Periodontal Regenerative Therapy Research Articles

Effect of Amnioguard and Biomesh GTR Membranes with Novabone Putty in the Treatment of Periodontal Osseous Defects—A Communication

(1) Background: Guided tissue regeneration was an effective surgical procedure in the management of intrabony defects and has undergone a number of changes in terms of materials and techniques. The aim of this study is to compare AmnioGuard and BioMesh in combination with NovaBone putty in intrabony defects. (2) Methodology: Ten patients who needed regenerative periodontal therapy were randomly allocated into two groups based on the inclusion criteria. These patients were subjected to phase I therapy followed by which Group A patients were treated with AmnioGuard + NovaBone putty whereas Group B with BioMesh + NovaBone putty. The clinical indices were obtained at baseline, 3 months and 6 months post-operatively while radiographic parameters were obtained at 6 months post-op. (3) Results & Conclusion: At six months after surgery, Group B (33% bone gain) showed a statistically significant change from Group A (16% bone gain) in both the clinical and radiographic measures (p < 0.05).

Comparison of early wound healing using modified papilla preservation technique between enamel matrix derivative and recombinant human fibroblast growth factor.

Enamel matrix derivative (EMD) has demonstrated beneficial effects on wound healing following surgery. However, the effects of recombinant human fibroblast growth factor 2 (rhFGF-2) in periodontal regeneration therapy have not been extensively studied. This retrospective study was conducted to compare the wound healing outcomes of the modified papilla preservation technique (mPPT) between EMD and rhFGF-2 therapies. A total of 79 sites were evaluated for early wound healing using the modified early wound healing index (mEHI), which included 6 items: incision, fibrin clotting, step, redness, swelling, and dehiscence. A numeric analog scale, along with postoperative images of the 6 mEHI items, was established and used for the evaluations. The inter-rater reliability of the mEHI was assessed via intraclass correlation coefficients (ICCs). After adjusting for factors influencing the mPPT, the differences in mEHI scores between the EMD and rhFGF-2 groups were statistically analyzed. Additionally, radiographic bone fill (RBF) was evaluated 6 months after surgery. The ICC of the mEHI was 0.575. The mEHI, redness score, and dehiscence scores were significantly higher in the rhFGF-2 group (n=33) than in the EMD group (n=46). Similar results were observed in the subgroup of patients aged 50 years or older, but not in those younger than 50 years. In the subgroup with non-contained bone defects, related results were noted, but not in the subgroup with contained bone defects. However, early wound healing did not correlate with RBF at 6 months after surgery. Within the limitations of this study, the findings suggest that early wound healing following the use of mPPT with rhFGF-2 is somewhat superior to that observed after mPPT with EMD. However, mEHI should be improved for use as a predictive tool for early wound healing and to reflect clinical outcomes after surgery.

Evaluation of Regenerative Potential of Autologous Platelet Rich Fibrin in Horizontal Bone Defects in Chronic Periodontitis Patients

Background and Aim In periodontal disease alveolar bone loss occurs mainly in two patterns - horizontal and vertical. Most commonly found among these is horizontal pattern of bone loss which received least attention while attempting regenerative periodontal therapy. Hence the objective of this research was to assess the ability of autologous Platelet Rich Fibrin PRF to promote periodontal regeneration in individuals with chronic periodontitis who have horizontal defects.Methods A total of 20 sites with horizontal bone loss were taken in five patients who had met the inclusion criteria. Informed consent was obtained from the patient. All the clinical as well as radiographic parameters were assessed. Open flap debridement with intramarrow penetration and placement of PRF was done for these patients and were followed up for nine months.Results All the patients were consistent with the follow up till nine months. Intergroup comparison of Probing Pocket Depth PPD and Clinical Attachment Level CAL showed significant difference with p lt0.05. Radiographic assessment also showed significant difference compared to baseline with p lt0.05. Conclusion The addition of PRF to horizontal periodontal defects has yielded noteworthy outcomes during a nine-month monitoring period.

Recent advances in GTR scaffolds.

Periodontitis is a serious chronic inflammatory condition that can cause periodontal tissue deterioration and, eventually, tooth loss. Periodontal regenerative therapy using membranes and bone grafting materials, as well as flap debridement and/or flap curettage, have all been used with varying degrees of clinical effectiveness. Current resorbable and non-resorbable membranes serve as a physical barrier, preventing connective and epithelial tissue down growth into the defect and promoting periodontal tissue regeneration. The "perfect" membrane for use in periodontal regenerative therapy has yet to be created, as these conventional membranes have several structural, mechanical, and bio-functional constraints. We hypothesised in this narrative review that the next-generation of guided tissue and guided bone regeneration (GTR/GBR) membranes for periodontal tissue engineering will be a graded-biomaterials that closely mimics the extracellular matrix.

Nano hydroxyapatite in bone regeneration: A literature review

Background: The tissue engineering technique to bone and periodontal tissue regeneration therapy that makes use of one or more of three key factors: signaling molecules, scaffold or supporting matrix, and cells. The graft works as a scaffold and a framework for forming a structure to aid tissue regeneration. One of the most generally used graft substances is hydroxyapatite (HAp). Hydroxyapatite (HAp) is a calcium phosphate derivative that is commonly utilized in bone coatings and cements due to its exceptional biocompatibility. The topic of nano- hydroxyapatite (nHAp) in tissue regeneration therapy will be discussed in this publication. Methods: The method used in writing this article review was a literature review sourced from Google Scholar, Science Direct, and PubMed (MEDLINE). Result: The identification results from a search on Google Scholar, Science Direct, and PubMed (MEDLINE) in which the title contains one or more keywords being searched for, from the article, 55 articles are obtained that have appropriate titles and 14 data are obtained from the results of the review. Discussion: Hydroxyapatite (HAp) is a bioceramic material formed from strong chemical bonds and is included in the bone components of living organisms (in vivo). Conclusion: Hydroxyapatite (HAp) is a bioceramic substance made up of a strong chemical link that is a derivative of calcium phosphate. It is commonly used in coatings or cements on bone because of its excellent biocompatibility.

異種骨移植による歯周組織再生療法を行った18年経過症例

異種骨移植による歯周組織再生療法を行った18年経過症例

Macrophages contribute to periodontal wound healing mainly in the tissue proliferation stage.

The aim of this study was to determine the preliminary role of macrophages in different stages of periodontal healing. Macrophages are promising target cells for periodontal regeneration. However, the stage at which they play a more important role during periodontal repair has not been elucidated till date. First, the dynamic changes in M1 and M2 macrophages were analyzed in a rat periodontal-defect model at Days 1, 3, 5, 7, 14, 21, and 28 post-surgery. Macrophages were then depleted after 1, 6, and 14 days of surgery, and the healing results were evaluated via micro-computed tomography and histopathological detection. Finally, the effects of M1 and M2 macrophages on the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) were verified in vitro. During natural periodontal healing, the number of M1 macrophages increased the most during the early stage of healing (3 days post-operation), and subsequently, it decreased rapidly. The number of M2 macrophages was at its peak during the middle and late stages of tissue healing (5-21 days post-surgery). Interestingly, the highest number of M2 macrophages was observed at 5-14 days post-operation in the alveolar bone, while it was observed at 21 days post-operation in the cementum area. On the first and 14th day post-operation, the clearance of macrophages had no significant effect on tissue healing; however, on the sixth day post-operation, macrophage depletion significantly inhibited tissue regeneration (p < .05). In vitro studies showed that M2 macrophages, rather than M1 macrophages, could significantly promote the proliferation of MSCs (p < .01). It is better to intervene in tissue proliferation phase when a M2 macrophage regulation-based periodontal regenerative therapy is planned in the future.

Regulation of osteogenesis in bone marrow-derived mesenchymal stem cells via histone deacetylase 1 and 2 co-cultured with human gingival fibroblasts and periodontal ligament cells.

This study aimed to determine the regulatory mechanism of bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation mediated by humoral factors derived from human periodontal ligament (HPL) cells and human gingival fibroblasts (HGFs). We analyzed histone deacetylase (HDAC) expression and activity involved in BM-MSC differentiation and determined their regulatory effects in co-cultures of BM-MSCs with HPL cells or HGFs. BM-MSCs can differentiate into various cell types and can, thus, be used in periodontal regenerative therapy. However, the mechanism underlying their differentiation remains unclear. Transplanted BM-MSCs are affected by periodontal cells via direct contact or secretion of humoral factors. Therefore, their activity is regulated by humoral factors derived from HPL cells or HGFs. BM-MSCs were indirectly co-cultured with HPL cells or HGFs under osteogenic or growth conditions and then analyzed for osteogenesis, HDAC1 and HDAC2 expression and activity, and histone H3 acetylation. BM-MSCs were treated with trichostatin A, or their HDAC1 or HDAC2 expression was silenced or overexpressed during osteogenesis. Subsequently, they were evaluated for osteogenesis or the effects of HDAC activity. BM-MSCs co-cultured with HPL cells or HGFs showed suppressed osteogenesis, HDAC1 and HDAC2 expression, and HDAC phosphorylation; however, histone H3 acetylation was enhanced. Trichostatin A treatment remarkably suppressed osteogenesis, decreasing HDAC expression and enhancing histone H3 acetylation. HDAC1 and HDAC2 silencing negatively regulated osteogenesis in BM-MSCs to the same extent as that achieved by indirect co-culture with HPL cells or HGFs. Conversely, their overexpression positively regulated osteogenesis in BM-MSCs. The suppressive effects of HPL cells and HGFs on BM-MSC osteogenesis were regulated by HDAC expression and histone H3 acetylation to a greater extent than that mediated by HDAC activity. Therefore, regulation of HDAC expression has prospects in clinical applications for effective periodontal regeneration, mainly, bone regeneration.

Effects of Temoporfin-Based Photodynamic Therapy on the In Vitro Antibacterial Activity and Biocompatibility of Gelatin-Hyaluronic Acid Cross-Linked Hydrogel Membranes.

This study was performed to design a hydrogel membrane that exhibits antibacterial properties and guides different tissues. Gelatin and hyaluronic acid were used as the main structures, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) was used as a cross-linker, and temoporfin was used as an antibacterial agent. The results revealed that the hydrogel membrane impregnated with temoporfin (HM-T) had a fixation index of &gt;89%. Temoporfin was used in conjunction with a diode laser and did not significantly affect EDC-induced cross-linking. The inhibitory activity of temoporfin showed that HM-T15 and HM-T30 (light exposure for 15 and 30 min, respectively) had remarkable antibacterial properties. The cell survival rate of HM-T15 was 73% of that of the control group, indicating that temoporfin exposure for 15 min did not exert cytotoxic effects on L-929 cells. HM and HM-T15 hydrogel membranes showed good cell adhesion and proliferation after 14 days of dark incubation. However, the hydrogel membrane containing temoporfin significantly reduced pro-inflammatory gene expression. In summary, the HM-T15 group showed potential as a biodegradable material for biocompatible tissue-guarded regeneration membranes with antibacterial properties. This study demonstrated the potential of temoporfin for innovative biomaterials and delivery systems applied to new regenerative periodontal therapies.

Efficacy of biologics for the treatment of periodontal infrabony defects: An American Academy of Periodontology best evidence systematic review and network meta-analysis.

A large variety of biomaterials, biologics and membranes have been utilized in the past 40 years for the regenerative treatment of periodontal infrabony defects. Biologic agents have progressively gained popularity among clinicians and are routinely used for periodontal regeneration. In alignment with the goals of the American Academy of Periodontology (AAP) Best Evidence Consensus (BEC) on the use of biologic mediators in contemporary clinical practice, the aim of this sytematic review was to evaluate the effect of biologic agents, specifically autogenous blood-dervied products (ABPs), enamel matrix derivative (EMD) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB), on the regenerative outcomes of infrabony defects. A detailed systematic search was conducted to identify eligible randomized control trials (RCTs) reporting the outcomes of periodontal regenerative therapy using biologics for the treatment of infrabony defects. A frequentist mixed-modeling approach to network meta-analysis (NMA), characterized by the assessment of three individual components for the treatment of an infrabony defect (the bone graft material [BG], the biologic agent, the application of a barrier membrane) was performed to evaluate and compare the relative efficacy of the different components, on the outcomes of different therapeutic modalities of periodontal regeneration. A total of 153 eligible RCTs were included, with 150 studies contributing to the NMA. The quantitative analysis showed that the addition of biologic agents to bone graft significantly improves the clinical and radiographic outcomes, as compared to BG and flap procedures alone. Barrier membranes enhanced the regenerative outcomes of BG but did not provide further benefits in combination with biologics. The type of BG (autogenous, allogeneic, xenogeneic or alloplastic) and the biologic agent (EMD, platelet-rich fibrin [PRF], platelet-rich plasma [PRP] or rhPDGF-BB) played a significant role on the final outcomes of infrabony defects. Allogeneic and xenogeneic BGs exhibited statistically significantly superior clinical gain than synthetic and autogenous BGs (p<0.05 in all the comparisons), while rhPDGF-BB and PRF demonstrated significantly higher stability of the gingival margin (p<0.01) and radiographic bone fill/gain (p<0.05), together with greater, although not statistically significant, clinical attachment level gain and pocket depth reduction, than EMD and PRP. Overall, rhPDGF-BB exhibited the largest effect size for most parameters, including clinical attachment level gain, pocket depth reduction, less gingival recession and radiographic linear bone gain. Considering the relatively high number of trials presenting an unclear or high risk of bias, the strength of recommendation supporting the use of PRP was judged weak, while the recommendation for EMD, PRF and rhPDGF-BB was deemed in favor. Biologics enhance the outcomes of periodontal regenerative therapy. Combination therapies involving BGs + biologics or BGs + barrier membrane demonstrated to be superior to monotherapies. The choice of the type of BG and biologic agent seems to have significant impact on the clinical and radiographic outcomes of infrabony defects.

Osseous topography in biologically driven flap design in minimally invasive regenerative therapy: A classification proposal.

Minimally invasive periodontal regenerative surgical procedures are a paradigm shift that demands a unique approach encompassing specialized armamentarium, magnification tools, knowledge of handling properties of biomaterials, and specific flap designs. Biologically driven flap design is dictated by optimal soft and hard tissue handling, flap perfusion, and wound stability, all in the pursuit of primary intention healing. The unique architecture of the infrabony defect is a determining factor on incision tracing, boundaries of flap extension, and biomaterial selection. The purpose of this article is to propose a flap design classification based on the osseous topography of infrabony defects during biologically driven minimally invasive surgical periodontal regenerative therapy.

Fluid shear stress promotes periodontal ligament cells proliferation via p38-AMOT-YAP.

Periodontal ligament (PDL) cells are a promising tool for periodontal regeneration therapy. Achieving a sufficient number of PDL cells is essential to PDL regeneration. In our study, appropriate flow shear stress (FSS, 1-6 dyn/cm2) promotes the proliferation of PDL cells. FSS remodels cytoskeleton and focal adhesion in a duration-dependent manner. FSS induces PDL cells to form the actin cap within 10min, flattens the nuclei, and increases the nuclear pore size, which promotes nuclear translocation of Yes-associated protein (YAP). FSS activates p38, which plays a dual function in YAP regulation. p38 regulates the phosphorylation of Akt and cofilin, as well as induced F-actin polymerization to induce YAP activity. In addition, p38 inhibits pLATS and consecutively regulates angiomotin (AMOT) and YAP phosphorylation. AMOT competitively binds to F-actin and YAP to participate in FSS-mediated YAP nuclear translocation and cell proliferation. Taken collectively, our results provide mechanistic insights into the role of p38-AMOT-YAP in FSS-mediated PDL cells proliferation and indicate potential applications in dental regenerative medicine.

Stem cell homing in periodontal tissue regeneration.

The destruction of periodontal tissue is a crucial problem faced by oral diseases, such as periodontitis and tooth avulsion. However, regenerating periodontal tissue is a huge clinical challenge because of the structural complexity and the poor self-healing capability of periodontal tissue. Tissue engineering has led to advances in periodontal regeneration, however, the source of exogenous seed cells is still a major obstacle. With the improvement of in situ tissue engineering and the exploration of stem cell niches, the homing of endogenous stem cells may bring promising treatment strategies in the future. In recent years, the applications of endogenous cell homing have been widely reported in clinical tissue repair, periodontal regeneration, and cell therapy prospects. Stimulating strategies have also been widely studied, such as the combination of cytokines and chemokines, and the implantation of tissue-engineered scaffolds. In the future, more research needs to be done to improve the efficiency of endogenous cell homing and expand the range of clinical applications.

Simultaneous Alveolar Ridge Augmentation and Periodontal Regenerative Therapy Leveraging Recombinant Human Platelet-Derived Growth Factor-BB (rhPDGF-BB): A Case Report

Severe alveolar ridge deficiencies in concomitance with periodontal attachment loss can represent a serious clinical challenge in the context of implant therapy. The present case report describes the management of a complex defect in the esthetic zone via ridge augmentation and periodontal regenerative therapy using a biologic material. A systemically healthy 55-year-old man diagnosed with peri-implantitis around an implant in the maxillary left central incisor position and with severe bone loss on the mesial aspect of the maxillary left lateral incisor underwent several surgical interventions to achieve simultaneous vertical ridge augmentation and periodontal regeneration. These interventions included implant removal, bone augmentation using a composite bone graft (autogenous bone + xenograft particles), and a bioactive protein (recombinant human platelet-derived growth factor), soft tissue augmentation using connective tissue grafts, and peri-implant keratinized mucosa width augmentation via a labial gingival graft strip and a xenogeneic collagen matrix. Substantial gains in vertical bone and clinical attachment were achieved, which allowed for delayed implant placement and subsequent completion of tooth replacement therapy with an implant-supported prosthesis. The present case report demonstrates how simultaneous vertical ridge augmentation and periodontal regeneration can be achieved to manage a challenging clinical situation. Key factors to consider in this type of scenario are proximal bone level, tooth mobility, surgical flap design and management, biomaterial selection, and proper treatment sequencing.

HISTOLOGICAL OUTCOMES AFTER REGENERATIVE PERIODONTAL THERAPY WITH EMDOGAIN

Objective: The aim of this study is to evaluate the histological and clinical outcomes of intrabony defects treatment using regenerative periodontal therapy with enamel matrix proteins (Emdogain, EMD). Material And Method:Ten patients with chronic periodontitis were included in this randomized, controlled clinical study. Two groups received conservative periodontal therapy. In the test group, different teeth received regenerative treatment with EMD. In the control group only conservative periodontal therapy was performed. The following parameters were recorded at baseline and after 8 months: pocket probing depth (PD) and histological examinations. Results:Both groups showed a significant reduction of PD. The teeth treated with EMD showed a significant attachment gain. Within the test group, the radiographic examination of the teeth treated with EMD showed no significant change, whereas the teeth in the control group showed significant bone reduction. Conclusion:Treatment of intrabony defects with EMD may lead to substantially higher gains in clinical attachment and defect filling. The use of EMD in dental practice can prevent further bone loss.

Prognostic factors affecting periodontal regenerative therapy using recombinant human fibroblast growth factor-2: A 3-year cohort study.

IntroductionFibroblast growth factor-2 (FGF-2) has been reported to promote periodontal tissue regeneration. However, no study has investigated the long-term prognosis of periodontal regenerative therapy using FGF-2 to date. The aim of this study was to observe the long-term outcomes as well as to investigate the factors affecting the prognosis of periodontal regenerative therapy using FGF-2.MethodsSixty intrabony defects were prospectively investigated for three years after periodontal regenerative therapy with recombinant human FGF-2 (rhFGF-2) by evaluating probing pocket depth (PPD) and radiographic bone defect depth (RBD). The factors influencing RBD were assessed by conducting a multivariate linear regression analysis after adjusting for confounders.ResultsThe mean age of the participants was 62.4 ± 13.4 years, and baseline PPD and RBD were 6.1 ± 1.9 mm and 4.5 ± 1.8 mm, respectively. At six months, one year, and three years after surgery, PPD and RBD had significantly improved to 4.2 ± 1.7, 3.7 ± 1.4, 4.0 ± 1.9 mm and to 3.08 ± 2.05, 2.73 ± 1.90, 2.51 ± 2.15 mm, respectively. At the three-year examination, a significant positive association was deteced between RBD reduction and RBD at baseline, while the association was not significant between RBD reduction and the radiographic bony angle, number of bony walls of the defect, or the furcation involvement at baseline.ConclusionsrhFGF-2 was effective for alveolar bone regeneration in patients with periodontitis and maintained the improved parameters over the three-year observation period. The radiographic bone defect depth at baseline was found to be the factor affecting the periodontal regenerative therapy using rhFGF-2 in the intrabony defects.Trial registration numberUMIN000027979.

Regeneration of critical-sized grade II furcation using a novel injectable melatonin-loaded scaffold.

Periodontal regenerative therapy using bone-substituting materials has gained favorable clinical significance in enhancing osseous regeneration. These materials should be biocompatible, osteogenic, malleable, and biodegradable. This study assessed the periodontal regenerative capacity of a novel biodegradable bioactive hydrogel template of organic-inorganic composite loaded with melatonin. A melatonin-loaded alginate-chitosan/beta-tricalcium phosphate composite hydrogel was successfully prepared and characterized. Thirty-six critical-sized bilateral class II furcation defects were created in six Mongrel dogs, and were randomly divided and allocated to three cohorts; sham, unloaded composite, and melatonin-loaded. Periodontal regenerative capacity was evaluated via histologic and histomorphometric analysis. Melatonin-treated group showed accelerated bone formation and advanced maturity, with a significant twofold increase in newly formed inter-radicular bone compared with the unloaded composite. The short-term regenerative efficacy was evident 4 weeks postoperatively as a significant increase in cementum length concurrent with reduction of entrapped epithelium. After 8 weeks, the scaffold produced a quality of newly synthesized bone similar to normal compact bone, with potent periodontal ligament attachment. Melatonin-loaded hydrogel template accelerated formation and enhanced quality of newly formed bone, allowing complete periodontal regeneration. Furthermore, the scaffold prevented overgrowth and entrapment of epithelial cells in furcation defects.

Clinical Outcomes of Periodontal Regenerative Therapy Using rhFGF-2 with a Modified Minimally Invasive Surgical Technique for Intrabony Defects: Case Series with a 12-Month Follow-up.

The Modified Minimally Invasive Surgical Technique (M-MIST) was designed to improve wound stability and reduce patient morbidity. This case series aimed to evaluate clinical outcomes of periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 with M-MIST for the treatment of intrabony defects. Following initial periodontal therapy, nine intrabony defects in seven patients received rhFGF-2 therapy. Using M-MIST, a buccal incision was made to gain access to the defect without interdental and lingual incisions. After debridement, rhFGF-2 was applied to the defect. Periodontal parameters were evaluated at baseline and at 3, 6, and 12 months postoperatively. Composite Outcome Measure (COM) and patient-reported outcome measure (PROM, recorded using an oral health-related quality of life [QoL] instrument) were also used for evaluation. At 12 months postoperative, mean probing depth reduction was 4.2 ± 0.8 mm and clinical attachment gain was 4.7 ± 0.7 mm. The mean value for gingival recession was -0.3 ± 0.5 mm. According to COM, the outcomes of the treated sites were successful. An improvement in oral health-related QoL was noted at 12 months compared to after the initial periodontal therapy. This case series shows that rhFGF-2 therapy with M-MIST yields favorable clinical outcomes in the treatment of intrabony defects.

THE ROLE OF STATINS IN PERIODONTAL THERAPY – A REVIEW

Periodontitis is an inflammatory mechanism causing step by step destruction of the periodontal tissues and alveolar bone. Periodontal treatment is intended to restore the tissues damaged by the disease. Various periodontal procedures have been introduced to lower the destruction; statins are being one among them. They are cholesterol-reducing drugs which have shown to promote bone formation and proven to be effective in periodontal therapy. However, statins have numerous actions, with anti-inflammatory and immunomodulatory effects, as well as the capacity to accelerate new bone formation. The pleiotropic effects of statins have been assessed for their prospective advantage in the therapy of several inflammatory and immune-mediated diseases including periodontitis. Such features could be beneficial for periodontal therapies. This article goes through the history and effects of statins and explores its potential role in periodontal regenerative therapy.

An exploratory clinical trial to evaluate the safety and efficacy of combination therapy of REGROTH® and Cytrans® granules for severe periodontitis with intrabony defects.

IntroductionCurrently, flap operation (FOP) using REGROTH® (0.3% basic fibroblast growth factor [FGF-2]) is the standard treatment for periodontal regenerative therapy in Japan. However, the periodontal tissue regenerative effect with REGROTH® monotherapy is inadequate for severe alveolar bone defects. Therefore, in this study, we evaluated the safety and effectiveness of periodontal regenerative therapy for patients with severe periodontitis using REGROTH® (test medicine) combined with Cytrans® Granules (test device: carbonated apatite granules), which is a new artificial bone.MethodsThe study participants included 10 patients with severe periodontitis (mean age: 47.4 years). All participants provided written informed consents. In each patient, the intrabony defect site (mean bone defect depth: 5.7 mm) was defined as the test site. FOP was performed for the test site after the baseline investigation; moreover, the test medicine and test device were administered simultaneously. Furthermore, the observation of subjects’ general condition and test sites was conducted and the blood, urine, and periodontal tissue tests were performed up to 36 weeks after FOP. The rate of bone increase (%), clinical attachment level (CAL), probing pocket depth (PPD), bleeding on probing (BOP), tooth mobility (Mo), width of keratinized gingiva (KG), gingival recession (REC), gingival index (GI), and plaque index (PlI) were evaluated during the periodontal tissue investigation.ResultsAs the primary endpoint, no adverse events related to the test medicine and test device occurred during the entire observation period of this study. Regarding the secondary endpoints, there was a significant increase in new alveolar bone (p = 0.003) and CAL acquisition (p = 0.001) as well as decrease in PPD (p = 0.002) and BOP (p = 0.016) at 36 weeks after administration of the test medicine and test device compared with the preoperative values. Furthermore, at 36 weeks after surgery, the Mo, GI, and PlI decreased to preoperative levels at 40%, 60%, and 30% of sites, respectively. However, at 36 weeks after surgery, there was no difference in KG and REC compared with their preoperative values.ConclusionsThe safety of periodontal regenerative therapy using the test medicine in combination with the abovementioned test device was confirmed. In addition, it was suggested that this periodontal regenerative therapy is effective for tissue regeneration in severe alveolar bone defects.This clinical trial was conducted after registering and publicizing as a specified clinical trial in the Japan registry of clinical trials (jRCTs051190045).