A photoresponsive recombinant human amelogenin-loaded hyaluronic acid hydrogel promotes bone regeneration.

OBJECTIVES: In order to evaluate the effect of methacrylated hyaluronic acid (HAMA) hydrogels containing the recombinant human amelogenin (rhAm) in vitro and in vivo. BACKGROUND: The ultimate goal in treating periodontal disease is to control inflammation and achieve regeneration of periodontal tissues. In recent years, methacrylated hyaluronic acid (HAMA) containing recombinant human amyloid protein (rhAm) has been widely used as a new type of biomaterial in tissue engineering and regenerative medicine. However, there is a lack of comprehensive research on the periodontal regeneration effects of this hydrogel. This experiment aims to explore the application of photoresponsive recombinant human amelogenin-loaded hyaluronic acid hydrogel for periodontal tissue regeneration and provide valuable insights into its potential use in this field. MATERIALS AND METHODS: The effects of rhAm-HAMA hydrogel on the proliferation of human periodontal ligament cells (hPDLCs) were assessed using the CCK-8 kit. The osteogenic differentiation of hPDLCs was evaluated through ALP staining and real-time PCR. Calvarial parietal defects were created in 4-week-old Sprague Dawley rats and implanted with deproteinized bovine bone matrix in different treatment groups. The animals were euthanized after 4 and 8 weeks of healing. The bone volume of the defect was observed by micro-CT and histological analysis. RESULTS: Stimulating hPDLCs with rhAm-HAMA hydrogel did not significantly affect their proliferation (p > .05). ALP staining and real-time PCR results demonstrated that the rhAm-HAMA group exhibited a significant upregulation of osteoclastic gene expression (p < .05). Micro-CT results revealed a significant increase in mineralized tissue volume fraction (MTV/TV%), trabecular bone number (Tb.N), and mineralized tissue density (MTD) of the bone defect area in the rhAm-HAMA group compared to the other groups (p < .05). The results of hematoxylin and eosin staining and Masson staining at 8 weeks post-surgery further supported the results of the micro-CT. CONCLUSIONS: The results of this study indicate that rhAm-HAMA hydrogel could effectively promote the osteogenic differentiation of hPDLCs and stabilize bone substitutes in the defects that enhance the bone regeneration in vivo.

Preclinical evaluation of a new synthetic carbonate apatite bone substitute on periodontal regeneration in intrabony defects.

OBJECTIVE: To evaluate the potential of a novel synthetic carbonate apatite bone substitute (CO3 Ap-BS) on periodontal regeneration. BACKGROUND: The use of various synthetic bone substitutes as a monotherapy for periodontal regeneration mainly results in a reparative healing pattern. Since xenografts or allografts are not always accepted by patients for various reasons, a synthetic alternative would be desirable. METHODS: Acute-type 3-wall intrabony defects were surgically created in 4 female beagle dogs. Defects were randomly allocated and filled with CO3 Ap-BS (test) and deproteinized bovine bone mineral (DBBM) or left empty (control). After 8 weeks, the retrieved specimens were scanned by micro-CT, and the percentages of new bone, bone substitute, and soft tissues were evaluated. Thereafter, the tissues were histologically and histometrically analyzed. RESULTS: Healing was uneventful in all animals, and defects were present without any signs of adverse events. Formation of periodontal ligament and cementum occurred to varying extent in all groups without statistically significant differences between the groups. Residues of both bone substitutes were still present and showed integration into new bone. Histometry and micro-CT revealed that the total mineralized area or volume was higher with the use of CO3 Ap-BS compared to control (66.06 ± 9.34%, 36.11 ± 6.40%; p = .014, or 69.74 ± 2.95%, 42.68 ± 8.68%; p = .014). The percentage of bone substitute surface covered by new bone was higher for CO3 Ap-BS (47.22 ± 3.96%) than for DBBM (16.69 ± 5.66, p = .114). CONCLUSIONS: CO3 Ap-BS and DBBM demonstrated similar effects on periodontal regeneration. However, away from the root surface, more new bone, total mineralized area/volume, and higher osteoconductivity were observed for the CO3 Ap-BS group compared to the DBBM group. These findings point to the potential of CO3 Ap-BS for periodontal and bone regeneration.

Predictive factors of periodontal regeneration outcomes using rhFGF-2: A case-control study.

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.

Octacalcium phosphate collagen composite for periodontal regeneration in a canine one-wall intrabony defect.

OBJECTIVE: This study aimed to evaluate the regenerative capacities of octacalcium phosphate collagen composite (OCP/Col) in one-wall intrabony defects in dogs. The background data discuss the present state of the field: No study has assessed the efficacy of OCP/Col for periodontal regeneration therapy despite the fact that OCP/Col has proved to be efficient for bone regeneration. METHODS: In six beagle dogs, the mandibular left third premolars were extracted 12 weeks before the experimental surgery. Standardized bone defects (5 mm in height and 4 mm in width) were simulated on the distal surface of the second premolars and mesially on the fourth premolars. The defect was filled with either OCP/Col (experimental group) or left empty (control group). Histological and histomorphometric characteristics were compared 8 weeks after surgery. RESULTS: No infectious or ankylotic complications were detected at any of the tested sites. The experimental group exhibited a significantly greater volume, height, and area of newly formed bone than the control group. The former also showed a greater height of the newly formed cementum than the latter, although the results were not statistically significant. The newly formed periodontal ligaments were inserted into newly formed bone and cementum in the experimental group. CONCLUSION: OCP/Col demonstrated high efficacy for bone and periodontal tissue regeneration that can be successfully applied for one-wall intrabony defects.

Enhanced immunomodulation and periodontal regeneration efficacy of subgingivally delivered progranulin-loaded hydrogel as an adjunct to non-surgical treatment for Class II furcation involvement in dogs.

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.

The flapless approach with and without enamel matrix derivatives for the treatment of intrabony defects: A randomized controlled clinical trial.

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.

Clinical benefits of autologous platelet concentrate in periodontal intrabony defects: A network meta-analysis of randomized controlled trials.

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.

Inflammatory and bone remodelling related biomarkers following periodontal transplantation of the tissue engineered biocomplex.

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.

Impact of Inflammatory Markers and Senescence-Associated Secretory Phenotype in the Gingival Crevicular Fluid on the Outcomes of Periodontal Regeneration.

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)-1ß, 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-1ß 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.

Insights and Advancements in Periodontal Tissue Engineering and Bone Regeneration.

The regeneration of periodontal bone defects continues to be an essential therapeutic concern in dental biomaterials. Numerous biomaterials have been utilized in this sector so far. However, the immune response and vascularity in defect regions may be disregarded when evaluating the effectiveness of biomaterials for bone repair. Among several regenerative treatments, the most recent technique of in situ tissue engineering stands out for its ability to replicate endogenous restorative processes by combining scaffold with particular growth factors. Regenerative medicine solutions that combine biomaterials/scaffolds, cells, and bioactive substances have attracted significant interest, particularly for bone repair and regeneration. Dental stem cells (DSCs) share the same progenitor and immunomodulatory properties as other types of MSCs, and because they are easily isolable, they are regarded as desirable therapeutic agents in regenerative dentistry. Recent research has demonstrated that DSCs sown on newly designed synthetic bio-material scaffolds preserve their proliferative capacity while exhibiting increased differentiation and immuno-suppressive capabilities. As researchers discovered how short peptide sequences modify the adhesion and proliferative capacities of scaffolds by activating or inhibiting conventional osteogenic pathways, the scaffolds became more effective at priming MSCs. In this review, the many components of tissue engineering applied to bone engineering will be examined, and the impact of biomaterials on periodontal regeneration and bone cellular biology/molecular genetics will be addressed and updated.

Healing of Periodontal Suprabony Defects following Treatment with Open Flap Debridement with or without Hyaluronic Acid (HA) Application.

Background and Objectives: This randomized, double-arm, multicentric clinical trial aims to compare the clinical outcomes following the treatment of suprabony periodontal defects using open flap debridement (OFD) with or without the application of hyaluronic acid (HA). Materials and Methods: Sixty systemically healthy patients with at least two teeth presenting suprabony periodontal defects were randomly assigned with a 1:1 allocation ratio using computer-generated tables into a test (OFD + HA) or control group (OFD). The main outcome variable was clinical attachment level (CAL). The secondary outcome variables were changes in mean probing pocket depth (PPD), gingival recession (GR), full-mouth plaque score (FMPS), and full-mouth bleeding score (FMBS). All clinical measurements were carried out at baseline and 12 months. Results: Sixty patients, thirty in each group, were available for statistical analysis. The mean CAL gain was statistically significantly different (p < 0.001) in the test group compared with the control group (3.06 ± 1.13 mm vs. 1.44 ± 1.07 mm). PPD reduction of test group measurements (3.28 ± 1.14 mm) versus the control group measurements (2.61 ± 1.22 mm) were statistically significant (p = 0.032). GR changes were statistically significant only in the test group 0.74 ± 1.03 mm (p < 0.001). FMBS and FMPS revealed a statistically significant improvement mostly in the test group. Conclusions: Suprabony periodontal defects could benefit from the additional application of HA in conjunction with OFD in terms of improvement of the clinical parameters compared with OFD alone.

Evaluation of Regenerative Efficacy of Amnion and Chorion Membrane in Treatment of Mandibular Molar Furcation Defects: A Clinico-radiographic Study.

AIM: Amnion and chorion membranes possess unique inherited biological properties that enhance wound healing and may accelerate periodontal regeneration. The present study aims to evaluate and compare the efficacy of amnion and chorion membranes in the treatment of furcation defects. MATERIALS AND METHODS: A total of 20 patients were selected and were randomly allocated to group I and group II with 10 subjects in each group. Amnion and chorion membranes are placental-derived membranes that accelerate regeneration by having natural growth factors with their antimicrobial and inflammation reduction properties. Group I was treated using bone grafting with decalcified freeze-dried bone allograft (DFDBA) and placement of amnion as a membrane for guided tissue regeneration (GTR) whereas group II was treated using bone grafting with DFDBA and placement of chorion as a membrane for GTR. The patients were followed for clinical and radiographic parameters and were evaluated between 3 and 6 months after surgery. RESULT: In intragroup comparison, a significant difference was evident in both the groups for all the clinical and radiographic parameters within the groups. (p = 0.01) This means both amnion and chorion membranes showed statistically significant regenerative efficacy. In intergroup comparison, the results show that all the clinical parameters and radiographic parameters show no significant difference between the groups. CONCLUSION: The amnion and chorion membranes had similar regenerative efficacy in combination with DFDBA in patients with buccal degree II furcation defects in mandibular molars. CLINICAL SIGNIFICANCE: The amnion and chorion membranes have shown significant improvement in clinical and radiographic parameters when used for the treatment of buccal degree II furcation defects in mandibular molars. How to cite this article: Mallapragda S, Gupta R, Gupta S, et al. Evaluation of Regenerative Efficacy of Amnion and Chorion Membrane in Treatment of Mandibular Molar Furcation Defects: A Clinico-radiographic Study. J Contemp Dent Pract 2024;25(2):160-167.

Let-7a promotes periodontal bone regeneration of bone marrow mesenchymal stem cell aggregates via the Fas/FasL-autophagy pathway.

Periodontal bone regeneration using bone marrow mesenchymal stem cell (BMMSC) transplantation is a promising method; however, the method for osteogenic differentiation of BMMSCs needs to be improved. In this research, we sought to identify the roles of let-7a in the osteogenesis of BMMSCs and to provide a potential method for periodontal bone regeneration. Our previous study revealed that Fas/FasL is a target of let-7a. In this study, we demonstrated that let-7a overexpression significantly enhanced BMMSC-CAs osteogenesis both in vitro and in vivo. Mechanistically, upregulation of Fas/FasL using the rfas/rfaslg plasmid obstructed the osteogenesis of BMMSCs by inhibiting autophagy. Furthermore, we confirmed that overexpression of let-7a activated autophagy and alleviated the inhibited osteogenesis by the autophagy inhibitor 3-MA and the rfas/rfaslg plasmid of BMMSCs. In general, our findings showed that let-7a promoted the osteogenesis of BMMSCs through the Fas/FasL-autophagy pathway, suggesting that the application of let-7a in BMMSC-CAs based periodontal bone regeneration could be a promising strategy.

The role of non-steroidal anti-inflammatory drugs as adjuncts to periodontal treatment and in periodontal regeneration.

Periodontitis is the sixth most prevalent chronic disease globally and places significant burdens on societies and economies worldwide. Behavioral modification, risk factor control, coupled with cause-related therapy have been the "gold standard" treatment for managing periodontitis. Given that host inflammatory and immunological responses play critical roles in the pathogenesis of periodontitis and impact treatment responses, several adjunctive strategies aimed at modulating host responses and improving the results of periodontal therapy and maintenance have been proposed. Of the many pharmacological host modulators, we focused on non-steroidal anti-inflammatory drugs (NSAIDs), due to their long history and extensive use in relieving inflammation and pain and reducing platelet aggregation. NSAIDs have been routinely indicated for treating rheumatic fever and osteoarthritis and utilized for the prevention of cardiovascular events. Although several efforts have been made to incorporate NSAIDs into the treatment of periodontitis, their effects on periodontal health remain poorly characterized, and concerns over the risk-benefit ratio were also raised. Moreover, there is emerging evidence highlighting the potential of NSAIDs, especially aspirin, for use in periodontal regeneration. This review summarizes and discusses the use of NSAIDs in various aspects of periodontal therapy and regeneration, demonstrating that the benefits of NSAIDs as adjuncts to conventional periodontal therapy remain controversial. More recent evidence suggests a promising role for NSAIDs in periodontal tissue engineering and regeneration.

Complications and treatment errors related to regenerative periodontal surgery.

Regenerative periodontal surgical procedures are an important component in the treatment of advanced periodontitis. They aim to improve the long-term prognosis of teeth that are periodontally compromised by the presence of intrabony and/or furcation defects, resulting biologically in formation of root cementum, periodontal ligament, and alveolar bone and evidenced clinically by reduction of deep pockets to maintainable probing depths and/or improvements of vertical and horizontal furcation depth. Over the last 25 years, substantial clinical evidence has been accumulated to support the value of regenerative procedures in periodontally compromised dentitions. However, treatment success requires close attention to certain factors on the level of the patient, the tooth/defect, and the operator. Ignoring these factors in case selection, treatment planning, and treatment execution will increase the risk of complications that may jeopardize clinical success and may even be considered as treatment errors. Based on the currently available evidence from clinical practice guidelines, treatment algorithms, and on expert opinion, the present article provides an overview on the main factors, which influence the outcomes of regenerative periodontal surgery and gives recommendations on how to prevent complications and treatment errors.

Ion incorporation into bone grafting materials.

The use of biomaterials in regenerative medicine has expanded to treat various disorders caused by trauma or disease in orthopedics and dentistry. However, the treatment of large and complex bone defects presents a challenge, leading to a pressing need for optimized biomaterials for bone repair. Recent advances in chemical sciences have enabled the incorporation of therapeutic ions into bone grafts to enhance their performance. These ions, such as strontium (for bone regeneration/osteoporosis), copper (for angiogenesis), boron (for bone growth), iron (for chemotaxis), cobalt (for B12 synthesis), lithium (for osteogenesis/cementogenesis), silver (for antibacterial resistance), and magnesium (for bone and cartilage regeneration), among others (e.g., zinc, sodium, and silica), have been studied extensively. This review aims to provide a comprehensive overview of current knowledge and recent developments in ion incorporation into biomaterials for bone and periodontal tissue repair. It also discusses recently developed biomaterials from a basic design and clinical application perspective. Additionally, the review highlights the importance of precise ion introduction into biomaterials to address existing limitations and challenges in combination therapies. Future prospects and opportunities for the development and optimization of biomaterials for bone tissue engineering are emphasized.

Twenty-five years of recombinant human growth factors rhPDGF-BB and rhBMP-2 in oral hard and soft tissue regeneration.

Contemporary oral tissue engineering strategies involve recombinant human growth factor approaches to stimulate diverse cellular processes including cell differentiation, migration, recruitment, and proliferation at grafted areas. Recombinant human growth factor applications in oral hard and soft tissue regeneration have been progressively researched over the last 25 years. Growth factor-mediated surgical approaches aim to accelerate healing, tissue reconstruction, and patient recovery. Thus, regenerative approaches involving growth factors such as recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human bone morphogenetic proteins (rhBMPs) have shown certain advantages over invasive traditional surgical approaches in severe hard and soft tissue defects. Several clinical studies assessed the outcomes of rhBMP-2 in diverse clinical applications for implant site development and bone augmentation. Current evidence regarding the clinical benefits of rhBMP-2 compared to conventional therapies is inconclusive. Nevertheless, it seems that rhBMP-2 can promote faster wound healing processes and enhance de novo bone formation, which may be particularly favorable in patients with compromised bone healing capacity or limited donor sites. rhPDGF-BB has been extensively applied for periodontal regenerative procedures and for the treatment of gingival recessions, showing consistent and positive outcomes. Nevertheless, current evidence regarding its benefits at implant and edentulous sites is limited. The present review explores and depicts the current applications, outcomes, and evidence-based clinical recommendations of rhPDGF-BB and rhBMPs for oral tissue regeneration.

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

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

The role of rhFGF-2 in periodontal defect bone fill: A systematic review of the literature.

BACKGROUND: Growth factors have been used with success in periodontal regeneration, especially in intrabony defects. Among those, the recombined form of fibroblast growth factor-2 (rhFGF-2) has been also examined. OBJECTIVE: To address the outcomes of periodontal regeneration using rhFGF-2 alone or in combination with bone substitutes primarily in terms of Radiographic Bone Fill (RBF%) and secondary Probing Pocket Depth (PPD), and Probing Attachment Levels (PAL). MATERIAL AND METHODS: A search in MEDLINE and EMBASE using the Ovid interface was conducted from 2000 up to and including the 12th of November 2022. Starting from the initially identified 1289 articles, 34 studies were selected for further analysis. Following the full-text screening, 7 of the 34 studies met the inclusion criteria and thus were included in the systematic review after assessing their quality according to the Newcastle-Ottawa scale (NOS). Clinical and radiographic results (bone gain, pocket depth, and clinical attachment level) after the application of FGF-2 alone or in combination with different carriers were studied in patients with intrabony defects of at least one wall and pocket depth greater than 4 mm. RESULTS: Primary outcomes: RBF% was higher in studies using a combination of rhFGF-2 and bone substitutes (74.6 ± 20.0%) compared to others using the specific growth factor alone or negative controls (22.7 ± 20.7%). In terms of secondary outcomes, the analysis failed to show an additional benefit from the use of the rhFGF-2 alone or in combination with bone substitutes. CONCLUSION: rhFGF-2 can improve RBF% in the treatment of periodontal defects, especially when it is used in combination with a bone substitute.

Influence of locally delivered doxycycline on the clinical and molecular inflammatory status of intrabony defects prior to periodontal regeneration: A double-blind randomized controlled trial.

OBJECTIVES: To test the effect of locally delivered doxycycline (DOX) administered 2 weeks prior to minimally invasive periodontal regeneration in terms of presurgical inflammatory status and cytokine expression profile in the gingival crevicular fluid (GCF). Secondary aim was to assess the early wound healing index (EHI) at 2 weeks after surgery. BACKGROUND: It is hypothesized that healing after periodontal regeneration is dependent on preoperative soft tissue condition, and that local antibiotics may improve the site-specific inflammatory status at short time. METHODS: Sites associated with periodontal intrabony defects requiring regenerative surgery and showing bleeding on probing (BoP) were included. At T0, experimental sites were randomly treated with subgingival instrumentation with or without topic DOX application. After 2 weeks (T1), defects were approached by means of minimally invasive surgical technique. GCF was sampled at both T0 and T1 for inflammatory biomarker analysis. Two weeks after surgery, the EHI was evaluated (T2). RESULTS: Forty-four patients were included. At T1, the number of BoP+ sites was statistically significantly less in the test group (27.3% vs. 72.7%; p < .01). The total amount of interleukin (IL)-1ß (p < .001), matrix-metalloproteinases (MMP)-8 (p < .001), and MMP-9 (p = .010) in the GCF significantly decreased in the test group at T1, with relevant differences compared to controls. At T2, the EHI had an average value of 1.45 ± 0.86 in the test group while in the control, it was 2.31 ± 1.43 (p = .027). A statistically significantly positive correlation was observed between the amount of IL-1ß and MMP-9 and EHI scores. CONCLUSIONS: Within the limitations of this study, sites treated with DOX showed improved clinical and molecular inflammatory parameters before surgery, as well as soft tissue healing 2 weeks after surgery.