, AB204 resulted in a greater bone volume at 4 weeks, achieving the highest values recorded. No significant differences were found between the CM/BMP2 and CM/AB204 groups at either time point (P>0.05). On histological examination, new bone formation was evident in both CM/BMP2 and CM/AB204 groups. CONCLUSIONS: Within the limitations of this study, the findings indicate that AB204 may enhance osteogenic potential when used in combination with CM for bone regeneration.

Effectiveness of a collagen matrix seal and xenograft in alveolar ridge preservation: an experimental study in dogs.

Majority of previous studies on alveolar ridge preservation (ARP) used collagen membranes as barrier membranes, and further evidence for ARP in dehiscent extraction sockets with a deproteinized bovine bone mineral (DBBM) and matrix is needed. The aim of this study is to assess the impact of non-cross linked collagen membranes (membrane) and crosslinked collagen matrices (matrix) on ARP using DBBM in extraction sockets with buccal dehiscence. In six mongrel dogs, the mesial roots of three mandibular premolars (P2, P3, and P4) were extracted 1 month after dehiscence defect induction. Two experimental groups were randomly assigned: (1) DBBM with a membrane (DBBM/membrane group) and (2) DBBM with a matrix (DBBM/matrix group). Three-dimensional (3D) volumetric, microcomputed tomography (µCT), and histologic analyses were performed to assess the ridge preservation. Both groups were effective to maintain the ridge width (p > 0.05), and the DBBM/matrix group showed more favorable soft tissue regeneration and bone quality in the histological analysis (p = 0.05). Based on these results, DBBM/matrix could be better choice for ARP in cases of buccal dehiscence defects.

Alveolar Ridge Preservation Using a Collagenated Xenograft: A Randomized Clinical Trial.

OBJECTIVES: This study sought to evaluate the efficacy of cancellous bovine bone mineral granules and 10% porcine collagen (deproteinized bovine bone mineral with collagen [DBBM-C]; (OCS-B Collagen® [Straumann XenoFlex], NIBEC, Korea) in a mouldable block form, with or without socket seal, using autogenous free gingival graft (FGG). METHODS: Fifty-four patients were included and randomly assigned to one of three groups: (1) spontaneous healing (control group), (2) alveolar ridge preservation (ARP) using DBBM-C (DBBM-C group), and (3) ARP employing DBBM-C sealed with FGG (DBBM-C/FGG group). Bone biopsy and implant fixture placement were performed 180 days after ARP. Cone-beam computed tomography, histological analysis, implant stability, and three-dimensional volumetric analysis were conducted. RESULTS: Of the 54 patients, 4 dropped out owing to loss of follow-up and osseointegration failure. The changes in alveolar bone during follow-up were not significantly different. Between 84- and 180-day postextraction, the volume of the DBBM-C and DBBM-C/FGG groups was maintained at 3 mm below the alveolar ridge crest (0.72 ± 0.80 mm, 6.05 ± 6.69%), whereas the volume in the control group decreased (-0.37 ± 1.31 mm, -2.10% ± 8.37%) (P = .026). The DBBM-C/FGG group exhibited less horizontal ridge resorption at 1 mm below the alveolar crest (-9.19 ± 5.09 mm, -73.67% ± 32.53%) between preextraction and 84 days postextraction (P = .049). In all groups, the implant stability quotient remained above 70. CONCLUSIONS: Within the limitations of this study, both ARP using DBBM-C with and without socket sealing effectively preserved the width dimension of the alveolar ridge, with no significant difference in alveolar bone resorption. However, socket sealing appeared to enhance the stability of the bone graft and bone quality. CLINICAL RELEVANCE: The use of DBBM-C for ARP seems to aid in volume maintenance as compared with spontaneous healing. Gingival sealing with an FGG can help maintain the width of the alveolar ridge. This clinical trial was not registered prior to participant recruitment and randomization. This study was registered at WHO ICTRP (https://trialsearch.who.int/Trial2.aspx?TrialID=KCT0008266).

Bone-targeted lipoplex-loaded three-dimensional bioprinting bilayer scaffold enhanced bone regeneration.

Clinical bone-morphogenetic protein 2 (BMP2) treatment for bone regeneration, often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems, necessitates research into improved biomaterials for better BMP2 stability and retention. To tackle this challenge, we introduced a groundbreaking bone-targeted, lipoplex-loaded, three-dimensional bioprinted bilayer scaffold, termed the polycaprolactone-bioink-nanoparticle (PBN) scaffold, aimed at boosting bone regeneration. We encapsulated BMP2 within the fibroin nanoparticle based lipoplex (Fibroplex) and functionalized it with DSS6 for bone tissue-specific targeting. 3D printing technology enables customized, porous PCL scaffolds for bone healing and soft tissue growth, with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex, shown to support effective nutrient exchange and cell growth at specific pore sizes. The PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue, a finding validated by in vitro osteogenic differentiation assays. The PBN scaffold was evaluated for critical calvarial defects, focusing on sustained BMP2 delivery, prevention of soft tissue cell infiltration and controlled fiber membrane pore size in vivo. The PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge, promoting osteogenic differentiation and bone regeneration in a calvarial defect animal. Our findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation, thereby reducing the risk of heterotopic ossification.