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Objective: The predictability and long-term success of periodontal regeneration begins with oral hygiene education, disease management, and an individually tailored periodontal maintenance protocol. The treatment outcomes could be enhanced when biologics and bone grafts are combined. The aim of this report was to describe the outcome of two complex infrabony defects in the same patient treated with recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and freeze-dried bone allograft (FDBA) over 10 years. Case presentation: Two complex infrabony defects were treated following guided tissue regeneration principles and procedures. Fullthickness flaps were raised to allow visualization of the defects. The areas were debrided, and exposed root surfaces were planed. FDBA and rhPDGF-BB were combined to fill both defects. A collagen membrane was used over the bone graft in one case. The flaps were reapproximated to achieve primary closure. The patient was seen for regular periodontal maintenance visits and clinical and radiographic follow-ups over 10 years. Throughout the examination periods, the probing depths improved without bleeding on probing, and there was radiographic evidence of bone regeneration. Conclusion: The growth factorinfused bone graft was successfully utilized for periodontal regeneration in complex bony defects. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Key points Plain language summary Recombinant human fibroblast growth factor‐2 (rhFGF‐2) has been shown to effectively promote the formation of new periodontal tissues, and its efficacy has been demonstrated in clinical settings. Moreover, the clinical and radiographic outcomes in the treatment of periodontal infrabony defects can be improved by using rhFGF‐2 in combination with a bone substitute. Here, we present a case of four‐wall bone defect in a tooth treated by combination regenerative therapy using rhFGF‐2 and beta‐tricalcium phosphate (β‐TCP).A 43‐year‐old male with a four‐wall bone defect in tooth #28 was subjected to combination therapy with rhFGF‐2 and β‐TCP. Periodontal clinical parameters and radiographic images were evaluated at the first visit, after the initial periodontal treatment, and after 4 months and 4 years postoperation.Although gingival recession and nonvital pulp were observed postoperation, improvements in the periodontal parameters and radiographic outcomes were subsequently recorded.Periodontal regenerative therapy with a combination of rhFGF‐2 and β‐TCP showed great potential in the treatment of four‐wall bone defects of teeth. Periodontal regenerative therapy using recombinant human fibroblast growth factor‐2 (rhFGF‐2) and beta‐tricalcium phosphate (β‐TCP) showed immense potential in the treatment of four‐wall bone defect in teeth. In addition to using computed tomography for assessing bone defects and root morphologies, an evaluation of root canal morphology and pulp diagnosis is essential for understanding the internal and external aspects of the defect, which would aid in tooth preservation. Appropriate periodontal and endodontic treatments enabled tooth preservation following apical periodontitis after periodontal regenerative therapy. This case report focuses on a new approach for the treatment of a four‐wall bone defect, a significant dental issue in which the bone around the tooth is damaged, thereby decreasing the stability of the tooth. We treated a 43‐year‐old male patient with a combination of two key components: the growth factor rhFGF‐2, which helps promote the growth of new tissues, and the synthetic bone graft substitute β‐TCP, which acts as a substitute for the missing bone. Over the course of 4 years, we monitored the patient's progress using dental exams and X‐ray photos. Despite some minor side effects, such as gum recession and the loss of tooth vitality, the overall condition of the tooth and surrounding bone showed significant improvement. This combination therapy shows promise in repairing similar bone defects, which would help save teeth that might otherwise be lost. [ABSTRACT FROM AUTHOR]

The periodontal ligament (PDL) is a fibrous connective tissue that connects the cementum of the root to the alveolar bone. PDL stem cells (PDLSCs) contained in the PDL can differentiate into cementoblasts, osteoblasts, and PDL fibroblasts, with essential roles in periodontal tissue regeneration. Therefore, PDLSCs are expected to be useful in periodontal tissue regeneration therapy. In a previous study, we differentiated induced pluripotent stem cells (iPSCs) into PDLSC-like cells (iPDLSCs), which expressed PDL-related markers and mesenchymal stem cell (MSC) markers; they also exhibited high proliferation and multipotency. However, the iPSCs used in this differentiation method were cultured on mouse embryonic fibroblasts; thus, they constituted on-feeder iPSCs (OF-iPSCs). Considering the risk of contamination with feeder cell-derived components, iPDLSCs differentiated from OF-iPSCs (ie, OF-iPDLSCs) are unsuitable for clinical applications. In this study, we aimed to obtain PDLSC-like cells from feeder-free iPSCs (FF-iPSCs) using OF-iPDLSC differentiation method. First, we differentiated FF-iPSCs into neural crest cell-like cells (FF-iNCCs) and confirmed that FF-iNCCs expressed NCC markers (eg, Nestin and p75NTR). Then, we cultured FF-iNCCs on human primary PDL cell-derived extracellular matrix for 2 weeks; the resulting cells were named FF-iPDLSCs. FF-iPDLSCs exhibited higher expression of PDL-related and MSC markers compared with OF-iPDLSCs. FF-iPDLSCs also demonstrated proliferation and multipotency in vitro. Finally, we analyzed the ability of FF-iPDLSCs to form periodontal tissue in vivo upon subcutaneous transplantation with β-tricalcium phosphate scaffolds into dorsal tissues of immunodeficient mice. Eight weeks after transplantation, FF-iPDLSCs had formed osteocalcin-positive bone/cementum-like tissues and collagen 1-positive PDL-like fibers. These results suggested that we successfully obtained PDLSC-like cells from FF-iPSCs. Our findings will contribute to the development of novel periodontal regeneration therapies. [ABSTRACT FROM AUTHOR]

Guided tissue regeneration (GTR) has been widely used in the periodontal treatment of intrabony and furcation defects for nearly four decades. The treatment outcomes have shown effectiveness in reducing pocket depth, improving attachment gain and bone filling in periodontal tissue. Although applying GTR could reconstruct the periodontal tissue, the surgical indications are relatively narrow, and some complications and race ethic problems bring new challenges. Therefore, it is challenging to achieve a consensus concerning the clinical benefits of GTR. With the appearance of stem cell-based regenerative medicine, mesenchymal stem/stromal cells (MSCs) have been considered a promising cell resource for periodontal regeneration. In this review, we highlight preclinical and clinical periodontal regeneration using MSCs derived from distinct origins, including non-odontogenic and odontogenic tissues and induced pluripotent stem cells, and discuss the transplantation procedures, therapeutic mechanisms, and concerns to evaluate the effectiveness of MSCs. [ABSTRACT FROM AUTHOR]

Objectives: Thermosensitive hydrogels are now among the most commonly used biomaterials in tissue engineering. Due to their unique characteristics, this review aimed to evaluate the suitability of thermosensitive hydrogels in periodontal regeneration. Material and Methods: PubMed, Scopus, and Web of Science databases were searched until March 25, 2024, to retrieve relevant articles. The eligibility criteria for the included studies were determined by the designed PICO elements. Results from each included study were extracted, focusing on the three main areas: thermosensitivity, cellular characteristics, and in vivo characteristics. Results: Nineteen studies were included in our study. The thermosensitivity assessment of the hydrogels indicated a range of sol–gel transition times from 40 s to 20 min based on the type of polymers and the fabrication process. The cellular characterization was assessed based on three main cellular behaviors: cellular viability/proliferation, differentiation, and migration. The in vivo characterization was performed based on two main approaches: radiographic and histologic evaluation. Conclusions: The results indicated that the addition of bioactive agents could enhance the in vivo efficacy of thermosensitive hydrogels in periodontal regeneration through three main areas: antimicrobial, anti‐inflammatory, and regenerative effects. [ABSTRACT FROM AUTHOR]

This narrative review delves into the molecular mechanisms of hyaluronic acid (HA) and re-epithelializing agents in the context of periodontal regeneration. Periodontitis, characterized by chronic inflammation and the destruction of tooth-supporting tissues, presents a significant challenge in restorative dentistry. Traditional non-surgical therapies (NSPTs) sometimes fail to fully manage subgingival biofilms and could benefit from adjunctive treatments. HA, with its antibacterial, antifungal, anti-inflammatory, angiogenic, and osteoinductive properties, offers promising therapeutic potential. This review synthesizes the current literature on the bioactive effects of HA and re-epithelializing agents, such as growth factors and biomaterials, in promoting cell migration, proliferation, and extracellular matrix (ECM) synthesis. By modulating signaling pathways like the Wnt/β-catenin, TGF-β, and CD44 interaction pathways, HA enhances wound healing processes and tissue regeneration. Additionally, the role of HA in facilitating cellular crosstalk between epithelial and connective tissues is highlighted, as it impacts the inflammatory response and ECM remodeling. This review also explores the combined use of HA with growth factors and cytokines in wound healing, revealing how these agents interact synergistically to optimize periodontal regeneration. Future perspectives emphasize the need for further clinical trials to evaluate the long-term outcomes of these therapies and their potential integration into periodontal treatment paradigms. [ABSTRACT FROM AUTHOR]

Objectives: This randomized controlled trial compared the outcomes of recombinant human fibroblast growth factor (rhFGF)-2 plus carbonate apatite (CO3Ap) granules with rhFGF-2 alone in the treatment of intrabony periodontal defects. Materials and methods: Patients with Stage III Grade B/C periodontitis who had completed initial periodontal therapy and had intrabony defects with a depth of ≥ 3 mm were included. Defects were treated solely with rhFGF-2 (control) or rhFGF-2 plus CO3Ap (test). Periodontal parameters and a patient-reported outcome measure (PROM) were assessed at baseline, at 6, 9 and 12 months postoperatively. The primary outcome was the change in clinical attachment level (CAL) from baseline to 12 months postoperatively. Using the Friedman test with Dunn's post-test, intragroup data were compared over time, and Mann-Whitney U test was used to assess intergroup data at each time point. Results: Forty-eight sites in 38 patients were subjected to analysis. At 12 months postoperatively, CAL in both groups showed a significant improvement from baseline (p < 0.001). CAL gain was 3.4 ± 1.3 mm in the test group and 3.2 ± 1.2 mm in the control group, with no significant intergroup difference (p = 0.567). Radiographic bone fill in the test group (67.2%) was significantly greater than in the control group (32.4%) (p < 0.001). PROM scores showed no difference between groups. Conclusions: At 12 months, the outcomes including CAL gain and PROM showed no significant differences between groups, although the combination treatment enhanced radiographic bone fill. Clinical relevance: The use of rhFGF-2 (with/without CO3Ap) could lead to significant improvement in clinical parameters in the treatment of intrabony periodontal defects. The benefit of adding CO3Ap to rhFGF-2 therapy needs further evaluation. Clinical Trial Registration Number: The University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) : UMIN000040783. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of platelet-rich fibrin (PRF) in the treatment of grade II furcation mandibular molars. Materials and Methods: We enrolled 12 patients with 24 mandibular class II furcation defects in this randomized clinical trial with a split-mouth design. These defects were treated with either open flap debridement (OFD) in conjunction with PRF (test group) or only OFD (control group). We recorded and assessed clinical parameters (probing pocket depth [PPD], gingival recession [GR], and vertical and horizontal clinical attachment level [VCAL and HCAL, respectively]), radiographic parameters (bone defect fill [%BF]), and microbiological parameters at baseline and 6 months after treatment. Results: After treatment, PPD, VCAL, HCAL, BF, and microbiological parameters were significantly reduced in both groups. All clinical and radiographic parameters showed significant improvement at the sites that had been treated with PRF and OFD compared with those that had been treated with OFD alone. Among 24 furcation defects in both groups, 10 showed a significantly improved clinical condition and 14 remained at the initial grade. There were no more severe conditions recorded after treatment. Conclusion: Within the limitation of this article, we have demonstrated the effectiveness of PRF in the regenerative treatment of grade II furcation defects. [ABSTRACT FROM AUTHOR]

Background: Periodontal intra-bony defects are challenging conditions in dental practice, often requiring regenerative approaches for successful treatment. This clinical study aimed to compare the effectiveness of plasma rich in growth factors (PRGF) versus xenogenic bone graft (BXG) in addressing intra-bony defects. Methods: Forty patients aged between 30 and 50 years presenting with generalized periodontitis were included. The study assessed various parameters, including relative attachment level (RAL); probing pocket depth (PPD); gingival marginal level (GML); intra-bony defect depth (IBDD) at baseline, 3, and 6 months; and level of pain, post-operative bleeding, and swelling, as patient-reported outcomes during the first seven days post operation. Results: The results revealed that both PRGF and BXG treatments led to significant reductions in IBDD over the 6-month study period. PRGF demonstrated significant advantages in GML enhancement and post-operative pain management during the initial post-treatment days. However, BXG showed a significantly greater reduction in IBDD compared to PRGF. Post-operative bleeding and swelling levels were comparable between the two treatments. Conclusions: These findings underscore the efficacy of both PRGF and BXG in periodontal regeneration, with treatment decisions guided by patient-specific factors and clinical goals. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs), characterized by their undifferentiated and multipotent nature, can be derived from various sources, including bone marrow, adipose, and dental tissues. Among these, dental MSCs (DSCs) exhibit universal MSC characteristics and are attracting considerable attention for regenerating oral and craniofacial tissues. This review provides a contemporary overview of recently published clinical studies using DSCs for various orodental and maxillofacial regenerative applications, including bone, periodontal, and endodontic regeneration. It also explores the utilization of DSCs in treating systemic conditions, exemplified by their application in managing conditions such as COVID-19 and osteoarthritis. The available evidence underscores the potential of DSCs and their secretome as efficacious tools in regenerative medicine for both dental and nondental clinical applications, supporting the continued promise of stem cell–based therapies. It is nevertheless evident that there are a number of important challenges that restrict the widespread utilization of DSCs, namely, difficulty in standardizing autologous preparations, insufficient cell surface marker characterization, high production costs, and regulatory compliance requirements. Further, the unique requirements of dental applications, especially complex structures such as the periodontium, where temporospatial control over the healing process is required, necessitate the combination of stem cells with appropriate scaffolds according to the principles of tissue engineering. There is currently insufficient evidence to support the clinical translation of DSCs into clinical practice, and phase 3 clinical trials with standardized protocols for cell sourcing, propagation, dosing, and delivery are required to move the field forward. In summary, this review provides a contemporary overview of the evolving landscape of stem cell therapy, offering insights into the latest developments and trends as well as the challenges that need to be addressed for the widespread application of DSC-based cell therapies. [ABSTRACT FROM AUTHOR]

Background and Objectives: Periodontal therapy aims to arrest the progression of periodontal diseases and possibly to regenerate the periodontal apparatus. To shift healing from repair to regeneration, the blood clot that fills the periodontal defect and remains in contact with structures such as tooth root, mucosa and bone needs to be stable, which is a reason why the treatment of non-containing periodontal bone defects, in which the clot may undergo displacement, is challenging. The gingival soft tissue, properly sutured, may act as a wall for blood clot stabilization. Knowledge on the response of the blood clot to stress and how it might vary according to the characteristics of the tissues it gets in contact with might be deepened. The aim of this study was to investigate in vitro, by means of a micro-loading device, the response of the complex formed by a blood clot and diverse tissues, simulating those involved in periodontal regeneration, to a displacing tensile test. Materials and Methods: Experimental samples made of two layers of either hard dental tissues, cancellous bone or oral mucosa, between which fresh blood was interposed, underwent a debonding experiment by means of a micro-loading device that measured their response to uniaxial tensile stress. Results: The peak of tensile stress and the overall work needed for the complete rupture of the clot's fibrin filaments were significantly higher for hard dental tissues than for other tissues. However, mucosa sustained the highest maximal strain in terms of relative displacement between the plates of the micro-loading device to accomplish the complete rupture of the fibrin filaments compared to the other tissues, suggesting that the mucosa might act as a stable interface with the clot and be able to sustain tensile stresses. Conclusions: This in vitro study seems to support the use of mucosa to act as a wall for regenerative procedures of suprabony periodontal defects given its capability to form a stable interface with the clot. [ABSTRACT FROM AUTHOR]

Guided tissue regeneration (GTR) has been widely used in the periodontal treatment of intrabony and furcation defects for nearly four decades. The treatment outcomes have shown effectiveness in reducing pocket depth, improving attachment gain and bone filling in periodontal tissue. Although applying GTR could reconstruct the periodontal tissue, the surgical indications are relatively narrow, and some complications and race ethic problems bring new challenges. Therefore, it is challenging to achieve a consensus concerning the clinical benefits of GTR. With the appearance of stem cell-based regenerative medicine, mesenchymal stem/stromal cells (MSCs) have been considered a promising cell resource for periodontal regeneration. In this review, we highlight preclinical and clinical periodontal regeneration using MSCs derived from distinct origins, including non-odontogenic and odontogenic tissues and induced pluripotent stem cells, and discuss the transplantation procedures, therapeutic mechanisms, and concerns to evaluate the effectiveness of MSCs.

Periodontal regeneration is a multifaceted therapeutic approach to restore the tooth-supporting structures lost due to periodontal diseases. This manuscript explores the intricate interactions between regenerative therapies and the oral microbiome, emphasizing the critical role of microbial balance in achieving long-term success. While guided tissue regeneration (GTR), bone grafting, and soft tissue grafting offer promising outcomes in terms of tissue regeneration, these procedures can inadvertently alter the oral microbial ecosystem, potentially leading to dysbiosis or pathogenic recolonization. Different grafting materials, including autografts, allografts, xenografts, and alloplasts, influence microbial shifts, with variations in the healing timeline and microbial stabilization. Biologics and antimicrobials, such as enamel matrix derivatives (EMD) and sub-antimicrobial dose doxycycline (SDD), play a key role in promoting microbial homeostasis by supporting tissue repair and reducing pathogenic bacteria. Emerging strategies, such as enzyme-based therapies and antifouling materials, aim to disrupt biofilm formation and enhance the effectiveness of periodontal treatments. Understanding these microbial dynamics is essential for optimizing regenerative therapies and improving patient outcomes. The future of periodontal therapy lies in the development of advanced materials and strategies that not only restore lost tissues but also stabilize the oral microbiome, ultimately leading to long-term periodontal health.

Objective: To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing/regeneration in intrabony defects. Method and mater-ials: Intrabony defects were surgically created in the mandible of three minipigs. Twelve defects were randomly treated with either rAmelX and carrier (test group) or with the carrier only (control group). At 3 months following reconstructive surgery, the animals were euthanized, and the tissues histologically processed. Thereafter, descriptive histology, histometry, and statistical analyses were performed. Results: Postoperative clinical healing was uneventful. At the defect level, no adverse reactions (eg, suppuration, abscess formation, unusual inflammatory reaction) were observed with a good biocompatibility of the tested products. The test group yielded higher values for new cementum formation (4.81 ± 1.17 mm) compared to the control group (4.39 ± 1.71 mm) without reaching statistical significance (P= .937). Moreover, regrowth of new bone was greater in the test compared to the control group (3.51 mm and 2.97 mm, respectively, P = .309). Conclusions: The present results provided for the first-time histologic evidence for periodontal regeneration following the use of rAmelX in intrabony defects, thus pointing to the potential of this novel recombinant amelogenin as a possible alternative to regenerative materials from animal origins. [ABSTRACT FROM AUTHOR]

Objectives: Inflammation and osteoclast activity are important in various diseases, including periodontitis and osteoporosis. Farnesoid X receptor (FXR) has been identified as a promising target for modulating these processes. This study delved into the impact of FXR agonists on inflammation and periodontal regeneration using periodontitis models. Material and methods: The RAW264.7 and gingival fibroblast cells were divided into five groups: control, lipopolysaccharide (LPS), LPS combined with FXR agonist, LPS with si-FXR, and LPS with si-FXR alongside FXR agonist. FXR expression and pro-inflammatory cytokine levels were quantified. Osteoclast activity was evaluated by observing morphological alterations and tartrate-resistant acid phosphatase staining. The rats were used to establish periodontitis models and received varying doses of FXR agonist. Bone health metrics were assessed, and the expressions of runt-related transcription factor 2 (RUNX2), integrin-binding sialoprotein (IBSP), nuclear factor-kappa B (NF-kB), phosphorylated nuclear factor-kappa B (p-NF-kB), toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) were determined. Results: FXR suppressed the release of pro-inflammatory cytokines in both LPS-stimulated RAW264.7 and gingival fibroblast cells, while curbing osteoclastogenesis. In periodontitis rat models, FXR agonist administration caused notable enhancement in bone density. Moreover, FXR agonist mitigated periodontal inflammation, decreased periodontal index markers and suppressed the expressions of NF-kB, p-NF-kB, TLR4, and TLR2, but upregulated the expressions of RUNX2 and IBSP. Conclusion: The data underscores the potential of FXR agonists in attenuating inflammation and periodontal regeneration, both in vitro and in vivo. This suggests the potential therapeutic application of FXR agonists in conditions marked by inflammation and bone degradation. [ABSTRACT FROM AUTHOR]

Objectives: To assess the association between the baseline radiographic defect angle and the long-term clinical outcomes following periodontal regenerative therapy with enamel matrix derivative (EMD). Method and materials: Baseline periapical radiographs obtained from a cohort of patients treated with periodontal regenerative therapy were digitized and the radiographic angle width between the root surface and the bony wall of the adjacent intraosseous defect was calculated and reported (in degrees). Changes in pocket probing depth (PD) and clinical attachment level (CAL) were assessed and reported (in mm). Clinical outcomes were evaluated at baseline (T0), 6 months following therapy (T1), and at the latest follow-up (T2). Results: Thirty-eight defects in 26 patients enrolled in supportive periodontal care for a mean period of 10.4 years (range 8.0 to 15.5 years) were available for analysis. The mean PD change between T0 and T2 was 2.33 ± 1.66 mm at teeth with a defect angle width < 20 degrees and 0.86 ± 1.66 mm at teeth with a defect angle width > 30 degrees (P = .021). When the baseline radiographic angle width was < 20 degrees the probability of obtaining a CAL gain > 3 mm was 1.5-times higher (95% CI 0.19 to 13.8) at T1 and 2.5-times higher (95% CI 0.40 to 15.6) at T2 compared with defects with a radiographic angle width > 30 degrees. Conclusion: Within their limitations, these results indicate that pretherapeutic measurement of the radiographic defect angle width might provide relevant information on the short-/long-term clinical outcomes following regenerative periodontal therapy with EMD. [ABSTRACT FROM AUTHOR]

Abstract Background The transplantation of periodontal ligament stem cells (PDLSCs) has been shown to enhance periodontal regeneration in animal models and clinical trials. However, it is not known whether PDLSCs are antibacterial and whether this affects oral microbiota and periodontal regeneration. Methods We isolated human PDLSCs from periodontal ligament of extracted teeth. Rats’ periodontal fenestration defects were prepared, and treated with PDLSC injections (Cell group), using saline injections (Saline group) as the control. The oral microbiota was explored by 16 S rDNA sequencing and compared with that before surgery (PRE group). The antibacterial property of PDLSCs and its underlying mechanism were tested in vitro. Results Microbiome analyses reveal a decreased biodiversity, a changed community structure, and downregulated community functions of the oral microbiome in the Saline group. PDLSCs injections enhance periodontal regeneration, reverse the decrease in diversity, and increase the abundance of non-pathogenic bacterial Bifidobacterium sp. and Lactobacillus sp., making the oral microbiome similar to that of the PRE group. In vitro, PDLSCs inhibit the growth of Staphylococcus aureus, Escherichia coli, and Fusobacterium nucleatum. The main mechanism of action is postulated to involve production of the cationic antimicrobial peptide LL-37. Conclusions Our findings reveal that PDLSC injections enhance periodontal regeneration and regulate the oral microbiome to foster an oral cavity microenvironment conducive to symbiotic microbiota associated with health.

Introduction: Root biomodification in periodontal therapy aims at removing the smear layer and enhances the clot stability necessary for periodontal regeneration. Citric Acid (CA), EDTA, fibronectin has been used routinely. But if used injudiciously acidic erosion of the periodontal tissues might occur. Apple Cider Vinegar (ACV) an organic acetic has been reported to possess antimicrobial, anti-inflammatory and antioxidant effects. Aim: To assess the effect of smear layer removal and fibrin clot adhesion of ACV in comparison to CA on periodontally affected teeth. Materials and Methods: This pilot study was conducted at Sri Venkateswara Dental College and Hospital, Chennai, India, for three months, starting in January 2024 and ending in March 2024. 8 Teeth extracted due to periodontal reasons were cleaned, scaled and root planed. From the extracted teeth 16 dentin block samples were obtained, of which eight underwent CA testing (Control group) and eight underwent ACV testing (test group). The SEM analysis was done to assess the efficiency of smear layer removal and fibrin clot adhesion. Results: Under qualitative Scanning Electron Microscope (SEM) analysis, though ACV (50%) and CA (50%) group exhibited significant level of smear layer removal, complete dentinal tubule opening (RMSI score 2) was observed only in ACV category. In regard to Blood Element Adhesion Index (BEAI) both the groups demonstrated moderate fibrin clot adhesion (BEA score 2) in 50% of their samples. Considering both the parameters, root conditioning effects of ACV was better than CA. Conclusion: Teeth treated with ACV had a comparable effect as the CA in terms of root biomodification. This novel agent with several medicinal effects can be considered for future studies to determine its regenerative effectiveness.

Abstract The recent development of nanobiomaterials has shed some light on the field of periodontal tissue regeneration. Laponite (LAP), an artificially synthesized two-dimensional (2D) disk-shaped nanosilicate, has garnered substantial attention in regenerative biomedical applications owing to its distinctive structure, exceptional biocompatibility and bioactivity. This study endeavors to comprehensively evaluate the influence of LAP on periodontal regeneration. The effects of LAP on periodontal ligament cells (PDLCs) on osteogenesis, cementogenesis and angiogenesis were systematically assessed, and the potential mechanism was explored through RNA sequencing. The results indicated that LAP improved osteogenic and cementogenic differentiation of PDLCs, the regulatory effects of LAP on PDLCs were closely correlated with activation of PI3K-AKT signaling pathway. Moreover, LAP enhanced angiogenesis indirectly via manipulating paracrine of PDLCs. Then, LAP was implanted into rat periodontal defect to confirm its regenerative potential. Both micro-CT and histological analysis indicated that LAP could facilitate periodontal tissue regeneration in vivo. These findings provide insights into the bioactivity and underlying mechanism of LAP on PDLCs, highlighting it might be a potential therapeutic option in periodontal therapy.

Abstract Background Periodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period. Methods To trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation. Results In vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type macrophages, fewer TRAP + osteoclasts, and an upregulated OPG/RANKL ratio were detected in the E-DFSC group compared to the control group, which indicated that immune balance tilts towards healing and bone formation. Conclusion The xenogenous implanted DFSCs can induce the N2 phenotype of neutrophils in the early stage, which can activate the innate immune mechanism of the host to promote periodontal tissue regeneration.

Amnion-chorion membrane (ACM) has emerged as a versatile biomaterial with immense potential in various medical and dental applications, including periodontal therapy. ACM possesses unique properties, including a bioactive matrix rich in growth factors, anti-inflammatory and antibacterial attributes, and a remarkably thin, self-adherent structure. These characteristics make ACM well suited for various periodontal applications, such as intrabony defect treatment, gingival recession management, socket preservation, papillary preservation, and sinus membrane repair. This review offers comprehensive details of the properties, applications, and implications of ACM membranes in the realm of periodontal treatment.

Background: The transplantation of periodontal ligament stem cells (PDLSCs) has been shown to enhance periodontal regeneration in animal models and clinical trials. However, it is not known whether PDLSCs are antibacterial and whether this affects oral microbiota and periodontal regeneration. Methods: We isolated human PDLSCs from periodontal ligament of extracted teeth. Rats' periodontal fenestration defects were prepared, and treated with PDLSC injections (Cell group), using saline injections (Saline group) as the control. The oral microbiota was explored by 16 S rDNA sequencing and compared with that before surgery (PRE group). The antibacterial property of PDLSCs and its underlying mechanism were tested in vitro. Results: Microbiome analyses reveal a decreased biodiversity, a changed community structure, and downregulated community functions of the oral microbiome in the Saline group. PDLSCs injections enhance periodontal regeneration, reverse the decrease in diversity, and increase the abundance of non-pathogenic bacterial Bifidobacterium sp. and Lactobacillus sp., making the oral microbiome similar to that of the PRE group. In vitro, PDLSCs inhibit the growth of Staphylococcus aureus, Escherichia coli, and Fusobacterium nucleatum. The main mechanism of action is postulated to involve production of the cationic antimicrobial peptide LL-37. Conclusions: Our findings reveal that PDLSC injections enhance periodontal regeneration and regulate the oral microbiome to foster an oral cavity microenvironment conducive to symbiotic microbiota associated with health. [ABSTRACT FROM AUTHOR]

The recent development of nanobiomaterials has shed some light on the field of periodontal tissue regeneration. Laponite (LAP), an artificially synthesized two-dimensional (2D) disk-shaped nanosilicate, has garnered substantial attention in regenerative biomedical applications owing to its distinctive structure, exceptional biocompatibility and bioactivity. This study endeavors to comprehensively evaluate the influence of LAP on periodontal regeneration. The effects of LAP on periodontal ligament cells (PDLCs) on osteogenesis, cementogenesis and angiogenesis were systematically assessed, and the potential mechanism was explored through RNA sequencing. The results indicated that LAP improved osteogenic and cementogenic differentiation of PDLCs, the regulatory effects of LAP on PDLCs were closely correlated with activation of PI3K-AKT signaling pathway. Moreover, LAP enhanced angiogenesis indirectly via manipulating paracrine of PDLCs. Then, LAP was implanted into rat periodontal defect to confirm its regenerative potential. Both micro-CT and histological analysis indicated that LAP could facilitate periodontal tissue regeneration in vivo. These findings provide insights into the bioactivity and underlying mechanism of LAP on PDLCs, highlighting it might be a potential therapeutic option in periodontal therapy. [ABSTRACT FROM AUTHOR]

Introduction. Periodontal regeneration is defined histologically as the new formation of tooth-supporting tissues, which includes alveolar bone, periodontal ligament and cementum, on a previously lost root surface. The application of protein derivatives of the enamel-derived matrix (EDM) was introduced as an alternative to obtain periodontal regeneration, in furcation affectations and intraosseous periodontal defects. Furcation involvement is bone resorption in the bifurcation or trifurcation area of a multirooted tooth. Case report. 38-year-old, female patient, ASA I, who presented for consultation for a restoration change in OD 36. On clinical and radiographic examination revealed a grade II furcation defect according to Hamp, with loss of horizontal support > 3 mm, but without passing the probe and vertical probing depth < 3 mm at the vestibular and lingual midpoint, presence of bleeding on probing. Once the hygienic phase was completed, periodontally regeneration with EDM (Emdogain®). Reduction of a grade II furcation defect to grade I was achieved after six months, with radiographic bone filling in the furcation area and vertical and horizontal probing < 3 mm. Conclusions. Class II furcation defects are the most predictable to obtain complete furcation closure or Class II to I. [ABSTRACT FROM AUTHOR]

Introduction: Root biomodification in periodontal therapy aims at removing the smear layer and enhances the clot stability necessary for periodontal regeneration. Citric Acid (CA), EDTA, fibronectin has been used routinely. But if used injudiciously acidic erosion of the periodontal tissues might occur. Apple Cider Vinegar (ACV) an organic acetic has been reported to possess antimicrobial, anti-inflammatory and antioxidant effects. Aim: To assess the effect of smear layer removal and fibrin clot adhesion of ACV in comparison to CA on periodontally affected teeth. Materials and Methods: This pilot study was conducted at Sri Venkateswara Dental College and Hospital, Chennai, India, for three months, starting in January 2024 and ending in March 2024. 8 Teeth extracted due to periodontal reasons were cleaned, scaled and root planed. From the extracted teeth 16 dentin block samples were obtained, of which eight underwent CA testing (Control group) and eight underwent ACV testing (test group). The SEM analysis was done to assess the efficiency of smear layer removal and fibrin clot adhesion. Results: Under qualitative Scanning Electron Microscope (SEM) analysis, though ACV (50%) and CA (50%) group exhibited significant level of smear layer removal, complete dentinal tubule opening (RMSI score 2) was observed only in ACV category. In regard to Blood Element Adhesion Index (BEAI) both the groups demonstrated moderate fibrin clot adhesion (BEA score 2) in 50% of their samples. Considering both the parameters, root conditioning effects of ACV was better than CA. Conclusion: Teeth treated with ACV had a comparable effect as the CA in terms of root biomodification. This novel agent with several medicinal effects can be considered for future studies to determine its regenerative effectiveness. [ABSTRACT FROM AUTHOR]

Aim: To compare the clinical and radiographic outcomes of flapless procedure alone or in combination with enamel matrix derivatives (EMD) in the treatment of deep intrabony defects. Materials and Methods: Forty‐six patients re‐evaluated after non‐surgical therapy were randomly assigned to the test (flapless with EMD) or control group (flapless alone). Clinical measurements were recorded pre‐surgery and at 6 and 12 months after surgery, and radiographic measurements were taken pre‐surgery and after 12 months. Results: Forty‐six patients completed the study. Improvements were observed in both groups at 12 months for mean clinical attachment level (CAL) gain, with significant differences between test (3.9 ± 1.1 mm) and control groups (3.0 ± 1.2) (p =.017). Probing pocket depth (PPD) reduction (4.0 ± 0.7 vs. 3.3 ± 1.4 mm) was also near to statistical significance (p =.051). Also, more sites achieved successful composite outcome measure (final PPD ≤ 4 mm and CAL gain ≥3 mm) for the regenerative treatment in the flapless + EMD group (82.6% vs. 52.2%; p =.028). In terms of radiographic outcomes, EMD yielded a greater defect bone fill than flapless treatment alone (3.0 ± 1.0 mm vs. 1.8 ± 1.5 mm; p <.001). Conclusions: The additional application of EMD during the flapless procedure for intrabony defects slightly improved clinical and radiographic outcomes. ClinicalTrials.gov identification number: NCT05456555. [ABSTRACT FROM AUTHOR]

Background: Periodontal tissue loss is the main reason for tooth mobility and loss caused by periodontal disease. Dental follicle stem cells (DFSCs) have significant therapeutic potential in periodontal regeneration, which maybe mainly depends on their potent immunomodulatory capacity. Consequently, this study aims to elucidate the impact of implanted xenogenous DFSCs on innate immune responses during early and late stages in the periodontal defect repair period. Methods: To trace and investigate the immunomodulation mechanisms of DFSCs in vivo, DFSCs were engineered (E-DFSCs) using lentiviral vectors expressing CD63-enhanced green fluorescent protein (CD63-EGFP) and β-Actin-mCherry protein (ACTB-mCherry) to exhibit green and red fluorescence. The biological characteristics and functions of E-DFSCs were verified by proliferation, differentiation, and co-culture experiments in vitro. In vivo, the periodontal regeneration capacity of E-DFSCs was detected by implantation of murine periodontal defect model, and the response of innate immune cells was detected at the 1st, 3rd, and 5th days (early stage) and 4th week (late stage) after implantation. Results: In vitro assessments showed that E-DFSCs retain similar properties to their non-engineered counterparts but exhibit enhanced macrophage immunomodulation capability. In mice models, four-week micro-CT and histological evaluations indicated that E-DFSCs have equivalent efficiency to DFSCs in periodontal defect regeneration. At the early stage of repair in mice periodontal defect, fluorescence tracking showed that implanted E-DFSCs might primarily activate endogenous cells through direct contact and indirect actions, and most of these cells are myeloperoxidase-positive neutrophils. Additionally, compared with the control group, the neutrophilic infiltration and conversion of N2-type were significantly increased in the E-DFSC group. At the late stage of defect regeneration, more M2-type macrophages, fewer TRAP + osteoclasts, and an upregulated OPG/RANKL ratio were detected in the E-DFSC group compared to the control group, which indicated that immune balance tilts towards healing and bone formation. Conclusion: The xenogenous implanted DFSCs can induce the N2 phenotype of neutrophils in the early stage, which can activate the innate immune mechanism of the host to promote periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

The periodontium is a complex hierarchical structure composed of alveolar bone, periodontal ligament, cementum, and gingiva. Periodontitis is an inflammatory disease that damages and destroys the periodontal tissues supporting the tooth. Periodontal therapies aim to regenerate the lost tissues, yet current treatments lack the integration of multiple structural/biochemical instructive cues to induce a coordinated regeneration, which leads to limited clinical outcomes. Hierarchical biomaterial scaffolds offer the opportunity to recreate the organization and architecture of the periodontium with distinct compartments, providing structural biomimicry that facilitates periodontal regeneration. Various scaffolds have been fabricated and tested preclinically, showing positive regenerative results. This review provides an overview of the recent research on hierarchical scaffolds for periodontal tissue engineering (TE). First, the hierarchical structure of the periodontium is described, covering the limitations of the current treatments used for periodontal regeneration and presenting alternative therapeutic strategies, including scaffolds and biochemical factors. Recent research regarding hierarchical scaffolds is highlighted and discussed, in particular, the scaffold composition, fabrication methods, and results from in vitro/in vivo studies are summarized. Finally, current challenges associated with the application of hierarchical scaffolds for periodontal TE are debated and future research directions are proposed. [ABSTRACT FROM AUTHOR]

Background: The present study aims to evaluate and compare the effects of 1% melatonin gel plus platelet‐rich fibrin (PRF) and PRF alone in treatment of furcation defects, clinically and radiographically using cone‐beam computed tomography. Methods: This split‐mouth clinical trial included 23 patients with 46 bilateral Grade II furcation defects in first or second maxillary or mandibular molars. Control group was treated with PRF alone while the test group was treated with 1% melatonin gel and PRF. Clinical attachment level (CAL) and horizontal probing depth (HPD) were primary outcome parameters while secondary outcome parameters were pocket probing depth (PPD) and defect volume (DV) assessed at 3 and 6 months postoperatively. Results: Significantly greater mean reduction of PPD, HPD, and CAL gain was observed in test group (2.23 ± 0.41, 2.36 ± 0.68, and 2.97 ± 0.62 mm, respectively) in comparison with control group (2.83 ± 0.78, 2.85 ± 0.67, and 3.21 ± 0.86 mm, respectively) at 6 months. A significant reduction in the mean DV was exhibited radiographically in test group (1.06 ± 0.5 mm3) as compared with control group (3.94 ± 1.32 mm3) at the end of 6 months. Both the groups showed improvements in assessed parameters. Conclusions: In Grade II furcation defects the combination therapy of 1% melatonin + PRF shows a statistically significant degree of bone fill within the periodontal tissues and also better results in terms of decrease in PPD, HPD, and a greater CAL gain. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate alterations in the concentrations of matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) within gingival crevicular fluid (GCF) extracted from the intrabony periodontal defect site before and after minimally invasive regenerative surgery, with or without supplemental laser application. The surgical procedure was performed using the modified minimally invasive surgical technique (M-MIST). Methods: Thirty-eight patients, each presenting with a single vertical defect, were randomly assigned to either the test (M-MIST + Er:YAG + Nd:YAG) or the control group (M-MIST). IL-8 and MMP-9 levels (primary outcomes of the study) were assessed prior to therapy, after 2 and 4 weeks, and 6 months following the surgical procedure by means of dedicated ELISA kits. Results: Both procedures were clinically effective as evidenced by probing depth (PD) reduction and clinical attachment level (CAL) gain at the 6-month follow-up. No statistical differences were observed in the levels of MMP-9 and IL-8 between the groups at any time point assessed. The changes in the level of MMP-9 and IL-8 over time were not statistically significant in any group. IL-8 was positively correlated with MMP-9 in the control group throughout the study and in the test group 2 weeks and 6 months post-op. Conclusions: Within the limitations of this study, the additional application of Er:YAG + Nd:YAG lasers alongside the M-MIST procedure did not enhance the clinical and biochemical treatment outcomes compared to M-MIST alone. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate in vivo and in vitro the effectiveness of the use of fibroblast growth factor (FGF)-2 with carbonate apatite (CO3Ap) on periodontal healing. Periodontal defects created in the maxillary first molars in rats were treated with FGF-2, CO3Ap, FGF-2 + CO3Ap or left unfilled. Healing was evaluated using microcomputed tomography, histological, and immunohistochemical analyses. In vitro experiments were performed to assess cellular behaviors and the expression of osteoblastic differentiation markers in MC3T3-E1 cells. At 4 weeks, the bone volume fraction in the FGF-2 + CO3Ap group was significantly greater than that in the CO3Ap group, but there was no significant difference from the FGF-2 group. The FGF-2 + CO3Ap group demonstrated greater new bone compared with the FGF-2 or CO3Ap group. The FGF-2 + CO3Ap group showed greater levels of osteocalcin-positive cells compared with the CO3Ap group, but there was no significant difference from the FGF-2 group. In vitro, the FGF-2 + CO3Ap group exhibited a greater extent of cell attachment and more elongated cells compared with the CO3Ap group. Compared with the CO3Ap group, the FGF-2 + CO3Ap group showed significantly higher viability/proliferation, but the expressions of Runx2 and Sp7 were reduced. The results indicated that the use of FGF-2 with CO3Ap enhanced healing in the periodontal defects. FGF-2 promoted cell attachment to and proliferation on CO3Ap and regulated osteoblastic differentiation, thereby contributing to novel bone formation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the factors influencing the clinical outcomes of regenerative therapy using recombinant human fibroblast growth factor‐2 (rhFGF‐2). Background: rhFGF‐2 promotes periodontal regeneration, and identifying the factors influencing this regeneration is important for optimizing the effectiveness of rhFGF‐2. Methods and Materials: This study used a hospital information‐integrated database to identify patients who underwent periodontal regenerative therapy with rhFGF‐2. Factors included age, smoking status, diabetes mellitus (DM), periodontal inflamed surface area (PISA) at the initial visit, whether the most posterior tooth was involved or not, and preoperative radiological bone defect angle. Periodontal regenerative therapy outcomes were defined as good if radiographic bone fill ≥35% or periodontal pocket closure at 9–15 months after surgery. Bone fill rate (%) and periodontal pocket depth (mm) were also used as outcome measures. Factors were evaluated by simple regression analysis, and then the association between factors and the outcomes was determined by multivariate analysis. Results: PISA and age at the first visit did not significantly influence the success or failure of bone fill rate byrhFGF‐2. However, DM, radiographic bone defect angle, and the most posterior tooth significantly influenced the regenerative effect (success/failure in bone fill) of rhFGF‐2. The most posterior tooth was significantly associated with bone fill rate by rhFGF‐2. Examination of the association between pocket closure and factors shows that the most posterior tooth significantly influenced. The most posterior tooth and preoperative PPD were significantly associated with pocket reduction depth. For the most posterior tooth, a significantly higher bone regeneration rate (p <.05) was observed with a combination of autologous bone graft and rhFGF‐2 than with rhFGF‐2 alone, and the effect was significant in multivariate analysis. Conclusions: The radiographic bone defect angle, the involvement of most posterior teeth, and the presence of DM influenced the effectiveness of rhFGF‐2 in periodontal regeneration. However, PISA values and age at the initial visit had no significant effect. [ABSTRACT FROM AUTHOR]

Amnion-chorion membrane (ACM) has emerged as a versatile biomaterial with immense potential in various medical and dental applications, including periodontal therapy. ACM possesses unique properties, including a bioactive matrix rich in growth factors, anti-inflammatory and antibacterial attributes, and a remarkably thin, self-adherent structure. These characteristics make ACM well suited for various periodontal applications, such as intrabony defect treatment, gingival recession management, socket preservation, papillary preservation, and sinus membrane repair. This review offers comprehensive details of the properties, applications, and implications of ACM membranes in the realm of periodontal treatment. [ABSTRACT FROM AUTHOR]

Introduction: Teeth affected by periodontitis exhibit an increased mineral content and endotoxins. They do not harmonise with the neighbouring periodontal cells, whose growth is essential for periodontal regeneration. This scanning electron microscope (SEM) study evaluated and compared the in vitro effects of different citric acid application techniques on naturally preserved dentin slabs. Materials and Methods: Thirty-two dentinal slabs were prepared for experimentation, with one group undergoing various treatments and a control group left untreated. The citric acid solution, with a pH of 1.0, was meticulously prepared and used in four different application methods on the experimental group. The dentin slabs were prepared for SEM evaluation, which assessed parameters such as exposed dentinal tubules, the surface area occupied by tubule orifices, the demineralised zone’s width and the exposed tubules’ morphological characteristics. Results: The data present the mean number of exposed dentinal tubules for different application techniques and the width of the demineralised zone. While the f-test did not show significant differences in the width of the demineralised zone, the number of exposed dentinal tubules varied significantly. Immersion treatment resulted in the highest number of open tubules, followed by cotton pellet placement and brushing. Conclusions: The study suggests that in periodontal regenerative procedures, passive citric acid application may be more effective than vigorous methods like burnishing for exposing inter-tubular fibrils and dentinal openings. [ABSTRACT FROM AUTHOR]

Objectives: To assess gingival crevicular fluid (GCF) levels of inflammatory and bone remodelling related biomarkers following transplantation of a tissue-engineered biocomplex into intrabony defects at several time-points over 12-months. Materials and methods: Group-A (n = 9) received the Minimal Access Flap (MAF) surgical technique combined with a biocomplex of autologous clinical-grade alveolar bone-marrow mesenchymal stem cells in collagen scaffolds enriched with an autologous fibrin/platelet lysate (aFPL). Group-B (n = 10) received the MAF surgery, with collagen scaffolds enriched with aFPL and Group-C (n = 8) received the MAF surgery alone. GCF was collected from the osseous defects of subjects via paper strips/30 sec at baseline, 6-weeks, 3-, 6-, 9-, 12-months post-surgery. Levels of inflammatory and bone remodelling-related biomarkers in GCF were determined by ELISA. Results: Group-A demonstrated significantly higher GCF levels of BMP-7 at 6–9 months than baseline, with gradually decreasing levels of pro-inflammatory and pro-osteoclastogenic markers (TNF-α, RANKL) over the study-period; and an overall decrease in the RANKL/OPG ratio at 9–12 months than baseline (all p < 0.001). In comparison, only modest interim changes were observed in Groups-B and -C. Conclusions: At the protein level, the approach of MAF and biocomplex transplantation provided greater tissue regeneration potential as cell-based therapy appeared to modulate inflammation and bone remodelling in residual periodontal defects. Clinical relevance: Transplantation of a tissue engineered construct into periodontal intrabony defects demonstrated a biochemical pattern for inflammatory control and tissue regeneration over 12-months compared to the control treatments. Understanding the biological healing events of stem cell transplantation may facilitate the design of novel treatment strategies. Clinical database registration: ClinicalTrials.gov ID: NCT02449005. [ABSTRACT FROM AUTHOR]

Biologic modifiers are materials or proteins and factors that have the potential to alter the host tissue so as to stimulate or regulate the wound healing process. Classic examples of biologic modifiers are growth factors. Bioengineered materials are widely utilized due to their biocompatibility and degradability, as well as their moisturizing and antibacterial properties. One field of their application in medicine is to treat wounds by promoting tissue regeneration and improving wound healing. In addition to creating a physical and chemical barrier against primary infection, the mechanical stability of the porous structure of biomaterials provides an extracellular matrix (ECM)-like niche for cells. Growth factors are polypeptide molecules that control the growth, differentiation, and metabolism of cells during each of the three phases of wound healing. They are present throughout the body in only minute concentrations yet exert a powerful local influence on wound repair. They interact with specific receptors in the cell surface, leading to specific responses determined by the receptor-mediated signal transduction pathways within the target cells. Growth factors (GFs) and cytokines, which are secreted by the cells, are essential parts of the complex process of tissue regeneration and wound healing. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Thermosensitive hydrogels are now among the most commonly used biomaterials in tissue engineering. Due to their unique characteristics, this review aimed to evaluate the suitability of thermosensitive hydrogels in periodontal regeneration. Material and Methods PubMed, Scopus, and Web of Science databases were searched until March 25, 2024, to retrieve relevant articles. The eligibility criteria for the included studies were determined by the designed PICO elements. Results from each included study were extracted, focusing on the three main areas: thermosensitivity, cellular characteristics, and in vivo characteristics. Results Nineteen studies were included in our study. The thermosensitivity assessment of the hydrogels indicated a range of sol–gel transition times from 40 s to 20 min based on the type of polymers and the fabrication process. The cellular characterization was assessed based on three main cellular behaviors: cellular viability/proliferation, differentiation, and migration. The in vivo characterization was performed based on two main approaches: radiographic and histologic evaluation. Conclusions The results indicated that the addition of bioactive agents could enhance the in vivo efficacy of thermosensitive hydrogels in periodontal regeneration through three main areas: antimicrobial, anti‐inflammatory, and regenerative effects.

Periodontal disease (PD) is a chronic inflammatory condition that affects the teeth and their supporting tissues, ultimately culminating in tooth loss. Currently, treatment modalities, such as systemic and local administration of antibiotics, serve to mitigate the progression of inflammation yet fall short in restoring the original anatomical structure and physiological function of periodontal tissues. Biocompatible material-based tissue engineering seems to be a promising therapeutic strategy for treating PD. Collagen, a component of the extracellular matrix commonly used for tissue engineering, has been regarded as a promising biogenic material for tissue regeneration owing to its high cell-activating and biocompatible properties. The structural and chemical similarities between collagen and components of the oral tissue extracellular matrix render it a promising candidate for dental regeneration. This review explored the properties of collagen and its current applications in periodontal regeneration. We also discussed the recent progression in collagen therapies and preparation techniques. The review also scrutinizes the pros and cons associated with the application of collagen-based biomaterials in PD treatment, aiming to pave the way for future applications of collagen-based biomaterials in the management of PD.

The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of the use of systemic antibiotics in regenerative periodontal surgery for treating teeth affected by periodontitis. Data sources: Electronic (MEDLINE, EMBASE, LILACS, Scopus, and Cochrane) and manual literature searches for human randomized controlled trial studies published up to November 2022 were conducted by two reviewers. Meta-analysis was performed to assess probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain in groups receiving systemic antibiotics compared to those not receiving systemic antibiotics. A total of eight studies were included. While treated sites were intrabony defects in six papers, two studies focused on furcation defects. For intrabony defects, the weighted mean difference (WMD) of 0.30 mm (95% CI −0.18 to 0.78) and 0.27 mm (95% CI −0.13 to 0.66) was calculated for PPD reduction and CAL gain, respectively. The differences between antibiotics and non-antibiotics groups for PPD and CAL were not statistically significant. Quantitative analysis could not be performed for furcation defects due to the limited number of studies. However, regardless of the membrane type selection, the existing evidence indicated that antibiotics did not lead to superior clinical outcomes for furcation defects at 9 to 12 months after the regenerative procedures. Conclusion: Based on this meta-analysis study’s findings, the use of adjunct systemic antibiotics in regenerative periodontal surgery did not appear to achieve more favorable clinical outcomes. Thus, the use of adjunct systemic antibiotics as part of the regenerative periodontal therapy might not be justifiable and should be reconsidered. [ABSTRACT FROM AUTHOR]

Introduction: For deep intrabony defects or Class II furcation involvements (FI), periodontal tissue regenerative therapy combined with bone graft materials and a barrier membrane is recommended. The objective of this study was to assess the safety and efficacy of using carbonate apatite (CO3Ap) granules and absorbable poly(lactic acid/caprolactone) (PLCL) membranes for periodontal regeneration in the treatment of intrabony defects and mandibular Class II FI. Methods: This prospective pilot clinical study, conducted at a single center with a single-arm design, aimed to assess the safety and efficacy of CO3Ap and PLCL membranes in patients with periodontitis. A total of 9 patients with 10 teeth, including seven deep intrabony defects and three Class II FI, were treated with CO3Ap granules and PLCL membranes. Clinical parameters such as probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), tooth mobility (Mo), Plaque Index (PI), and Gingival Index (GI) were assessed at baseline, 6 and 12 months post-surgery. Radiographic analysis was performed using dental X-rays and cone beam computed tomography (CBCT) images taken at baseline, 6, and 12 months post-surgery. Results: Postoperative healing was uneventful in most of the cases. In some cases, membrane exposures were observed. However, there were no signs of inflammation, such as abnormal bleeding, pain, swelling, or pus. These exposures eventually healed well in the end. The mean reductions in PPD at 6 and 12 months were 4.5 ± 1.6 mm and 4.9 ± 1.4 mm, respectively, while the mean gains in CAL were 4.4 ± 1.7 mm at 6 months and 4.6 ± 1.2 mm at 12 months. Radiographic analysis showed improvements in linear bone height within intrabony defects and in the vertical subclassification of FI in Class II FI. Conclusions: Despite the limitations of this study, periodontal regenerative therapy using CO3Ap granules and a PLCL membrane demonstrated promising clinical safety and efficacy for treating intrabony defects and mandibular Class II furcation involvement.

الملخص: التهاب اللثة هو مرض فموي منتشر يضر بالأنسجة الصلبة والناعمة في اللثة، مما يؤدي إلى تخفيف الأسنان وإزالتها في نهاية المطاف. العلاجات السريرية الحالية لها حدود في تحقيق تجديد كامل لأنسجة اللثة. لقد جذبت الخلايا الجذعية الوسيطة الاهتمام بسبب خصائصها الفريدة وإمكاناتها كعلاج جديد واعد لالتهاب اللثة. تشير الأبحاث إلى أن دور الخلايا الجذعية الوسيطة في الطب التجديدي يحدث في المقام الأول من خلال مسار نظير الصماوي، والذي يتضمن إطلاق جزيئات محاطة بالدهون تسمى الحويصلات خارج الخلية المتوفرة بكثرة في المركبات النشطة بيولوجيا. تلعب هذه الحويصلات خارج الخلية وظيفة حاسمة في التحكم في أنشطة أنسجة اللثة، وخلايا الجهاز المناعي، ومن خلال التأثير على المحيط المباشر، وبالتالي تعزيز شفاء تلف اللثة وتجديد الأنسجة. توفر الحويصلات خارج الخلية التي يتم الحصول عليها من الخلايا الجذعية الوسيطة، في شكل علاج دون استخدام الخلايا، مزايا من حيث الاستقرار، وتقليل الرفض المناعي، والاعتبارات الأخلاقية، مما يزيد من إمكاناتها كخيار متفائل للتطبيقات السريرية واسعة النطاق. تسلط هذه النظرة الموجزة الضوء على الحويصلات خارج الخلية التي تم الحصول عليها من آليات الخلايا الجذعية الوسيطة وتطبيقها السريري المحتمل في تجديد اللثة. Abstract: Periodontitis is a prevalent oral ailment that harms both hard and soft tissues of the periodontium, leading to loosening and eventual removal of the teeth. Current clinical treatments have limitations in achieving complete periodontal tissue regeneration. Mesenchymal stem cells (MSCs) have garnered attention due to their unique characteristics and potential as a promising new therapy for periodontitis. Research suggests that the role of MSCs in regenerative medicine primarily occurs through the paracrine pathway, involving the emission of particles encased by lipids called extracellular vesicles (EVs) abundant in bioactive compounds. These EVs play a vital function in controlling the activities of periodontal tissues and immune system cells, and by influencing the immediate surrounding, thus fostering the healing of periodontal damage and renewal of tissues. EVs obtained from MSCs (MSC-EVs), in the form of a cell-free treatment, offer advantages in terms of stability, reduced immune rejection, and ethical considerations, elevating their potential as a hopeful choice for broad clinical applications. This concise overview highlights the mechanisms of MSC-EVs and the possibilities they hold in clinical application for periodontal regeneration.

Objective: To evaluate the five-year results following regenerative periodontal surgery of intrabony defects using an enamel matrix derivative (EMD) in patients with different smoking status. Method and materials: The dental records of patients treated with regenerative periodontal surgery with EMD between 2001 and 2011 were screened. The clinical parameters at baseline (T0) and 6 months (T1) and 5 years (T2) after surgery were collected and analyzed in relation to patient's smoking status (smokers, former smokers, and nonsmokers). Results: A total of 71 sites were initially assessed in 38 patients. In total, 56 sites could be evaluated at T1, and 34 after 5 years (T2). At 6 months after surgery, a statistically significant mean probing pocket depth (PPD) reduction of 2.91 ± 1.60 mm and a mean clinical attachment level (CAL) gain of 1.89 ± 1.90 mm were measured. Nonsmokers revealed a greater, statistically not significant CAL gain compared to smokers (2.38 ± 2.12 mm vs 1.50 ± 1.71 mm). Although at 5 years the site-specific PPD values remained stable in nonsmokers, smokers showed an increase of 1.60 ± 2.41 mm. Conclusions: The present study provides evidence that regenerative periodontal surgery with EMD may lead to clinically relevant improvements even in smoking patients. However, the positive effect of EMD seems to be limited in time and can only partially compensate for the negative influence of smoking. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to histologically compare periodontal regeneration of one-wall intrabony defects treated with open flap debridement, β-tricalcium phosphate (β-TCP), and carbonate apatite (CO3Ap) in dogs.MethodsThe mandibular third premolars of four beagle dogs were extracted. Twelve weeks after the extraction, a one-wall bone defect of 4 mm × 5 mm (mesio-distal width × depth) was created on the distal side of the mandibular second premolar and mesial side of the fourth premolar. Each defect was randomly allocated to open flap debridement (control group), periodontal regeneration utilizing β-TCP, or CO3Ap. Eight weeks after the surgery, histologic and histometric analyses were performed.ResultsNo ankylosis, infection, or acute inflammation was observed at any of the experimental sites. Newly formed bone and cementum were observed in all experimental groups. The mineral apposition rate of the alveolar bone crest was higher in the CO3Ap group than in the control and β-TCP groups. The ratio of the new bone area was significantly higher in the CO3Ap group than in the control group (P

BACKGROUND: Cell derivative is cell-derived bioactive components, including decellularized extracellular matrix, exosome, apoptotic extracellular vesicle, and conditioned medium, has the effects on immune regulation, promoting angiogenesis, bone regeneration, ligament remodeling, and is capable of promoting stem cell chemotherapy, migration, proliferation, and adhesion. Its excellent characteristics make it a promising biomaterial for application and clinical translation in the field of periodontal tissue engineering. OBJECTIVE: To review the characteristics of cell derivatives (decellularized extracellular matrix, exosome, apoptotic extracellular vesicle, and conditioned medium) and its effect and the latest progress in the field of regenerative restoration of periodontal complex tissue structures. METHODS: We searched the articles on CNKI and PubMed databases with the search terms “regeneration, periodontal tissue, tissue engineering, decellularized matrix, exosome, apoptotic extracellular vesicle, condition medium” in Chinese and English, respectively. Finally, 76 articles were included for analysis and discussion. RESULTS AND CONCLUSION: (1) Among those four cell derivatives, the decellularized extracellular matrix has the best mechanical properties and fibrous structure, serving as a biomimetic scaffold to provide physiochemical signals and participate in mechanical signaling in periodontal tissue engineering, providing supporting effect suitable for periodontal regeneration. Recently, the development of soluble decellularized extracellular matrix bioinks has enabled the fabrication of regenerative scaffolds for personalized periodontal defects. (2) Exosomes are the simplest cell derivatives that have immunomodulatory capacity, promoting cell migration and differentiation. As a carrier, they can be used to carry target molecules to regulate periodontal regeneration, promote ligament remodeling and bone regeneration, and are suitable for periodontal tissue engineering. (3) Apoptotic vesicles generated from apoptotic cells have a strong immunomodulatory effect and can recruit stem cells and macrophages, which determine the fate of stem cells through signal transduction and can enhance immunomodulation to promote periodontal regeneration. Engineered extracellular vesicle is considered to have the potential to initiate targeted internal immunomodulation. (4) The extraction of conditioned medium is simple and completely noninvasive, which provides essential nutrients and growth factors for tissue regeneration. These components are crucial for successful periodontal regeneration. Therefore, the conditioned medium is especially suitable for studying the interactions between cells in vitro and has an important role in high-throughput detection in the future. [ABSTRACT FROM AUTHOR]

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1β, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1β and MMP-8 and -9 (p < 0.001), while IL-12 showed a direct relationship with CAL gain (p = 0.005) and PPD reduction (p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to compare clinical benefits of autologous platelet concentrate with other periodontal regenerative approaches in intrabony defects. An electronic and hand search of studies up to December 2022 was conducted. Randomized controlled trials with at least 6 months of follow‐up were identified to compare autologous platelet concentrates with enamel matrix derivative, bone graft, guided tissue regeneration, and open‐flap debridement. All approaches involved papilla preservation flap surgery. The outcomes included probing depth reduction, clinical attachment level gain, linear bone fill, and safety. A network meta‐analysis and meta‐regression were performed. Fifty‐seven studies were included in five network meta‐analyses. Autologous platelets concentrate and its adjunct treatments achieved significantly greater clinical and radiographic parameters than did open‐flap debridement, and had comparable or better performance than other regenerative treatments. Platelet‐rich fibrin showed superiority over platelet‐rich plasma in probing depth reduction at 6‐month follow‐up. Minimal pain and improved wound healing were observed in the treatments with autologous platelet concentrate. Meta‐regression showed that deeper baseline intrabony defects resulted in larger probing depth reductions, while smoking impaired the effectiveness of regenerative surgeries. Minimal invasive flap designs led to less effect of regenerative materials. Autologous platelet concentrate is a promising biomaterial in periodontal regeneration due to its convenience, safety, and biocompatibility characteristics. [ABSTRACT FROM AUTHOR]

Background: With the entire papilla preservation (EPP) technique, it is possible to perform regenerative therapy without incisions in the interdental papilla and to reduce the risk of papillary rupture. However, one limitation of the EPP is the sole access from the buccal side. Here, we present a case of periodontitis treated by the combination regenerative therapy employing the Double‐sided (buccal‐palatal) EPP (DEPP) technique, which adds a palatal vertical incision to the EPP. Methods: A patient with 1–2 wall intrabony defects received the regenerative therapy using recombinant human fibroblast growth factor (rhFGF)‐2 and carbonate apatite (CO3Ap). Using the DEPP technique, vertical incisions at buccal and palatal aspects were placed to gain adequate access to the 1–2 wall intrabony defects between #11 and #12 without incision in the interdental papilla. After debridement, rhFGF‐2 and CO3Ap were applied to the defect. Periodontal clinical parameters and radiographic images were evaluated at the first visit, following initial periodontal therapy (baseline), 6, 9, and 12 months postoperatively. Results: Wound healing was uneventful. Scarring of the incision lines was minimal. At 12 months postoperatively, probing depth reduction was 4 mm, clinical attachment gain was 4 mm, and gingival recession was not observed. An improvement in radiopacity in the previous bone defect was observed. Conclusion: The DEPP is an innovative technique that allows approaching from both the buccal and palatal sides while ensuring flap extensibility without compromising the interdental papilla. This report suggests that the combination of regenerative therapy with the DEPP may be promising in the treatment of intrabony defects. Key points: Why is this case new information?The DEPP allows a direct visual approach to a 1–2 wall intrabony defect extending from the buccal to palatal sides, and increases flap extensibility, without compromising the papilla. What are the keys to the successful management of this case?Assessment of three‐dimensional bone defect morphology is required. Computed tomography images are very useful. The flap elevation just under the interdental papilla should be carefully performed with a small excavator to avoid damage to the interdental papilla. What are the primary limitations to success in this case?Despite the addition of a palatal incision, it was not possible to obtain complete flexibility of the palatal gingiva. Caution must be taken in a case in which the distance between the interdental papilla is narrow. Even if the interdental papilla is ruptured during the operation, recovery is possible by continuing the operation and suturing the rupture at the end. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of subgingival delivery of progranulin (PGRN)/gelatin methacryloyl (GelMA) complex as an adjunct to scaling and root planing (SRP) on an experimental periodontitis dog model with Class II furcation involvement (FI). Materials and Methods: A Class II FI model was established, and the defects were divided into four treatment groups: (a) no treatment (control); (b) SRP; (c) SRP + GelMA; (d) SRP + PGRN/GelMA. Eight weeks after treatment, periodontal parameters were recorded, gingival crevicular fluid and gingival tissue were collected for ELISA and RT‐qPCR, respectively, and mandibular tissue blocks were collected for micro computed tomography (micro‐CT) scanning and hematoxylin and eosin (H&E) staining. Results: The SRP + PGRN/GelMA group showed significant improvement in all periodontal parameters compared with those in the other groups. The expression of markers related to M1 macrophage and Th17 cell significantly decreased, and the expression of markers related to M2 macrophage and Treg cell significantly increased in the SRP + PGRN/GelMA group compared with those in the other groups. The volume, quality and area of new bone and the length of new cementum in the root furcation defects of the PGRN/GelMA group were significantly increased compared to those in the other groups. Conclusions: Subgingival delivery of the PGRN/GelMA complex could be a promising non‐surgical adjunctive therapy for anti‐inflammation, immunomodulation and periodontal regeneration. [ABSTRACT FROM AUTHOR]

Periodontal Disease (PD) is one of the most common inflammatory oral diseases, affecting majority of the population who are 30 years and older. Improper treatment of periodontal disease leads to degradation of periodontal tissues, eventually leading to tooth loss. Conventional clinical therapy for PD aims at eliminating infectious sources and reducing inflammation to arrest disease progression, which cannot achieve the regeneration of lost periodontal tissues. Over the past two decades, various regenerative periodontal therapies, such as Guided Tissue Regeneration (GTR), enamel matrix derivative, bone grafts, growth factor delivery, and the combination of cells and growth factors with matrix-based scaffolds, have been developed to target the restoration of lost tooth-supporting tissues, including the periodontal ligament, alveolar bone, and cementum. This review discusses recent progress in periodontal regeneration using tissueengineering and regenerative medicine approaches. Specifically, the focus is on the advances in biomaterials and controlled drug delivery for periodontal regeneration in recent years. Special attention is given to the development of advanced bio-inspired scaffolding biomaterials and temporospatial control of multi-drug delivery for the regeneration of the cementum-periodontal ligament-alveolar bone complex. Challenges and future perspectives are presented to provide inspiration for the design and development of innovative biomaterials and delivery systems for new regenerative periodontal therapy. [ABSTRACT FROM AUTHOR]

Objective: Periodontitis is an inflammatory condition induced by subgingival bacterial dysbiosis, resulting in inflammatory‐mediated destruction of tooth‐supporting structures, potentially leading to the formation of infrabony defects. This case report describes the treatment of a patient who presented with a combination 1–2‐wall defect on tooth 21. To maintain the residual periodontal attachment and minimize esthetic consequences, a regenerative approach was performed using recombinant human platelet‐derived growth factor‐BB (rh‐PDGF‐BB) and β‐tricalcium phosphate (β‐TCP). Materials and Methods: At the time of postscaling/root planing reevaluation, a 34‐year‐old Asian male initially diagnosed with molar/incisor pattern stage III grade C periodontitis exhibited a 6‐mm residual probing depth on the mesiopalatal aspect of tooth 21. Periodontal regenerative surgery was performed using rh‐PDGF‐BB with β‐TCP, without the use of a membrane. Results: At the 1‐year follow‐up, a significant reduction in probing depth and radiographic evidence of bone fill were observed. Additionally, re‐entry surgery for implant placement at site tooth 23 confirmed bone fill in the defect on tooth 21. Conclusion: These results demonstrate the efficacy of rh‐PDGF‐BB with β‐TCP in enhancing periodontal regeneration and support its use as a treatment option when treating poorly contained infrabony defects in the esthetic zone. [ABSTRACT FROM AUTHOR]