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).

Clinical efficacy of Vestibular Incision Subperiosteal Tunnel Access (VISTA) for treatment of multiple gingival recession defects: a systematic review, meta-analysis and meta-regression.

OBJECTIVES: This study investigated the efficacy of Vestibular Incision Subperiosteal Tunnel Access (VISTA) compared to other methods for treating multiple adjacent gingival recessions (MAGRs) through a systematic review and meta-analysis. MATERIALS AND METHODS: A systematic literature search was performed through June 2023, to identify clinical trials investigating VISTA for root coverage on MAGRs. A meta-analysis with meta-regression model was employed on the primary outcomes of mean and complete root coverages (MRC, CRC), comparing VISTA with other techniques. Clinical efficacy of various graft materials was assessed. RESULTS: Fourteen studies were included, 8 of which met the criteria for quantitative assessment. The cumulative MRC (88.15% ± 20.79%) and CRC (67.85% ± 21.72%) of VISTA were significantly higher compared to the tunneling technique (SMD = 0.83 (95% CI [0.36, 1.30], p < 0.01). The baseline recession depth showed a negative correlation with CRC, whereas baseline keratinized gingiva width exhibited a positive correlation with this outcome. CONCLUSIONS: The VISTA technique, particularly with acellular dermal matrix (ADM) or connective tissue graft (CTG) materials, offers superior outcomes compared to the tunneling technique. The capacity of platelet-rich fibrin (PRF) to substitute for connective tissue graft (CTG) in VISTA-root coverage was noteworthy, provided there is adequate keratinized tissue width. CLINICAL RELEVANCE: VISTA in concert with acellular dermal matrix or CTG resulted in improved root coverage, surpassing the outcomes achieved through tunneling. PRF emerged as a viable alternative to CTG, when used in conjunction with VISTA, demonstrating comparable mean root coverage. This is particularly evident in situations where sufficient keratinized gingiva is available and when patient comfort is taken into consideration.

Fibrin immobilization vestibular extension (FIVE): A case series.

AIMS: The objective of the present case series is to report on the rationale, surgical technique and outcome of a protocol for peri-implant mucosal phenotype modification therapy, referred to as "fibrin immobilization vestibular extension (FIVE)". MATERIAL AND METHODS: The protocol utilized entailed apical positioning and stabilization of peri-implant flap with modular screws. The screws were also used for the immobilization of solid matrix platelet-rich fibrin to fill the gap created between apically positioned flap and the crestal margin of the flap. RESULTS: A total of 30 patients (12 male, 18 females) with 93 implants were treated with FIVE protocol for various indications, including for vestibular extension following alveolar ridge augmentation (N = 6), preprosthetic (N = 9), postprosthetic (N = 2), and peri-implantitis (N = 13). The keratinized mucosal width preoperatively was 1.67 mm with 95% confidence interval [CI] (1.46, 1.88). Immediately following FIVE surgery, the vestibule was extended to 9.10 with 95% CI (8.44, 9.76). At 3 months, 4.9 mm (95% CI: 4.5-5.2 mm) of peri-implant keratinized mucosal width was present. The keratinized mucosal width remained relatively stable thereafter and was 4.0 mm (95% CI: 3.5-4.5 mm) at 3 years post-FIVE surgery. When overall group means across all time points were analyzed, maxilla had mean of 6.1 mm (95% CI: 5.8-6.5) versus mandible exhibited mean of 5.1 mm (95% CI: 4.6-5.6 mm). The mean of maxilla was significantly higher than that of the mandible (p < 0.0001) across all time points. Treatment of peri-implantitis with FIVE lead to significant pocket reduction and wide band of keratinized mucosa. Seven of 38 implants in 3 of 13 peri-implantitis patients were removed due to advanced peri-implantitis. DISCUSSION: The present case series provides proof-of-principle data for efficacy of FIVE for peri-implant phenotype modification therapy that generated attached keratinized mucosa in a variety of applications. This protocol provides an alternative to procedures involving harvesting of autogenous mucosal graft.

A multifunctional fusion peptide for tethering to hydroxyapatite and selective capture of bone morphogenetic protein from extracellular milieu.

PURPOSE: The present study sought to design a multi-functional fusion peptide with hydroxyapatite (HA) binding domain (HABD) and heparin binding domain (HBD). METHODS: The 74 amino acid fusion peptide contained N-terminus of the fibrinogen ß chain (ß 15-66), double G4S-linker and 12 residues with HA affinity. This construct was designed, synthesized and cloned into pET21a(+) vector and expressed in E. coli. RESULTS: HABD facilitated purification of the fusion peptide by HA affinity chromatography. Kinetic peptide binding and release on HA scaffold showed sustained release of peptide for up to 16 days. Competitive ELISA and intrinsic fluorescence assays were applied to determine HBD affinity to bone morphogenetic protein-2 (BMP-2). The disassociation rate constant (Kd ) for HBD and rhBMP-2 was approximately 9.2-12 nM. CONCLUSION: The fusion peptide developed in the present study, allowed for streamlined purification on HA affinity chromatography, as well as sustained release from HA scaffold, attributed to its HABD. HBD mediated binding to BMP-2, which may be potentially useful for bone repair. Additional studies, including in vivo investigation will be required to assess the efficacy of the fusion peptide in bone tissue engineering.

Buccal fat pad-derived stem cells with anorganic bovine bone mineral scaffold for augmentation of atrophic posterior mandible: An exploratory prospective clinical study.

BACKGROUND: Application of adipose-derived stem cells originated from buccal fat pad (BFP) can simplify surgical procedures and diminish clinical risks compared to large autograft harvesting. PURPOSE: This study sought to evaluate and compare the efficacy of buccal fat pad-derived stem cells (BFPSCs) in combination with anorganic bovine bone mineral (ABBM) for vertical and horizontal augmentation of atrophic posterior mandibles. MATERIALS AND METHODS: Fourteen patients with atrophic posterior mandible were elected for this prospective exploratory study. BFP (3-5 mL) was harvested and BFPSCs were isolated and combined with ABBM at 50% ratio. The vertical and horizontal alveolar deficiencies were augmented by 50% mixture of ABBM with either BFPSCs (group 1) or particulated autologous bone (group 2). Titanium mesh was contoured to the desired 3D shape of the alveolar ridge and fixated to the host sites over the graft material of the two groups. At first, the amount of new bone areas was calculated by quantitative analysis of cone beam computed tomography (CBCT) images that were taken 6 months postoperatively according to regenerative techniques (group 1 vs group 2 without considering the type of bone defects). Second, these amounts were calculated in each group based on the type of defects. RESULTS: Quantitative analysis of CBCT images revealed the areas of new bone formation were 169.5 ± 5.90 mm2 and 166.75 ± 10.05 mm2 in groups 1 and 2, respectively. The area of new bone formation for vertical defects were 164.91 ± 3.74 mm2 and 169.36 ± 12.09 mm2 in groups 1 and 2, respectively. The area of new bone formation for horizontal deficiencies were 170.51 ± 4.54 mm2 and 166.98 ± 9.36 mm2 in groups 1 and 2, respectively. There were no statistically significant differences between the two groups in any of the pair-wise comparisons (P > 0.05). CONCLUSIONS: The findings of the present study demonstrated lack of difference in bone volume formation between BFPSCs and autologous particulate bone in combination with ABBM. If confirmed by future large-scale clinical trial, BFPSCs may provide an alternative to autogenous bone for reconstruction of alveolar ridge defects.

Vestibular Incision Subperiosteal Tunnel Access (VISTA) for Surgically Facilitated Orthodontic Therapy (SFOT).

Surgically Facilitated Orthodontic Therapy (SFOT) in combination with bone augmentation and the placement of anchorage devices installed into bone have been used to accelerate and facilitate orthodontic treatment. This is usually performed after flap surgery, which is associated with moderate morbidity, as well as possible negative sequale such as gingival recession. The present case report illustrates the clinical benefits of vestibular incision subperiosteal tunnel access (VISTA) for SFOT, and tissue augmentation to facilitate orthodontic therapy. VISTA entails making vertical incision(s) in the vestibule followed by subperiosteal elevation of tunnels to provide direct access to the facial alveolar bone. Unlike previously reported vestibular access surgical procedures, VISTA allows for wider elevation of an access tunnel for clear visual and surgical access to perform careful inter-radicular corticotomy. The present report describes VISTA for corticotomy surgery (anterior mandible and maxillary teeth) in combination with the placement of titanium fixation devices and bone augmentation to facilitate orthodontic treatment of an adult female with borderline Class II Division 1 malocclusion, with excessive overjet and deepbite. In view of the fact that VISTA does not require surface incisions in the gingival margins or papillae, it potentially minimizes gingival recession that sometimes accompanies flap surgery.

Treatment of multiple recession defects with vestibular incision subperiosteal tunnel access (VISTA): A retrospective pilot study utilizing digital analysis.

OBJECTIVE: To examine the correlation between initial site-specific characteristics of patients with multiple gingival recession defects and the outcome of root coverage therapy. MATERIALS AND METHODS: Pretherapy and post-therapy study models of 21 patients (154 teeth) with multiple gingival recession defects, treated with Vestibular Incision Subperiosteal Tunnel Access (VISTA), were optically scanned. Three-dimensional analysis of superimposed preoperative and postoperative images was performed. Linear and surface root coverage were calculated and correlated to various clinical and/or anatomical parameters. A multilevel statistical analysis was conducted, adjusting for the correlation among multiple observations. RESULTS: The mean percentages of linear root coverage were 96.2 ± 13.1% and 84.3 ± 14.4% for Miller Class I/II and Class III recessions, respectively. The mean percentages of root surface area coverage were 92.1 ± 12.0% and 78.6 ± 15.7% for Miller Class I/II and III defects, respectively. Root prominence, initial recession width and posterior tooth type were negatively correlated with linear and root surface area coverage. Initial recession depth was negatively correlated with root surface area coverage. Initial gingival margin thickness was positively associated with both linear and root surface area coverage. CONCLUSION: The results of the present study identified important positive and negative site-specific characteristics that may have utility in predicting the outcome of root coverage. CLINICAL SIGNIFICANCE: This study used sensitive 3-dimensional digital analysis tools to examine the correlation between initial site-specific characteristics of patients with multiple gingival recession defects and the outcome of periodontal root coverage therapy. Results demonstrated that initial root prominence, loss of interdental tissue (Miller Class III), molar tooth type, initial recession depth and width were negatively correlated with the outcome of periodontal root coverage achieved. Conversely, initial gingival margin thickness was associated with increased percentage of root coverage. These site-specific characteristics may serve as important risk indicators to predict the outcome of root coverage procedure.

Histological and Histomorphometric Response to SocketKAP™ and SocketKAGE™ Used for Ridge Preservation and Repair: Results From a Randomized Controlled Clinical Trial.

PURPOSE: This study investigated the histologic tissue response to SocketKAP and SocketKAGE as novel devices designed for ridge preservation. MATERIALS AND METHODS: This randomized controlled clinical trial recruited participants among patients who presented to a university dental clinic. The study protocol entailed randomization into 5 intervention groups after tooth extraction: unassisted healing of intact sockets (group A), SocketKAP (group B), anorganic bovine bone minerals (ABBM) plus SocketKAP (group C), unassisted healing of sockets with dehiscence (group D), and SocketKAGE plus ABBM plus SocketKAP (group E). The primary outcome variable was bone volume fraction of total volume (BV/TV). Secondary outcome variables were percentages of residual graft material (RG) and void volume (VV). One-way analysis of variance was run on BV/TV, RG, and VV based on the independent variable (treatment groups). RESULTS: Bone core samples were harvested from participants (N = 22) who presented for implant installation at 6 months after extraction. Sockets without biomaterial filler (groups A and B) showed more mature bone compared with grafted sockets. In groups in which sockets were filled with biomaterial (groups C and E), vital bone was observed in direct apposition to the graft particles. In group E, remnants of SocketKAGE were not readily discernable at 6 months. No substantial inflammatory infiltrate or other adverse histologic patterns were detected. Quantitative analysis showed a statistically significant difference in BV/TV between groups A and C (P = .028) and between groups A and E (P = .019). CONCLUSIONS: Histologic and histomorphometric results showed that the application of SocketKAP and SocketKAGE did not interfere with wound healing of extraction sockets. In agreement with previous reports, the percentage of BV/TV within sites with ABBM was smaller than within sites without biomaterial. The favorable histologic response to SocketKAP and SocketKAGE observed in the present study provided additional insights to the authors' previous studies showing the benefits of these devices in decreasing postextraction dimensional alterations of alveolar bone and tissue contour.

Antibody Administration for Bone Tissue Engineering: A Systematic Review.

BACKGROUND: Currently, antibodies are progressively applied in medicine for different purposes, including diagnostic and therapeutic indications. Over twenty monoclonal antibodies utilized for many therapeutic reasons from therapy of cancers, immune disorders, and osteoporosis to localized bony defects. In addition, therapeutic antibodies represented various findings in bone tissue engineering. OBJECTIVES: The current study aims to systematically review the available literature on antibody assisted bone regeneration in animal models. METHODS: A through electronic search was conducted from January 1992 to June 2017 limited to English language publications on administrations of antibodies for bone regeneration. Data extraction was ere performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Twenty studies were selected and analyzed in this systematic review. Among these studies, six articles reported in vitro results in addition to in vivo evaluations. The data is tabulated according to the route of administrations as locally administrated antibody which includes anti-bone morphogenetic protein 2 (anti-BMP2) and systemic administrated antibodies, which include anti-sclerostin and anti- Dickkopf-1 (DKK1). Data are summarized and reported by the following variables: Type of study, types of cells for in vitro investigations, types of animal models and defects characteristics, types of scaffolds used in the defect site, duration of follow-ups; and outcomes of assessments. CONCLUSIONS: A novel approach of administration of antibodies demonstrated promising results for bone tissue engineering. However, more investigations, particularly in larger animals, are required for their further possible clinical administration.

Human Gingiva-Derived Mesenchymal Stem Cells Ameliorate Streptozoticin-induced T1DM in mice via Suppression of T effector cells and Up-regulating Treg Subsets.

There is yet no cure for type 1 diabetes (T1DM) so far. A significant body of evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) showed great potential in controlling T1DM. But there exists much difficulty in using BMSCs as a clinical therapy. We here test whether a new population of mesenchymal stem cells from human gingiva (GMSCs), which has many advantages over BMSCs, can delay or prevent progress of T1DM. GMSCs were adoptively transferred to multiple low-dose streptozotocin (STZ)-induced T1DM. Blood glucose levels and disease severities were analyzed. T cells subsets in blood, spleen and lymph nodes were detected dynamically by flow cytometry. GMSC distribution was dynamically analyzed. We found that infusion of GMSCs but not fibroblast cells significantly controlled blood glucose levels, delayed diabetes onset, ameliorated pathology scores in pancreas, and down-regulated production of IL-17 and IFN-γ in CD4+ and CD8+ T cells in spleens, pancreatic lymph nodes (pLN) and other lymph nodes. GMSCs also up-regulated the levels of CD4+ Treg induced in the periphery. Mechanismly, GMSCs could migrate to pancreas and local lymph node and function through CD39/CD73 pathway to regulate effector T cells. Thus, GMSCs show a potential promise in treating T1DM in the clinic.

Hydrogel elasticity and microarchitecture regulate dental-derived mesenchymal stem cell-host immune system cross-talk.

The host immune system (T-lymphocytes and their pro-inflammatory cytokines) has been shown to compromise bone regeneration ability of mesenchymal stem cells (MSCs). We have recently shown that hydrogel, used as an encapsulating biomaterial affects the cross-talk among host immune cells and MSCs. However, the role of hydrogel elasticity and porosity in regulation of cross-talk between dental-derived MSCs and immune cells is unclear. In this study, we demonstrate that the modulus of elasticity and porosity of the scaffold influence T-lymphocyte-dental MSC interplay by regulating the penetration of inflammatory T cells and their cytokines. Moreover, we demonstrated that alginate hydrogels with different elasticity and microporous structure can regulate the viability and determine the fate of the encapsulated MSCs through modulation of NF-kB pathway. Our in vivo data show that alginate hydrogels with smaller pores and higher elasticity could prevent pro-inflammatory cytokine-induced MSC apoptosis by down-regulating the Caspase-3- and 8- associated proapoptotic cascades, leading to higher amounts of ectopic bone regeneration. Additionally, dental-derived MSCs encapsulated in hydrogel with higher elasticity exhibited lower expression levels of NF-kB p65 and Cox-2 in vivo. Taken together, our findings demonstrate that the mechanical characteristics and microarchitecture of the microenvironment encapsulating MSCs, in addition to presence of T-lymphocytes and their pro-inflammatory cytokines, affect the fate of encapsulated dental-derived MSCs. STATEMENT OF SIGNIFICANCE: In this study, we demonstrate that alginate hydrogel regulates the viability and the fate of the encapsulated dental-derived MSCs through modulation of NF-kB pathway. Alginate hydrogels with smaller pores and higher elasticity prevent pro-inflammatory cytokine-induced MSC apoptosis by down-regulating the Caspase-3- and 8- associated proapoptotic cascade, leading to higher amounts of ectopic bone regeneration. MSCs encapsulated in hydrogel with higher elasticity exhibited lower expression levels of NF-kB p65 and Cox-2 in vivo. These findings confirm that the fate of encapsulated MSCs are affected by the stiffness and microarchitecture of the encapsulating hydrogel biomaterial, as well as presence of T-lymphocytes/pro-inflammatory cytokines providing evidence concerning material science, stem cell biology, the molecular mechanism of dental-derived MSC-associated therapies, and the potential clinical therapeutic impact of MSCs.

Human Gingiva-Derived Mesenchymal Stem Cells Inhibit Xeno-Graft-versus-Host Disease via CD39-CD73-Adenosine and IDO Signals.

Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the therapeutic and translational potential of this approach for applications in human disease. We found that GMSCs potently suppressed the proliferation of PBMC and T cells in vitro. Co-transfer of GMSC with human PBMC significantly suppressed human cell engraftment and markedly prolonged the mouse survival. Moreover, we demonstrated that GMSCs inhibited human PBMC-initiated xenogenic responses via CD39/CD73/adenosine and IDO signals. These findings suggest the potential for GMSCs to suppress human immune responses in immune system-mediated diseases, offering a potential clinical option to be used for modulating GVHD and autoimmune diseases.

Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors.

Repair and regeneration of muscle tissue following traumatic injuries or muscle diseases often presents a challenging clinical situation. If a significant amount of tissue is lost the native regenerative potential of skeletal muscle will not be able to grow to fill the defect site completely. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material, present an advantageous alternative therapeutic option for muscle tissue engineering in comparison to current treatment modalities available. To date, there has been no report on application of gingival mesenchymal stem cells (GMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of the current study were to develop an injectable 3D RGD-coupled alginate scaffold with multiple growth factor delivery capacity for encapsulating GMSCs, and to evaluate the capacity of encapsulated GMSCs to differentiate into myogenic tissue in vitro and in vivo where encapsulated GMSCs were transplanted subcutaneously into immunocompromised mice. The results demonstrate that after 4 weeks of differentiation in vitro, GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited muscle cell-like morphology with high levels of mRNA expression for gene markers related to muscle regeneration (MyoD, Myf5, and MyoG) via qPCR measurement. Our quantitative PCR analyzes revealed that the stiffness of the RGD-coupled alginate regulates the myogenic differentiation of encapsulated GMSCs. Histological and immunohistochemical/fluorescence staining for protein markers specific for myogenic tissue confirmed muscle regeneration in subcutaneous transplantation in our in vivo animal model. GMSCs showed significantly greater capacity for myogenic regeneration in comparison to hBMMSCs (p < 0.05). Altogether, our findings confirmed that GMSCs encapsulated in RGD-modified alginate hydrogel with multiple growth factor delivery capacity is a promising candidate for muscle tissue engineering.

An open randomized controlled clinical trial to evaluate ridge preservation and repair using SocketKAP(™) and SocketKAGE(™) : part 1-three-dimensional volumetric soft tissue analysis of study casts.

OBJECTIVES: The aims of this study were to evaluate (i) the efficacy of ridge preservation and repair involving SocketKAP(™) and SocketKAGE(™) devices following tooth removal; and (ii) ridge contour changes at 6 months post-extraction in intact sockets and sockets with dehiscence defects. MATERIAL AND METHODS: Thirty-six patients required a total of 61 teeth to be extracted. Five cohorts were established with groups A-C involving intact sockets and groups D and E involving facial dehiscence: (A) Negative Control; (B) SocketKAP(™) alone; (C) Anorganic Bovine Bone Mineral (ABBM) + SocketKAP(™) ; (D) Negative Control; and (E) ABBM + SocketKAP(™)  + SocketKAGE(™) . Preoperative CBCT and laser-scanned casts were obtained. Teeth segmented from preoperative CBCT were merged with study cast images to allow for digital removal of teeth from the casts. Volumetric measurements of ridge contour were performed. Images of preoperative and 6 months post-operative casts were superimposed to measure ridge contour changes. RESULTS: Post-extraction contour loss occurred in all sockets primarily in the crestal 3 mm but was also detected up to 6 mm from alveolar crest. For intact sockets, SocketKAP(™) or SocketKAP(™)  + ABBM interventions led to greater percentages of remaining ridge contour when compared to controls. A significant difference favoring SocketKAP(™)  + SocketKAGE(™)  + ABBM treatment was observed for sockets with facial dehiscence when compared to controls. CONCLUSION: SocketKAP(™) , with or without ABBM, significantly limited post-extraction ridge contour loss in intact sockets. In the absence of a group treated with only the SocketKAGE(™) , it is not possible to determine its efficacy, although the combination of SocketKAGE(™)  + SocketKAP(™)  + ABBM was effective in limiting post-extraction ridge contour loss in sockets with dehiscence defects.

An open randomized controlled clinical trial to evaluate ridge preservation and repair using SocketKAP(™) and SocketKAGE(™) : part 2 - three-dimensional alveolar bone volumetric analysis of CBCT imaging.

OBJECTIVES: The aims of this study were (i) to evaluate the efficacy of ridge preservation and repair procedures involving the application of SocketKAP(™) and SocketKAGE(™) devices following tooth removal and (ii) to evaluate alveolar bone volumetric changes at 6 months post-extraction in intact sockets or those with facial wall dehiscence defects using 3-dimensional pre- and postoperative CBCT data. MATERIALS AND METHODS: Thirty-six patients required 61 teeth extracted. Five cohorts were established: Group A: Intact Socket Negative Control Group B: Intact Socket + SocketKAP(™) Group C: Intact Socket Filled with Anorganic Bovine Bone Mineral (ABBM) + SocketKAP(™) Group D: Facial Dehiscence Socket Negative Control Group E: Facial Dehiscence Socket Filled with ABBM + SocketKAP(™) + SocketKAGE(™) . Preoperative CBCT scans were obtained followed by digital subtraction of the test teeth. At 6 months post-extraction, another CBCT scan was obtained. The pre- and postoperative scans were then superimposed, allowing highly accurate quantitative determination of the 3D volumetric alveolar bone volume changes from baseline through 6 months. RESULTS: Significant volumetric bone loss occurred in all sockets, localized mainly in the 0-3 mm zone apical to the ridge crest. For intact sockets, SocketKAP(™) + ABBM treatment led to a statistically significant greater percentage of remaining mineralized tissue volume when compared to negative control group. A significant difference favoring SocketKAP(™) + SocketKAGE(™) + ABBM treatment was observed for sockets with facial dehiscence defects compared to the negative control group. CONCLUSIONS: SocketKAP(™) , with ABBM, appears effective in limiting post-extraction volumetric bone loss in intact sockets, while SocketKAP(™) + SocketKAGE + ABBM appears effective in limiting post-extraction bone loss in sockets with dehiscence defects.

Gingival Mesenchymal Stem Cell (GMSC) Delivery System Based on RGD-Coupled Alginate Hydrogel with Antimicrobial Properties: A Novel Treatment Modality for Peri-Implantitis.

PURPOSE: Peri-implantitis is one of the most common inflammatory complications in dental implantology. Similar to periodontitis, in peri-implantitis, destructive inflammatory changes take place in the tissues surrounding a dental implant. Bacterial flora at the failing implant sites resemble the pathogens in periodontal disease and consist of Gram-negative anaerobic bacteria including Aggregatibacter actinomycetemcomitans (Aa). Here we demonstrate the effectiveness of a silver lactate (SL)-containing RGD-coupled alginate hydrogel scaffold as a promising stem cell delivery vehicle with antimicrobial properties. MATERIALS AND METHODS: Gingival mesenchymal stem cells (GMSCs) or human bone marrow mesenchymal stem cells (hBMMSCs) were encapsulated in SL-loaded alginate hydrogel microspheres. Stem cell viability, proliferation, and osteo-differentiation capacity were analyzed. RESULTS: Our results showed that SL exhibited antimicrobial properties against Aa in a dose-dependent manner, with 0.50 mg/ml showing the greatest antimicrobial properties while still maintaining cell viability. At this concentration, SL-containing alginate hydrogel was able to inhibit Aa growth on the surface of Ti discs and significantly reduce the bacterial load in Aa suspensions. Silver ions were effectively released from the SL-loaded alginate microspheres for up to 2 weeks. Osteogenic differentiation of GMSCs and hBMMSCs encapsulated in the SL-loaded alginate microspheres were confirmed by the intense mineral matrix deposition and high expression of osteogenesis-related genes. CONCLUSION: Taken together, our findings confirm that GMSCs encapsulated in RGD-modified alginate hydrogel containing SL show promise for bone tissue engineering with antimicrobial properties against Aa bacteria in vitro.

Pluronic F-127 hydrogel as a promising scaffold for encapsulation of dental-derived mesenchymal stem cells.

Dental-derived mesenchymal stem cells (MSCs) provide an advantageous therapeutic option for tissue engineering due to their high accessibility and bioavailability. However, delivering MSCs to defect sites while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated tissue regeneration. Here, we tested the osteogenic and adipogenic differentiation capacity of dental pulp stem cells (DPSCs) in a thermoreversible Pluronic F127 hydrogel scaffold encapsulation system in vitro. DPSCs were encapsulated in Pluronic (®) F-127 hydrogel and stem cell viability, proliferation and differentiation into adipogenic and osteogenic tissues were evaluated. The degradation profile and swelling kinetics of the hydrogel were also analyzed. Our results confirmed that Pluronic F-127 is a promising and non-toxic scaffold for encapsulation of DPSCs as well as control human bone marrow MSCs (hBMMSCs), yielding high stem cell viability and proliferation. Moreover, after 2 weeks of differentiation in vitro, DPSCs as well as hBMMSCs exhibited high levels of mRNA expression for osteogenic and adipogenic gene markers via PCR analysis. Our histochemical staining further confirmed the ability of Pluronic F-127 to direct the differentiation of these stem cells into osteogenic and adipogenic tissues. Furthermore, our results revealed that Pluronic F-127 has a dense tubular and reticular network morphology, which contributes to its high permeability and solubility, consistent with its high degradability in the tested conditions. Altogether, our findings demonstrate that Pluronic F-127 is a promising scaffold for encapsulation of DPSCs and can be considered for cell delivery purposes in tissue engineering.

Periodontal soft tissue root coverage procedures: a consensus report from the AAP Regeneration Workshop.

BACKGROUND: Management of gingival recession defects, a common periodontal condition, using root coverage procedures is an important aspect of periodontal regenerative therapy. The goal of the periodontal soft tissue root coverage procedures group was to develop a consensus report based on the accompanying systematic review of root coverage procedures, including priorities for future research and identification of the best evidence available to manage different clinical scenarios. METHODS: The group reviewed and discussed the accompanying systematic review, which covered treatment of single-tooth recession defects, multiple-tooth recession defects, and additional focused questions on relevant clinical topics. The consensus group members submitted additional material for consideration by the group in advance and at the time of the meeting. The group also identified priorities for future research. RESULTS: All reviewed root coverage procedures provide significant reduction in recession depth, especially for Miller Class I and II recession defects. Subepithelial connective tissue graft (SCTG) procedures provide the best root coverage outcomes. Acellular dermal matrix graft (ADMG) or enamel matrix derivative (EMD) in conjunction with a coronally advanced flap (CAF) can serve as alternatives to autogenous donor tissue. Additional research is needed to do the following: 1) assess the treatment outcomes for multiple-tooth recession defects, oral sites other than maxillary canine and premolar teeth, and Miller Class III and IV defects; 2) assess the role of patient- and site-specific factors on procedure outcomes; and 3) obtain evidence on patient-reported outcomes. CONCLUSIONS: Predictable root coverage is possible for single-tooth and multiple-tooth recession defects, with SCTG procedures providing the best root coverage outcomes. Alternatives to SCTG are supported by evidence of varying strength. Additional research is needed on treatment outcomes for specific oral sites. Clinical Recommendation: For Miller Class I and II single-tooth recession defects, SCTG procedures provide the best outcomes, whereas ADMG or EMD in conjunction with CAF may be used as an alternative.

Application of stem cells derived from the periodontal ligament or gingival tissue sources for tendon tissue regeneration.

Tendon injuries are often associated with significant dysfunction and disability due to tendinous tissue's very limited self-repair capacity and propensity for scar formation. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material present an alternative therapeutic option for tendon repair/regeneration that may be advantageous compared to other current treatment modalities. The MSC delivery vehicle is the principal determinant for successful implementation of MSC-mediated regenerative therapies. In the current study, a co-delivery system based on TGF-ß3-loaded RGD-coupled alginate microspheres was developed for encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs). The capacity of encapsulated dental MSCs to differentiate into tendon tissue was investigated in vitro and in vivo. Encapsulated dental-derived MSCs were transplanted subcutaneously into immunocompromised mice. Our results revealed that after 4 weeks of differentiation in vitro, PDLSCs and GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited high levels of mRNA expression for gene markers related to tendon regeneration (Scx, DCn, Tnmd, and Bgy) via qPCR measurement. In a corresponding in vivo animal model, ectopic neo-tendon regeneration was observed in subcutaneous transplanted MSC-alginate constructs, as confirmed by histological and immunohistochemical staining for protein markers specific for tendons. Interestingly, in our quantitative PCR and in vivo histomorphometric analyses, PDLSCs showed significantly greater capacity for tendon regeneration than GMSCs or hBMMSCs (P < 0.05). Altogether, these findings indicate that periodontal ligament and gingival tissues can be considered as suitable stem cell sources for tendon engineering. PDLSCs and GMSCs encapsulated in TGF-ß3-loaded RGD-modified alginate microspheres are promising candidates for tendon regeneration.

Bone regeneration potential of stem cells derived from periodontal ligament or gingival tissue sources encapsulated in RGD-modified alginate scaffold.

Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD- (arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications.