Periodontitis is a chronic inflammatory disease that inflicts damage to periodontal tissues, leading to loss of teeth, and affects systemic health. Traditional treatments can delay inflammation, whereas regeneration of the periodontal complex (periodontal ligament, cementum, and alveolar bone) can better restore periodontal tissue function. In recent years, the regeneration of alveolar bone and the periodontal ligament has been widely reviewed although cementum has received less attention. As an avascular mineralised structure around the tooth, cementum can anchor periodontal ligament fibres to the root surface, thereby connecting teeth to alveolar bone. The supporting and stabilizing effects of cementum make its regeneration vital for restoring the functionality of the periodontal tissues. In this review, we discuss advancements in basic and clinical research appertaining to cementum regeneration. We describe the molecular mechanisms that contribute to cementum regeneration thereby providing a foundation for further basic research. Finally we summarise the clinical strategies employed for cementum regeneration, including regenerative surgery and utilisation of growth factors and stem cells.

This study investigated the effect of Selcopintide (SCPT) on periodontal regeneration using surgically created class II furcation defects in an animal model, employing both radiographical and histological evaluations.

Class II furcation defects were surgically induced in six beagle dogs. Each defect was unilaterally and randomly assigned to one of five treatment groups: (1) no treatment (control), (2) guided tissue regeneration (GTR) with a collagenated bone substitute and a collagen membrane, (3) GTR with an enamel matrix derivative (GTR/EMD), (4) GTR with 2 mg/ml SCPT (GTR/SCPT2), or (5) GTR with 4 mg/ml SCPT (GTR/SCPT4). Six weeks after initial surgery, identical procedures were performed on the contralateral area. Healing outcomes were assessed at 6 and 12 weeks through radiographic and histomorphometric analyses. The primary outcome was the length of the root surface covered by new cementum assessed histologically and the secondary outcome included other histomorphometric and radiographic healing outcomes.

Radiographically, the GTR/SCPT groups showed significantly greater new bone volume than the control group at both 6- and 12-week timepoints (p < 0.05). Histologically, specimens treated with both formulations of SCPT displayed better-organized periodontal ligaments and improved cementum formation, similar to those treated with EMD. The group with the highest concentration of SCPT (GTR/SCPT4) exhibited the greatest amount of new cementum formation.

Within the limitations of this study, both formulations of SCPT demonstrated significant regenerative potential in periodontal tissues, with outcomes comparable to those of EMD treatment, suggesting SCPT's viability as an alternative bioactive agent for periodontal regeneration in class II furcation defects.

This study suggests that SCPT could serve as a viable alternative bioactive agent for periodontal regeneration in class II furcation defect in clinical settings.

To evaluate the adjunctive effect of enamel matrix derivative (EMD) in the reconstructive surgical therapy of peri-implantitis.

Forty subjects (44 implants) affected by peri-implantitis (PPD ≥ 5 mm, positive BOP/SOP, intraosseous defect with a depth of ≥ 3 mm and width of ≤ 4 mm) were randomly allocated to one of two surgical protocols: control (access flap + bone graft + resorbable membrane) or test (access flap + bone graft + resorbable membrane + EMD). Clinical outcomes (PPD, BOP, SOP, buccal REC, and buccal KM) were assessed at baseline, 6 and 12 months after surgery. Radiographic marginal bone levels (MBL) and patient-reported outcomes (PROs) were recorded at baseline and at 12 months. Post-operative complications and Early Healing Index (EHI) scores were recorded at 2 weeks. The primary outcome was PPD change. Two composite outcomes (CO) were assessed: CO1 was defined as "implant not lost, PPD ≤ 5 mm, REC ≤ 1 mm and complete absence of BOP/SOP"; CO2 defined as CO1 but allowing for 1 site with BOP.

Four patients (four implants) were lost to follow-up. At 12 months, no implants were lost, 73% of implants presented with PPD ≤ 5 mm (control: 65.2%; test: 81.0%; p = 0.316) and PPD reduction amounted to 4.0 ± 1.7 and 4.3 ± 2.4 mm in control and test groups, respectively (p = 0.105). No significant differences in terms of clinical, radiographic, composite and PROs were observed between groups. No significant differences in EHI scores were found at 2 weeks between groups.

This study failed to demonstrate any benefit of the adjunctive use of EMD in the reconstructive surgical therapy of peri-implantitis.

ISRCTN18159776 (https://doi.org/10.1186/ISRCTN18159776).

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.

Silk fibroin (SF) is a biomaterial derived from the cocoon of the mulberry silkworm. This study aimed to assess the capacity of SF matrices biologized with injectable platelet-rich fibrin (iPRF) or enamel matrix protein (EMP) to modulate angiogenesis and immune response in the chorioallantoic membrane (CAM) assay.

300 eggs were divided into the following groups: CM + NaCl, CM + iPRF, CM + EMP, SF + NaCl, SF + iPRF, and SF + EMP. Matrices were applied to the CAM on embryonic development day (EDD) 7 after rehydration. Angiogenesis, represented by vascularized area, vessel density, and vessel junctions, was evaluated on EDD 10, 12, and 14. Additionally, gene expression of HIF-1ɑ, VEGF, MMP-13, and NOS2 was assessed via quantitative polymerase chain reaction (qPCR) on EDD 11 and 14.

The number of vascularized specimens was notably higher in SF matrices regardless of the treatment applied, while in the CM group, only matrices biofunctionalized with iPRF demonstrated vascularization. On EDD 14, the CM + iPRF group exhibited the highest values for total vascularized area (CM + iPRF: 57.52%, SF + iPRF: 21.87%, p < 0.001), vessel density (CM + iPRF: 0.0067 μm/µm2, SF + iPRF: 0.0032 μm/µm2, p = 0.002), number of vessel junctions (CM + iPRF: 14.45, SF + iPRF: 4.82, p = 0.001). Gene expressions displayed high data variability and no significant differences between the groups.

Biofunctionalization with iPRF in CM leads to a high vascularization rate probably through their capability of retaining higher liquid volumes, suggesting improved intraoral wound healing after guided tissue regeneration (GTR). Despite biofunctionalization, SF matrices exhibit a high vascularization, indicating SF as a promising material for GTR.

Background: Periodontitis is characterized as a change in the total periodontal tissues that includes tissue loss, as evidenced by clinical loss of attachment, and radiographically determined alveolar bone loss, periodontal pockets, and gingival bleeding. Objectives: The aim of this study was to observe and analyze recent information from the literature on the effect of enamel matrix derivative proteins on the bony defects caused by periodontitis. Methods: Through using two major online databases and search engines, the literature was manually searched for papers published until May 2024. To find relevant studies, this research utilized a combination of target keywords, and the reference lists of manuscripts that were chosen for inclusion in this study were checked and analyzed in tabular form, enabling the collection and comparison of data. Results: According to the results, the average value of the probing depth gained was 4 mm for the EMD™ alone and 4.25 mm for the EMD combined with surgical techniques such as open-flap techniques, platelet derivatives, and growth factors. In regard to clinical attachment level (CAL) gaining, average values of 3.6 mm in EMD™ alone and 3.86 mm with EMD™ combined with other techniques were observed. Conclusions: It can be concluded that the healing propensity depends on the morphological structure of the bone defect represented by the wall stage, and there is a certain coherence and correlation between the values of probing depth (PD) and clinical attachment level (CAL), whether for the use of EMD alone or its use in combination with other materials.

Background: The aim of this study was to evaluate the clinical and radiological efficacy of minimally invasive surgical techniques for infraosseous defects by evaluating the effects of Emdogain (EMD) applied alone or with a xenograft, with a follow-up period of one year. Methods: Forty patients with a combined total of forty-eight intraosseous defects participated in the research. Of these, 20 participants were treated with EMD (group 1), and 28 were treated with EMD and a xenograft (group 2). The clinical measurements probing depth (PD), recession (REC), and clinical attachment level (CAL) were assessed at six sites on the tooth. Additionally, the following intraoperative clinical measurements were taken: (1) distance from the cementoenamel junction (CEJ) to the bottom of the defect (CEJ-BD) and (2) distance from the CEJ to the most coronal extension of the interproximal bone crest (CEJ-BC). The infraosseous component of the defect was defined as INTRA = (CEJ-BD) - (CEJ-BC). Results: In comparison with the baseline, both treatment options showed statistically significant improvements in reducing PD and increasing CAL. The reduction in PD was 3.25 ± 0.786 mm for group 1 and 3.29 ± 1.013 mm for group 2. In terms of CAL gain, group 1 recorded a value of 4.65 ± 1.387 mm, compared with 5.07 ± 1.631 mm in group 2. Both groups showed a noticeable increase in radiographic bone filler, with an average of 69.85 ± 17.773%. Conclusions: The two regeneration techniques were both effective for the treatment of deep intraosseous defects, encouraging more substantial filling compared with preoperative levels.

Gingival recessions are vastly prevalent among the general population. With regards to their treatment, recent advancements in periodontal and microsurgical procedures, focusing on minimal invasiveness and patient-centered therapies, have propelled a shift in their contemporary treatment, highlighting the field of biologics and bioactive mediators. Among different classes and types of biologics, autologous platelet concentrates (APCs), also referred to as autologous blood-derived products, are commonly used and preferred among many clinicians. These are essentially obtained via venipuncture (intravenous access) followed by centrifugation, for which numerous protocols and preparation methods have been used, leading to varieties of blood-derived products. In this review, via a systematic search, we explored the efficacy of the different utilized preparation methods and centrifugation protocols of APCs (e.g., platelet-rich plasma (PRP), platelet-rich fibrin (PRF), leucocyte-PRF, advanced-PRF, concentrated growth factor (CGF), etc.) for the treatment of type 1 gingival recessions (RT1, without interproximal attachment loss or noticeable tooth displacement), as well as their effectiveness relative to a common control (treatment with flap advancement alone without any additional material). Based on the available literature from randomized trials found in our systematic search, we observed that utilization of PRF can significantly enhance treatment outcomes when performing a coronally advanced flap, in terms of the amount of root coverage. The improvement in root coverage was further enhanced in the presence of baseline keratinized tissue width, and with an increasing relative magnitude (the more the baseline keratinized tissue width, the better the root coverage outcomes when using PRF). The efficacy of these products needs to be further explored with different graft substitutes and matrices, as well as relative to other commonly applied biologics, through well-conducted and adequately-powered randomized clinical trials.

Platelet-rich fibrin (PRF) and Enamel Matrix Derivatives (EMD) can support the local regenerative events in periodontal defects. There is reason to suggest that PRF and EMD exert part of their activity by targeting the blood-derived cells accumulating in the early wound healing blastema. However, the impact of PRF and EMD on blood cell response remains to be discovered. To this aim, we have exposed human peripheral blood mononucleated cells (PBMCs) to PRF lysates prepared by a swing-out rotor and EMD, followed by bulk RNA sequencing. A total of 111 and 8 genes are up- and down-regulated by PRF under the premise of an at least log2 two-fold change and a minus log10 significance level of two, respectively. Representative is a characteristic IFN response indicated by various human leukocyte antigens (HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, HLA-DRB5), gamma Fc receptors (FCGR1A, FCGR1B, FCGR3B), chemokines (CXCL9-11), and calprotectin (S100A8/9 and S100A12), complement (C1QA/B, C2) and interferon-induced guanylate-binding proteins (GBP1, GBP5). With EMD, 67 and 29 genes are up- and down-regulated, respectively. Characteristic of the upregulated genes are tensins (TNS1 and TNS3). Among the genes downregulated by EMD were epsilon Fc receptors (FCER1A; FCER2), Fc receptor-like proteins (FCRL1, FCRL3) and CX3CR1. Genes commonly upregulated by PRF and EMD were most noticeably NXPH4 and MN1, as well as FN1, MMP14, MERTK, and AXL. Our findings suggest that PRF provokes an inflammatory response, while EMD dampens IgE signaling in peripheral mononucleated blood cells.

Various surgical techniques have recently been developed for periodontal tissue regeneration, especially those do not involve any incisions in the interdental papillae at the regeneration site. These techniques have significant advantages for obtaining clinical attachment gain with least amount of gingival recession, however, may also have disadvantages such as limited field of surgical view, difficulty in debridement, and limited access only from the buccal side. This case report addresses a 2-year follow-up with a novel surgical approach to achieve periodontal regeneration that overcomes these limitations: the flexible tunnel technique (FTT).

In a 66-year-old patient, in an enclosing infrabony defect extending to the root apex on the palatal side, which appeared to be an endodontic-periodontal lesion on tooth #5, four vertical incisions and a periosteal releasing incision were performed in order to make the interdental papillae easier to translocate over the abutment teeth, which led to obtain clearer operative field. After debridement, the enamel matrix derivative was applied to the root surface and the infrabony defect was filled with deproteinized bovine bone mineral. The flaps were relocated, and simple interrupted sutures were performed.

One year later, pocket closure and improvement of bone defects were observed without gingival recession. After confirmation with improved mobility, a full zirconia crown was placed. During 2-year follow-up, periodontal tissue was maintained well without any complication.

The FTT can be used to approach endodontic-periodontal lesions and infrabony defects extending to the root apex without incision of the interdental papillae.

A more accessible tunnel technique can be performed by using four vertical incisions. If the tooth is abutment, interdental papillae can be flexible to translocate due to this tunnel technique with vertical incisions. Ensuring root surface debridement, application of regenerative materials, and wound stability are the keys to this regenerative procedure. The patient needs to understand the risks associated with the proposed periodontal regenerative surgery and the prognosis of tooth.

Various surgical techniques have been developed recently to help regenerate the tissues that support teeth, especially methods that avoid making cuts in the gum tissue between the teeth at the treatment site. However, these techniques may have some drawbacks, such as limited visibility during surgery, difficulty cleaning the area, and access only from the outer side of the teeth. This case report addresses a 2-year follow-up of a new surgical method aimed at overcoming these challenges: the flexible tunnel technique (FTT). In a deep bone defect extending to the tip of the tooth root on the roof side, four vertical cuts and a cut to stretch the gum were made to allow better access. After cleaning the area, an enamel matrix derivative was applied to the root surface and filled with deproteinized bovine bone mineral. The area was then closed with simple stitches. After 2 years, the pocket was closed, and the bone defect improved. The FTT may be a useful technique for restoring the support structures around teeth in deep bone defects extending to the root tip without cutting the gum tissue between the teeth.

Platelet concentrates (PCs), which are blood products that are abundant in platelets and growth factors, have become pivotal in treating maxillofacial tissue lesions due to their capacity for promoting bone and soft tissue recovery. This review will provide some recent progress of the use of platelet concentrates to treat lesions on maxillofacial tissues.

We reviewed the mechanisms by which PCs promote wound healing and tissue recovery and summarized the application of PCs in the treatment of lesions on maxillofacial tissues, including medication-related osteonecrosis of the jaw, post-extraction wound healing, implant surgery, temporomandibular joint diseases, and periodontal tissue restoration.

PC promotes the attachment and proliferation of osteoblasts, as well as the synthesis and deposition of collagen fibers by stimulating the AFK pathway and releasing growth factors and cytokines, such as secreting GFs, VEGF, TGF-β, etc. They also induce angiogenesis, inhibit bone resorption, promote the healing of soft tissues, relieve symptoms, reduce postoperative complications and maintain implant stability.

PCs may be used as an adjuvant therapy in the treatment of lesions on maxillofacial tissues. However, more studies should refine the preparation and treatment methods for platelet concentrates and establish a foundation for their extensive application.

This systematic review evaluated the effectiveness of combining enamel matrix derivative (EMD) with various bone grafts in periodontal regenerative surgery, specifically targeting intrabony defects. Randomized controlled trials with 12-month follow-ups were included. Clinical outcomes assessed included clinical attachment level, probing depth, gingival recession, and radiographic defect fill. Meta-analysis showed that adding bone grafts to EMD does not provide additional benefits in periodontal tissue examination, with improvement observed only in radiographic defect fill. Subgroup analyses examined the impact of different bone graft types, revealing that alloplastic bone grafts are effective in radiographic defect fill. The risk of bias assessment indicated a moderate risk across studies, with challenges in blinding owing to the nature of the surgical treatment. Furthermore, a minimal intervention surgical approach may not require additional bone grafts for optimal periodontal regeneration. These findings contribute to the ongoing dialogue in the field and guide clinicians toward evidence-based decisions for optimal periodontal outcomes, emphasizing the judicious use of bone grafts.

An efficient therapeutic strategy for patients with replanted teeth has been extremely challenging because complete displacement of the teeth is inevitably accompanied by severe damage to periodontal tissue. Enamel matrix derivative (EMD) shows promise for periodontal regeneration, but its effects on replanted teeth remain unknown. This study systematically summarized the biological basis of EMD in replantation dental therapy and assessed its effect on clinical prognosis.

Potential studies were searched via the Cochrane Library, Web of Science and PubMed databases from inception to November 23, 2023.

A total of 329 patients with 375 replanted teeth met the inclusion criteria. Our pooling results indicated that EMD did not provide a numerical advantage for restoring normal PDL healing in replanted teeth (RR=0.38, P=0.161). A significantly lower extraction risk was observed in EMD-treated group than non-EMD-treated group (RR=0.47, P=0.001). Moreover, the survival rate of replanted teeth with root resorption was significantly increased by the application of EMD (RR=2.21, P=0.017). Although the pooled outcomes suggested increased incidence of surface resorption (RR=1.19, P=0.730) and decreased risk of inflammation resorption (RR=0.68, P=0.560) among replanted teeth with resorption in the EMD-treated group, neither difference was statistically significant.

For patients with replanted teeth, EMD treatment may not result in a numerical increase in normal PDL healing. However, as a biological regulator, EMD may arrest the progression of resorption, thus reducing the risk of extraction in the early stage. Well-designed randomized trials are required to validate these results due to the poor quality of evidence.

Reduced alveolar ridge volume is an often consequence after tooth loss, compromising implant placement and prosthetic rehabilitation. The digital customization of bone block allografts (BBA) is an alternative that incorporates advantages such as intimate contact with the recipient bed, increasing graft stability and reduced surgical time. In addition, enamel matrix derivate (EMD) has attracted interest for its effect on osteogenic gene expression and cell adhesion; few studies have focused on the benefits of bone regeneration with EMD. The aim of this case report is to present the reconstruction of a severely atrophic alveolar ridge defect with a digitally customized bone block allograft (CBBA) in combination with EMD as an adjuvant for bone regeneration and soft tissue healing.

Initially, the digital planning and manufacture of the BBA was performed based on an initial cone beam computed tomography (CBCT) scan. EMD was applied to the recipient site and to the CBBA before graft fixation. After 6 months, bone biopsies were obtained on re-entry surgery for prosthetically guided implant placement.

Clinically, bone block showed good integration with the adjacent tissue and no signs of rejection or necrosis were found. On the histological evaluation, new bone was observed in intimate contact with the allograft and showed viable osteocytes and osteoblasts along its entire length. Residual allograft particles were observed to be highly osteoconductive.

According to the clinical and histological results presented, the digital customization of the BBA allows an ideal graft fit to the recipient bed with excellent results in bone regeneration.

Context A vast body of published literature examines and evaluates the properties of bone restorative materials in combination with other biomaterials or as stand-alone applications. If we exclude the studies investigating the effectiveness of regenerative therapy with enamel matrix derivative (EMD), in all other cases, bone regenerative materials are placed on a "pedestal." Therefore, the study we have initiated covers methods whose protocol does not use bone-repair materials. The clinical and radiographic results obtained are compared to determine which of these methods is the most reliable. The most important goal we set out was to determine if periodontal regenerative therapy would be effective without the use of bone graft restorative materials.  Aim This study aimed to investigate, analyze, and compare the outcomes of four groups of patients with vertical bone defects (infrabony defects (IBDs)) who were treated using regenerative methods without the involvement of bone repair materials.  Materials and methods Forty-eight cases that fulfilled all participation criteria for the study were selected. The O'Leary plaque index (PI) and Ainamo and Bay gingival index (GI) were assessed at the reassessment visit after the Hygiene Phase, the current periodontal status was recorded, and at least one IBD was identified. Cone beam computed tomography (CBCT) was ordered, and the size of each defect was measured by three parameters. In this study, all IBDs were randomly allocated to four groups. The first category encompasses IBDs, wherein regenerative therapy utilizing autogenous, platelet-rich plasma (PRP) is implemented. The second group comprises IBDs, which undergo regenerative therapy utilizing EMD. The third category encompasses IBDs in which guided tissue regeneration (GTR) is conducted using solely a barrier membrane. The fourth group encompasses IBDs, wherein GTR utilizing a barrier membrane and PRP took place. Six months after regenerative therapy, regardless of which of the four methods was used, all patients were reassessed clinically by CBCT. Statistical methods were used to evaluate, analyze, and compare the results in the four groups. Results A statistically significant decrease in the "probing pocket depth" indication, a statistically significant clinical attachment level gain, and a statistically significant decrease in the CBCT indicators "A" and "B" were observed in all four groups of patients under study. When it comes to the CBCT indicator "C," the results for each of the four groups of patients under study fall somewhere between statistical significance and non-significant. Conclusions Regardless of the regenerative therapy technique used, all patients under examination showed improvements in imaging and clinical markers. The four patient groups' results did not differ in any way that was statistically significant.

There have been limited studies with statistically sufficient sample sizes for assessment of suitable bone defect morphology for combination therapy with enamel matrix derivative (EMD) and bone grafting. The aim of this study was to investigate the appropriate feature of intrabony defects, such as bone defect angle (DA) and the containment by bony wall, for yielding the additional benefit of bone grafting in combination with periodontal regenerative therapy using EMD.

Following periodontal regenerative therapy using EMD with or without autologous bone grafting, 282 intrabony defects of 177 participants were maintained for 3 years. Multilevel linear regression analysis was performed to evaluate the radiographic bony defect depth (RBD) reduction after adjusting for confounders.

The baseline parameters, except for the proportion of contained bony defects and tooth mobility, did not differ significantly between the groups with and without bone grafts. There was no significant difference in the improvement of clinical parameters between the groups. The 1- and 3-year reduction of RBD showed significant inverse correlations with preoperative DA only in the group without bone graft. Furthermore, multivariate analysis showed a significant interaction between DA at baseline ≥40° and adjunctive bone grafting in the reduction of RBD, regardless of the number of bony walls.

Adjunctive autologous bone grafting with enamel matrix derivative might be significantly beneficial for defect depth improvement in the case of DA at baseline ≥40°.

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.

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.

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).

The additional application of EMD during the flapless procedure for intrabony defects slightly improved clinical and radiographic outcomes.

gov identification number: NCT05456555.

The suppressive effect of bisphosphonates (BPs) on bone metabolism is considered to be a major cause of medication-related osteonecrosis of the jaw (MRONJ). Enamel matrix derivative (EMD) stimulates and activates growth factors, leading to the regeneration of periodontal tissues. In this study, we aimed to explore the potential of EMD in reversing the detrimental effects of BPs on human fetal osteoblasts (hFOBs) and osteosarcoma-derived immature osteoblasts (MG63s) by assessing cell viability, apoptosis, migration, gene expression, and protein synthesis. While the suppressive effect of zoledronate (Zol) on cell viability and migration was observed, the addition of EMD significantly mitigated this effect and enhanced cell viability and migration. Furthermore, an increased apoptosis rate induced by Zol was decreased with the addition of EMD. The decreased gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and the receptor activator of nuclear factors kappa-B ligand (RANKL) caused by BP treatment was reversed by the co-addition of EMD to hFOB cells. This trend was also observed for ALP and bone sialoprotein (BSP) levels in MG63 cells. Furthermore, suppressed protein levels of OC, macrophage colony-stimulating factor (M-CSF), BSP, and type 1 collagen (COL1) were recovered following the addition of EMD. This finding suggests that EMD could mitigate the effects of BPs, resulting in the recovery of cell survival, migration, and gene and protein expression. However, the behavior of the osteoblasts was not fully restored, and further studies are necessary to confirm their effects at the cellular level and to assess their clinical usefulness in vivo for the prevention and treatment of MRONJ.

This study aims to evaluate the influence of the additional use of enamel matrix derivate (EMD) in the treatment of gingival recession defects using a coronally advanced flap (CAF) and a xenogeneic dermal matrix (XDM) by means of digital and clinical assessment methods. In this prospective randomized controlled study, recession height and area, width and thickness of keratinized gingiva, pocket probing depth, and clinical attachment levels were measured at the baseline and followed up for one year. Fifteen patients (n = 15) with 24 gingival recession defects were treated between 2019 and 2021. On average, the digitally assessed root coverage of the control group (CAF + XDM) was not significantly different compared to the test group (CAF + XDM + EMD), with 69 ± 28% and 36 ± 32%, respectively (p = 0.094). One year postoperatively, there were no differences found regarding keratinized tissue width (KTW) between the control group and test group (p = 0.690). However, the control group showed superior results in the thickness of keratinized gingiva (p = 0.044). The present study showed that there were no statistically significant differences in the root coverage results in the CAF + XDM + EMD group compared to the CAF + XDM group. The adjunctive use of EMD to a CAF and XDM in the treatment of gingival recession defects does not appear to have any clinical benefit.

Regenerative dentistry aims to enhance the structure and function of oral tissues and organs. Modern tissue engineering harnesses cell and gene-based therapies to advance traditional treatment approaches. Studies have demonstrated the potential of mesenchymal stem cells (MSCs) in regenerative dentistry, with some progressing to clinical trials. This review comprehensively examines animal studies that have utilized MSCs for various therapeutic applications. Additionally, it seeks to bridge the gap between related findings and the practical implementation of MSC therapies, offering insights into the challenges and translational aspects involved in transitioning from preclinical research to clinical applications.

To achieve this objective, we have focused on the protocols and achievements related to pulp-dentin, alveolar bone, and periodontal regeneration using dental-derived MSCs in both animal and clinical studies. Various types of MSCs, including dental-derived cells, bone-marrow stem cells, and umbilical cord stem cells, have been employed in root canals, periodontal defects, socket preservation, and sinus lift procedures. Results of such include significant hard tissue reconstruction, functional pulp regeneration, root elongation, periodontal ligament formation, and cementum deposition. However, cell-based treatments for tooth and periodontium regeneration are still in early stages. The increasing demand for stem cell therapies in personalized medicine underscores the need for scientists and responsible organizations to develop standardized treatment protocols that adhere to good manufacturing practices, ensuring high reproducibility, safety, and cost-efficiency.

Cell therapy in regenerative dentistry represents a growing industry with substantial benefits and unique challenges as it strives to establish sustainable, long-term, and effective oral tissue regeneration solutions.

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.

Dentin matrix extracted protein (DMEP) is a mixture of proteins extracted from the organic matrix of a natural demineralized dentin matrix that is rich in a variety of growth factors. However, the effect of DMEP on cartilage regeneration is unclear. The aim of this study was to investigate the efficacy of DMEP extracted via a novel alkali conditioning method in promoting cartilage regeneration.

Alkali-extracted DMEP (a-DMEP) was obtained from human dentin fragments using pH 10 bicarbonate buffer. The concentration of chondrogenesis-related growth factors in a-DMEP was measured via enzyme-linked immunosorbent assay (ELISA). Human bone marrow mesenchymal stem cells (hBMMSCs) in pellet form were induced with a-DMEP. Alcian blue and Safranin O staining were performed to detect cartilage matrix formation, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess chondrogenic-related gene expression in the pellets. Rabbit articular osteochondral defects were implanted with collagen and a-DMEP. Cartilage regeneration was assessed with histological staining 4 weeks after surgery.

Compared with traditional neutral-extracted DMEP, a-DMEP significantly increased the levels of transforming growth factor beta 1(TGF-β1), insulin-like growth factor-1(IGF-1) and basic fibroblast growth factor (bFGF). After coculture with hBMMSC pellets, a-DMEP significantly promoted the expression of the collagen type II alpha 1(COL2A1) and aggrecan (ACAN) genes and the formation of cartilage extracellular matrix in cell pellets. Moreover, compared with equivalent amounts of exogenous human recombinant TGF-β1, a-DMEP had a stronger chondrogenic ability. In vivo, a-DMEP induced osteochondral regeneration with hyaline cartilage-like structures.

Our results showed that a-DMEP, a compound of various proteins derived from natural tissues, is a promising material for cartilage repair and regeneration.

Particulate bovine bone substitutes (BS) are commonly used in oral regeneration. However, more literature is needed focusing on comparative analyses among various particulate bovine BS. This study evaluates pre-clinical and clinical data of different particulate bovine BS in oral regeneration.

A narrative review was conducted by screening the PubMed database Included in the review were pre-clinical and clinical studies until 2024 comparing a minimum of two distinct particulate bovine BS. In addition to examining general data concerning manufacturing and treatment processes, biological safety, physical and chemical characteristics, and graft resorption, particular emphasis was placed on assessing pre-clinical and clinical data related to ridge preservation, sinus floor elevation, peri-implant defects, and various forms of alveolar ridge augmentation utilizing particulate bovine BS.

Various treatment temperatures ranging from 300 to 1,250 °C and the employment of chemical cleaning steps were identified for the manufacturing process of particulate bovine BS deemed to possess biosecurity. A notable heterogeneity was observed in the physical and chemical characteristics of particulate bovine BS, with minimal or negligible graft resorption. Variations were evident in particle and pore sizes and the porosity of particulate bovine BS. Pre-clinical assessments noted a marginal inclination towards favorable outcomes for particulate bovine BS subjected to higher treatment temperatures. However, clinical data are insufficient. No distinctions were observed regarding ridge preservation, while slight advantages were noted for high-temperature treated particulate bovine BS in sinus floor elevation.

Subtle variances in both pre-clinical and clinical outcomes were observed in across various particulate bovine BS. Due to inadequate data, numerous considerations related to diverse particulate bovine BS, including peri-implant defects, must be more conclusive. Additional clinical studies are imperative to address these knowledge gaps effectively.

Periodontitis, a prevalent inflammatory condition, affects the supporting structures of teeth, leading to significant oral health challenges. Traditional treatments have primarily focused on mechanical debridement, antimicrobial therapy, and surgery, which often fail to restore lost periodontal structures. Emerging as a novel approach in regenerative medicine, extracellular vesicle (EV) therapy, including exosomes, leverages nano-sized vesicles known for facilitating intercellular communication and modulating physiological and pathological processes. This study is a proof-of-concept type that evaluates the clinical efficacy of EV therapy as a non-surgical treatment for stage I-III periodontitis, focusing on its anti-inflammatory and regenerative potential. The research involved seven patients undergoing the therapy, and seven healthy individuals. Clinical parameters, including the plaque index, bleeding on probing, probing depth, and attachment level, were assessed alongside cytokine levels in the gingival crevicular fluid. The study found significant improvements in clinical parameters, and a marked reduction in pro-inflammatory cytokines post-treatment, matching the levels of healthy subjects, underscoring the therapy's ability to not only attenuate inflammation and enhance tissue regeneration, but also highlighting its potential in restoring periodontal health. This investigation illuminates the promising role of EV therapy in periodontal treatment, advocating for a shift towards therapies that halt disease progression and promote structural and functional restoration of periodontal tissues.

Periodontal defects present a significant challenge in dentistry, necessitating innovative solutions for comprehensive regeneration. Traditional restoration methods have inherent limitations in achieving complete and functional periodontal tissue reconstruction. Tissue engineering, a multidisciplinary approach integrating cells, biomaterials, and bioactive factors, holds tremendous promise in addressing this challenge. Central to tissue engineering strategies are scaffolds, pivotal in supporting cell behavior and orchestrating tissue regeneration. Natural and synthetic materials have been extensively explored, each offering unique advantages in terms of biocompatibility and tunable properties. The integration of growth factors and stem cells further amplifies the regenerative potential, contributing to enhanced tissue healing and functional restoration. Despite significant progress, challenges persist. Achieving the seamless integration of regenerated tissues, establishing proper vascularization, and developing biomimetic scaffolds that faithfully replicate the natural periodontal environment are ongoing research endeavors. Collaborative efforts across diverse scientific disciplines are essential to overcoming these hurdles. This comprehensive review underscores the critical need for continued research and development in tissue engineering strategies for periodontal regeneration. By addressing current challenges and fostering interdisciplinary collaborations, we can unlock the full regenerative potential, paving the way for transformative advancements in periodontal care. This research not only enhances our understanding of periodontal tissues but also offers innovative approaches that can revolutionize dental therapies, improving patient outcomes and reshaping the future of periodontal treatments.

This study compared the quality and quantity of newly formed bone in rabbits' critical-sized calvarial defects filled with enamel matrix derivative (EMD) combined with freeze-dried bone allograft (FDBA) vs FDBA alone.

A total of 24 adult male white New Zealand rabbits were included. In each rabbit, three bone defects with a diameter of 8 mm were created on the calvarium bone; the first defect was left untreated, while the second was filled with FDBA, and the third was filled with EMD + FDBA. Twelve rabbits were randomly euthanized after a month, and the remaining 2 month postsurgery. Bone sections were histologically evaluated by hematoxylin and eosin and vascular endothelial growth factor (VEGF), alkaline phosphatase (ALP), osteoprotegerin (OPG), and receptor activator of NF-kappaB (RANK) immune-histochemical staining.

An improvement in the newly formed bone percentage was found in the defects filled with EMD + FDBA in comparison with FDBA and control defects at 1 month and 2 months postsurgery. Additionally, the expression of VEGF, ALP, OPG, and RANK showed highly significant differences in the defects filled with EMD + FDBA compared to the FDBA and control ones at 1 month postsurgery (p = 0.001). Meanwhile, VEGF and ALP expression showed a significant decrease in defects filled with EMD + FDBA compared to the FDBA and control ones (p = 0.001), while OPG and RANK expression showed non-significant differences between treated groups at 2 months postsurgery.

Enamel matrix derivative combined with FDBA has a synergistic effect on bone formation and graft substitution. This combination accelerates the expression of VEGF, ALP, OPG, and RANK.

The combination of EMD and FDBA accelerates and ameliorates the quality of newly formed bone, aiding in maxillofacial reconstruction. How to cite this article: Zakri RN, Grawish ME, Mowafey B, et al. Impact of Freeze-dried Corticocancellous Bone Allograft Combined with Enamel Matrix Derivative in the Treatment of Critical-sized Calvarial Bone Defects: An Animal Study. J Contemp Dent Pract 2024;25(5):424-431.

Periodontitis is a dysbiosis-driven inflammatory disease affecting the tooth-supporting tissues, characterized by their progressive resorption, which can ultimately lead to tooth loss. A step-wise therapeutic approach is employed for periodontitis. After an initial behavioral and non-surgical phase, intra-bony or furcation defects may be amenable to regenerative procedures. This review discusses the regenerative technologies employed for periodontal regeneration, highlighting the current limitations and future research areas. The search, performed on the MEDLINE database, has identified the available biomaterials, including biologicals (autologous platelet concentrates, hydrogels), bone grafts (pure or putty), and membranes. Biologicals and bone grafts have been critically analyzed in terms of composition, mechanism of action, and clinical applications. Although a certain degree of periodontal regeneration is predictable in intra-bony and class II furcation defects, complete defect closure is hardly achieved. Moreover, treating class III furcation defects remains challenging. The key properties required for functional regeneration are discussed, and none of the commercially available biomaterials possess all the ideal characteristics. Therefore, research is needed to promote the advancement of more effective and targeted regenerative therapies for periodontitis. Lastly, improving the design and reporting of clinical studies is suggested by strictly adhering to the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement.

Furcation-involved teeth, commonly seen in dental practice, have a higher likelihood of needing extraction as the severity of periodontal furcation involvement increases. Studies consistently show that periodontitis in teeth with multiple roots significantly increases the risk of tooth loss, especially in the area where the furcation is involved. These furcation defects pose a major problem for dentists because of their location, accessibility issues, and the unpredictable healing process. The biggest hurdle in treating furcation defects is their irregular shape, which makes it hard to achieve complete debridement. While various treatments have been explored, non-surgical methods have not shown much success. This article comprehensively provides a review and discussion on the classification, assessment, and treatment options, including surgical and non-surgical management of furcation-involved molar teeth. Properly understanding the severity of the disease and its confounding factors and managing and treating the lesions appropriately have been shown to impart satisfactory survival rates for these teeth. Enhancing the understanding of managing these teeth can also lead to better outcomes for patients.

Bone grafting is routinely performed in periodontology and oral surgery to fill bone voids. While autogenous bone is considered the gold standard because of its regenerative properties, allografts and xenografts have more commonly been utilized owing to their availability as well as their differential regenerative/biomechanical properties. In particular, xenografts are sintered at high temperatures, which allows for their slower degradation and resorption rates and/or nonresorbable features. As a result, clinicians have combined xenografts with other classes of bone grafts (most notably allografts and autografts in various ratios) for procedures requiring better long-term stability, such as contour grafting, sinus elevation procedures, and vertical bone augmentations. This review addresses the regenerative properties of each class of bone grafts and then highlights the importance of understanding each of their biomechanical and regenerative properties for clinical applications, including extraction site management, contour augmentation, sinus grafting, and horizontal and vertical augmentation procedures. Thereafter, an introduction toward the novel production of nonresorbable bone allografts (NRBAs) via high-temperature sintering is presented. These NRBAs not only pose the advantage of being more biocompatible than xenografts owing to their origin (human vs. animal bone) but also display nonresorbable properties similar to those of xenografts. Thus, while packaging allografts with xenografts in premixtures specific to various clinical indications has never been permitted owing to cross-species contamination and FDA/CE requirements, the discovery and production of NRBAs allows premixing with standard allografts in various ratios without regulatory restrictions. Therefore, premixtures of allografts with NRBAs can be produced in various ratios for specific indications (e.g., a 1:1 ratio similar to an allograft/xenograft mixture for sinus grafting) without the need for purchasing separate classes of bone grafts. This optimized form of bone grafting could theoretically provide clinicians more precise ratios without the need to purchase separate bone grafts. This review highlights the future potential for simplified and optimized bone grafting in periodontology and implant dentistry.

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

The aim of this case report was to demonstrate the long-term effects of a multidisciplinary approach involving periodontal reconstructive surgery and strategic implant placement before orthodontic (SIMBO) treatment in a patient with severe periodontitis (e.g., stage IV/grade C).

The patient presented with severe periodontitis and pathologic tooth migration (PTM) without stable occlusion or occlusal support. After performing cause-related therapy, periodontal regenerative surgery, pre-orthodontic posterior implant placement, and orthodontic treatment involving anterior implant placement with papilla reconstruction, the patient achieved full-mouth rehabilitation and improvement of dental and smile esthetics. The clinical and radiographic results obtained were maintained over a 10-year period.

Within the limits of this as a single case, multidisciplinary treatment involving the SIMBO approach appeared to allow long-term improvement of periodontal condition, stability of the dental arches and occlusion, and esthetics in a patient with severe periodontitis, PTM and posterior bite collapse. Future studies with more subjects are needed to evaluate and validate this approach.

When addressing periodontal disease, SIMBO approach-based multidisciplinary treatment appears safe and effective as a clinical protocol for establishing esthetic and functional rehabilitation in generalized stage IV/grade C periodontitis.

This study aimed to evaluate the impact of enamel matrix derivative (EMD) application following subgingival instrumentation of residual pockets in periodontitis patients on inflammatory host response, microbiological composition, and clinical outcome.

In this double-blinded randomized controlled trial, a total of 22 patients with generalized periodontitis stage III or IV presenting with ≥ 6 mm probing pocket depth (PPD) at re-evaluation after initial periodontal therapy were included. Participants were randomly allocated at a 1:1 ratio to subgingival instrumentation with (EMD +) or without (EMD-) non-surgical EMD application into the pocket. PPD, clinical attachment level (CAL), bleeding on probing (BoP), plaque index (PI), as well as a panel of pro-inflammatory cytokines and periodontal pathogen count in the gingival crevicular fluid (GCF) of the respective sites were evaluated at baseline (T0) and six months afterwards (T1).

Both treatment groups showed a significant PPD reduction (EMD + 1.33 ± 1.15 mm, p < 0.001; EMD- 1.32 ± 1.01 mm, p < 0.001) as well as CAL gain (EMD + 1.13 ± 1.58 mm, p < 0.001; EMD- 0.47 ± 1.06 mm, p = 0.005) from T0 to T1. While no intergroup differences for PPD reduction were observed, CAL gain was higher in EMD + sites compared to EMD- (p = 0.009). No essential effects on cytokine expression as well as bacterial count were detected.

Application of EMD as an adjunct to subgingival instrumentation of residual pockets yielded benefits regarding CAL gain; however, effects on PPD reduction, inflammatory cytokines, and bacterial count were negligible.

ClinicalTrials.gov (NCT04449393), registration date 26/06/2020.

Based on the obtained results, additional non-surgical EMD application compared to subgingival instrumentation alone showed no clinically relevant effects on treatment outcome and underlying biological mechanisms.

Regeneration of periodontal tissues that have been destroyed by inflammatory periodontitis involves the initiation of tissue engineering and wound healing of multiple tissues involved in the function of the teeth, including the periodontal ligament, cementum, and alveolar bone. Such regeneration is termed guided tissue regeneration and the unique challenges to reconstruct these tissues involve a complex interplay of cells, signaling molecules, and scaffolds. While traditional guided tissue regeneration treatments have involved cell occlusive membranes, bone replacement graft scaffolds, and endogenous multipotent mesenchymal stem cells, the use of adjunctive materials to enhance healing outcomes has been studied and many such adjunctive factors are in common current clinical use. This report will focus on the current and emerging adjunctive growth factors and signaling molecules that can be used to optimize periodontal regeneration in periodontal intrabony defects, their mechanisms of action, the challenges associated with periodontal regeneration, and future avenues for research.

Diabetes mellitus (DM) is associated with periodontal disease. Clinically, periodontal treatment is less effective for patients with DM. Oxidative stress is one of the mechanisms that link DM to periodontitis. The production of reactive oxygen species (ROS) is increased in the periodontal tissues of patients with DM and is involved in the development of insulin resistance in periodontal tissues. Insulin resistance decreases Akt activation and inhibits cell proliferation and angiogenesis. This results in the deterioration of wound healing and tissue repair in periodontal tissues. Antioxidants and insulin resistance ameliorants may inhibit ROS production and improve wound healing, which is worsened by DM. This manuscript provides a comprehensive review of the most recent basic and clinical evidence regarding the generation of ROS in periodontal tissues resulting from microbial challenge and DM. This study also delves into the impact of oxidative stress on wound healing in the context of periodontal and dental implant therapies. Furthermore, it discusses the potential benefits of administering antioxidants and anti-insulin resistance medications, which have been shown to counteract ROS production and inflammation. This approach may potentially enhance wound healing, especially in cases exacerbated by hyperglycemic conditions.

Epithelial cells in periodontitis patients increasingly express chemokines, suggesting their active involvement in the inflammatory process. Enamel matrix derivative (EMD) is an extract of porcine fetal tooth germs clinically applied to support the regrowth of periodontal tissues. Periodontal regeneration might benefit from the potential anti-inflammatory activity of EMD for epithelial cells. Our aim was, therefore, to set up a bioassay where chemokine expression is initiated in the HSC2 oral squamous carcinoma cell line and then test EMD for its capacity to lower the inflammatory response. To establish the bioassay, HSC2 cells being exposed to TNFα and LPS from E. coli (Escherichia coli) or P. gingivalis (Porphyromonas gingivalis) were subjected to RNAseq. Here, TNFα but not LPS caused a robust increase of chemokines, including CXCL1, CXCL2, CXCL8, CCL5, and CCL20 in HSC2 cells. Polymerase chain reaction confirmed the increased expression of the respective chemokines in cells exposed to TNFα and IL-1β. Under these conditions, EMD reduced the expression of all chemokines at the transcriptional level and CXCL8 by immunoassay. The TGF-β receptor type I kinase-inhibitor SB431542 reversed the anti-inflammatory activity. Moreover, EMD-activated TGF-β-canonical signaling was visualized by phosphorylation of smad3 and nuclear translocation of smad2/3 in HSC2 cells and blocked by SB431542. This observation was confirmed with primary oral epithelial cells where EMD significantly lowered the SB431542-dependent expression of CXCL8. In summary, our findings suggest that TGF-β signaling mediates the effects of EMD to lower the forced expression of chemokines in oral epithelial cells.

To histologically evaluate the effects of a novel human recombinant amelogenin (rAmelX) on periodontal wound healing / regeneration in recession-type defects.

A total of 17 gingival recession-type defects were surgically created in the maxilla of three minipigs. The defects were randomly treated with a coronally advanced flap (CAF) and either rAmelX (test), or a CAF and placebo (control). At three months following reconstructive surgery, the animals were euthanized, and the healing outcomes histologically evaluated.

The test group yielded statistically significantly (p = 0.047) greater formation of cementum with inserting collagen fibers compared with the control group (i.e., 4.38 mm ± 0.36 mm vs. 3.48 mm ± 1.13 mm). Bone formation measured 2.15 mm ± 0.8 mm in the test group and 2.24 mm ± 1.23 mm in the control group, respectively, without a statistically significant difference (p = 0.94).

The present data have provided for the first-time evidence for the potential of rAmelX to promote regeneration of periodontal ligament and root cementum in recession-type defects, thus warranting further preclinical and clinical testing.

The present results set the basis for the potential clinical application of rAmelX in reconstructive periodontal surgery.

Regenerative medicine has gained much attention and has been a hot topic in all medical fields since its inception, and dentistry is no exception. However, innovations and developments in basic research are sometimes disconnected from daily clinical practice. This existing gap between basic research and clinical practice can only be addressed with improved communication between clinicians, academicians, industry, and researchers to facilitate the advance of evidence-based therapies and procedures and to direct research to areas of clinical need. In this perspective, six participants with strong clinical and research interests debated five previously conceived questions. These questions covered current methods and procedures for soft and hard tissue regeneration in the oral cavity with predictable outcomes, limitations of their respective protocols, and needs for future development of regenerative materials and technologies.

The aims of this clinical trial were to evaluate the radiographic dimensional changes in alveolar ridge and patient-reported outcomes following tooth extraction and alveolar ridge preservation (ARP) using either deproteinized bovine bone mineral (DBBM) with EMD or DBBM alone.

Participants requiring at least one posterior tooth extraction and ARP were randomly allocated into two treatment groups: ARP using either DBBM with EMD or DBBM alone. Cone-beam computed tomography (CBCT) images were recorded immediately prior to extraction and at 6 months. Changes in alveolar ridge height (ARH) and alveolar ridge width (ARW) at 1, 3, and 5 mm were recorded.

A total of 18 participants with 25 preserved sites were evaluated. ARH and ARW changed significantly from baseline to 6 months for both treatment groups but the difference between the groups was not statistically significant over the 6-month follow-up period (ARH: DBBM/EMD 1.26 ± 1.53 mm vs. DBBM 2.26 ± 1.60 mm; ARW-1 DBBM/EMD 1.98 ± 1.80 mm vs. DBBM 2.34 ± 1.89 mm). A significant difference, favoring DBBM with EMD group, was observed in percentage of sites that had less than 1 mm loss in ARH (54.5% sites in DBBM/EMD group vs. 14.3% sites in DBBM alone group). The participants' perception of bruising, bleeding, and pain in the first two postoperative days was significantly in favor of DBBM alone group.

There were no significant differences in radiographic mean measurements of ARH and ARW following ARB with DBBM and EMD or DBBM alone.

If left untreated, periodontitis is a chronic, irreversible disease that can contribute to tooth loss. The primary objective of periodontal treatment is to arrest the progression of the disease and restore the supporting structures of the tooth. Scaling and root planing (SRP) is a common non-surgical periodontal therapy (NSPT) used to reduce inflammation, pocket depth, and clinical attachment loss. However, NSPT has limitations, notably in difficult-to-access deep pockets and molar furcations. Deep pockets (greater than 4 mm) frequently retain calculus following NSPT. To attain direct access, surgical periodontal therapy (SPT) is recommended, particularly for pockets deeper than 5 mm. Enamel matrix derivative (EMD) has emerged in recent years as a tool for periodontal regeneration when used in conjunction with NSP for infrabony defects. EMD may also have advantageous effects when combined with NSPT. The purpose of this review is to provide a thorough understanding of the effects of EMD as an adjunct to NSPT. The databases Scopus, PubMed/MEDLINE, Google Scholar, Cochrane, and Embase were systematically searched to identify relevant studies on the benefits of EMD and its use as an adjunct to NSPT. Incorporating EMD into NSPT reduces chair time, and 60% of studies demonstrated considerable benefits compared to SRP alone, according to the findings. On the basis of research, it can be concluded that EMD can be used as an adjunct to NSPT, thereby reducing the amount of time spent in the operating chair. In some cases, it can, therefore, be regarded as an alternative to surgical treatment.

To study the effects of advanced platelet-rich fibrin (A-PRF+) and enamel matrix derivative (EMD) compared to open flap debridement (OFD) alone in molar furcation sites grade II on clinical and wound healing parameters.

A randomized controlled trial was designed. Eligible patients were randomly allocated to one of three treatment groups: A-PRF+, EMD or OFD. The patients and clinical examiners were blinded for the treatment received. A minimally invasive microsurgical approach was performed for the three modalities. Clinical measurements were scored at baseline and 6 months post-operatively. The clinical healing of each furcation was scored via the Early Wound Healing Index on day 3, 1 week, 2 weeks and 6 weeks.

17 patients (A-PRF+ n = 6, EMD n = 5, OFD n = 6) completed the 6 months of follow-up. The further completion of the trial had to be cancelled due to the COVID-19 pandemic. In three patients in the A-PRF+ group, the grade II of the treated furcation regressed to grade I; the corresponding number in the EMD and OFD groups was zero and one respectively. Further, 3, 1 and 4 patients in the PRF, EMD and OFD groups respectively, showed a gain of bone level ≥1 mm. The defects in the A-PRF+ group showed delayed early healing compared to the EMD and OFD groups.

The case series (RCT design) suggests a slight advantage for A-PRF+ over EMD and OFD, regarding the regressing of a furcation II to grade I; however this treatment showed delayed early wound healing compared to EMD or OFD.

https://www.isrctn.com/, identifier ISRCTN13520922.

The aim of this in vivo study was to investigate the effect of occlusal hypofunction on alveolar bone healing in the absence or presence of an enamel matrix derivative (EMD). A standardized fenestration defect over the root of the mandibular first molar in 15 Wistar rats was created. Occlusal hypofunction was induced by extraction of the antagonist. Regenerative therapy was performed by applying EMD to the fenestration defect. The following three groups were established: (a) normal occlusion without EMD treatment, (b) occlusal hypofunction without EMD treatment, and (c) occlusal hypofunction with EMD treatment. After four weeks, all animals were sacrificed, and histological (hematoxylin and eosin, tartrate-resistant acid phosphatase) as well as immunohistochemical analyses (periostin, osteopontin, osteocalcin) were performed. The occlusal hypofunction group showed delayed bone regeneration compared to the group with normal occlusion. The application of EMD could partially, but not completely, compensate for the inhibitory effects of occlusal hypofunction on bone healing, as evidenced by hematoxylin and eosin and immunohistochemistry for the aforementioned molecules. Our results suggest that normal occlusal loading, but not occlusal hypofunction, is beneficial to alveolar bone healing. Adequate occlusal loading appears to be as advantageous for alveolar bone healing as the regenerative potential of EMD.

In the recent years, platelet-rich fibrin (PRF) has gained importance in regenerative medicine due to its attributed tissue-inducing properties. However, it is still unclear whether there are benefits from using PRF with open flap debridement (OFD) for the treatment of intrabony defects compared to OFD alone. For this reason, in this study, we performed an overview of systematic reviews with Friendly Summaries of the Body of Evidence using Epistemonikos methodology on the use of PRF with OFD compared to OFD alone for the treatment of intrabony defects. We performed a systematic search in the Epistemonikos database. We extracted data from the included systematic reviews and reanalyzed the data of primary studies and generated a summary of the findings table. We used Review Manager (RevMan) v5.3 software and GRADEpro software for data analysis and data presentation. Eighteen systematic reviews were included after full-text screening, which had 16 clinical trials. Results were reported by the mean difference (MD); the following outcomes were analyzed: change in intrabony defect depth (MD: 1.37 mm more), change in radiographic bone defect filling (MD: 37.26% more), change in probing depth (MD: 1.22 mm more), change in clinical attachment level (MD: 1.32 mm more), and change in gingival margin level (MD: 0.31 more). We concluded that applying PRF with OFD to treat an intrabony defect has some clinical advantages compared to OFD alone.