Understanding exosomes: Part 2-Emerging leaders in regenerative medicine.

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of diseases/conditions. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be developed. Today exosomes have been applied in numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's disease, post-traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology disorders, musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID-19, hepatitis), regenerative procedures (antiaging, bone regeneration, cartilage/joint regeneration, osteoarthritis, cutaneous wounds, dental regeneration, dermatology/skin regeneration, erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord injury, vascular regeneration), and cancer therapy (breast, colorectal, gastric cancer and osteosarcomas), immune function (allergy, autoimmune disorders, immune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review is a first of its kind aimed at summarizing the extensive regenerative potential of exosomes over a broad range of diseases and disorders.

Understanding exosomes: Part 3-therapeutic + diagnostic potential in dentistry.

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of various diseases. Over 5000 publications are currently being published on this topic yearly, many of which in the dental space. This extensive review article is the first scoping review aimed at summarizing all therapeutic uses of exosomes in regenerative dentistry. A total of 944 articles were identified as using exosomes in the dental field for either their regenerative/therapeutic potential or for diagnostic purposes derived from the oral cavity. In total, 113 research articles were selected for their regenerative potential (102 in vitro, 60 in vivo, 50 studies included both). Therapeutic exosomes were most commonly derived from dental pulps, periodontal ligament cells, gingival fibroblasts, stem cells from exfoliated deciduous teeth, and the apical papilla which have all been shown to facilitate the regenerative potential of a number of tissues including bone, cementum, the periodontal ligament, nerves, aid in orthodontic tooth movement, and relieve temporomandibular joint disorders, among others. Results demonstrate that the use of exosomes led to positive outcomes in 100% of studies. In the bone field, exosomes were found to perform equally as well or better than rhBMP2 while significantly reducing inflammation. Periodontitis animal models were treated with simple gingival injections of exosomes and benefits were even observed when the exosomes were administered intravenously. Exosomes are much more stable than growth factors and were shown to be far more resistant against degradation by periodontal pathogens found routinely in a periodontitis environment. Comparative studies in the field of periodontal regeneration found better outcomes for exosomes even when compared to their native parent stem cells. In total 47 diagnostic studies revealed a role for salivary/crevicular fluid exosomes for the diagnosis of birth defects, cardiovascular disease, diabetes, gingival recession detection, gingivitis, irritable bowel syndrome, neurodegenerative disease, oral lichen planus, oral squamous cell carcinoma, oropharyngeal cancer detection, orthodontic root resorption, pancreatic cancer, periodontitis, peri-implantitis, Sjögren syndrome, and various systemic diseases. Hence, we characterize the exosomes as possessing "remarkable" potential, serving as a valuable tool for clinicians with significant advantages.

Clinical Use of a Mineral-Organic Resorbable Bone Adhesive: A First Human Case Report with a 3-Year Follow-up.

The ability for clinicians to adequately obtain primary stability in host bone is critical to the success of dental implants. Numerous conditions require dentists to perform multistage approaches to rebuild deficient bone volume prior to surgically placing implants. In many instances, implant placement cannot be achieved due to a lack of primary implant stability. Recently, a novel mineral-organic resorbable bone adhesive (MORBA) has demonstrated promising results in animal studies. MORBA is a synthetic, injectable, self-setting, load-bearing adhesive biomaterial that exhibits osteopromotive properties and bonds bone to bone and metal within 10 minutes and can fully resorb in 30 weeks. Its unique novel formulation was developed from biomimetic proteins found in marine animal creatures that possess distinct adhesive properties underwater. Excellent long-term results have shown its potential use for achieving primary stability in immediate implants. The present case report demonstrates the first use of MORBA in a human patient, utilized on a nonrestorable mandibular first molar. MORBA was utilized after placement of a mobile 5.8-mm implant to achieve stabilization. At 3 months postsurgery, both clinical and CBCT evaluations showed maintained implant stability. One year after implant placement, radiographic bone was seen on the buccal surface of the implant with continued long-term stabilization. This case report extends to 3 years whereby the use of MORBA, in an initially unstable situation, demonstrated an excellent long-term follow-up. MORBA provided immediate implant stability with resorbable characteristics, leading to successful long-term clinical outcomes up to 3 years. This innovative biomaterial offers a more efficient solution to a critical problem in implant dentistry, allowing optimal primary stability during immediate implant placement, thus reducing treatment times and costs.

Emerging factors affecting peri-implant bone metabolism.

Implant dentistry has evolved to the point that standard implant osseointegration is predictable. This is attributed in part to the advancements in material sciences that have led toward improvements in implant surface technology and characteristics. Nonetheless, there remain several cases where implant therapy fails (specifically at early time points), most commonly attributed to factors affecting bone metabolism. Among these patients, smokers are known to have impaired bone metabolism and thus be subject to higher risks of early implant failure and/or late complications related to the stability of the peri-implant bone and mucosal tissues. Notably, however, emerging data have unveiled other critical factors affecting osseointegration, namely, those related to the metabolism of bone tissues. The aim of this review is to shed light on the effects of implant-related factors, like implant surface or titanium particle release; surgical-related factors, like osseodensification or implanted biomaterials; various drugs, like selective serotonin reuptake inhibitors, proton pump inhibitors, anti-hypertensives, nonsteroidal anti-inflammatory medication, and statins, and host-related factors, like smoking, diet, and metabolic syndrome on bone metabolism, and aseptic peri-implant bone loss. Despite the infectious nature of peri-implant biological complications, these factors must be surveyed for the effective prevention and management of peri-implantitis.

Osteoinduction and osteoimmunology: Emerging concepts.

The recognition and importance of immune cells during bone regeneration, including around bone biomaterials, has led to the development of an entire field termed "osteoimmunology," which focuses on the connection and interplay between the skeletal system and immune cells. Most studies have focused on the "osteogenic" capacity of various types of bone biomaterials, and much less focus has been placed on immune cells despite being the first cell type in contact with implantable devices. Thus, the amount of literature generated to date on this topic makes it challenging to extract needed information. This review article serves as a guide highlighting advancements made in the field of osteoimmunology emphasizing the role of the osteoimmunomodulatory properties of biomaterials and their impact on osteoinduction. First, the various immune cell types involved in bone biomaterial integration are discussed, including the prominent role of osteal macrophages (OsteoMacs) during bone regeneration. Thereafter, key biomaterial properties, including topography, wettability, surface charge, and adsorption of cytokines, growth factors, ions, and other bioactive molecules, are discussed in terms of their impact on immune responses. These findings highlight and recognize the importance of the immune system and osteoimmunology, leading to a shift in the traditional models used to understand and evaluate biomaterials for bone regeneration.

Early tissue and healing responses after maxillary sinus augmentation using horizontal platelet rich fibrin bone blocks.

BACKGROUND: The effects of horizontal platelet-rich fibrin (H-PRF) bone block on the healing and immune response during sinus augmentation have not been fully investigated histologically at early time points. METHODS: Eighteenth male New Zealand white rabbits underwent bilateral sinus augmentation and were divided into two groups: deproteinized bovine bone mineral (DBBM) alone and H-PRF + DBBM (H-PRF bone block) group. Maxilla samples were collected at 3, 7 and 14 days post sinus augmentation procedures and analyzed using histological staining for the number of inflammatory cells, new blood vessels and evidence for early osteoclast bone turnover/remodeling. Furthermore, the effects of H-PRF bone blocks on the migration of osteoblasts and THP-1 macrophages were evaluated using a Transwell assay in vitro. RESULTS: A higher number of immune cells were found in the H-PRF bone block group at 3 and 7 days post-surgery when compared to the DBBM alone group,most notably in the regions close to the mucosal lining and bone plates. Furthermore, a significantly greater number of new blood vessel formations and early signs of osteoclast development were found in the H-PRF bone block group at 14 days. The in vitro transwell assay further confirmed that culture medium from H-PRF bone block markedly promote the migration of osteoblasts and THP-1 macrophages. CONCLUSIONS: The findings from this study have shown that H-PRF bone block is capable of increasing early immune cell infiltration leading to the acceleration of neovascularization and speeding the process of bone metabolism in vivo following maxillary sinus grafting with DBBM.

Optimized bone grafting.

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.

Nanocages and cell-membrane display technology as smart biomaterials.

Gold nanocages (AuNCs) have been invented and developed over two decades as biomaterial in clinical medicine with great application potential. AuNCs have a characteristic structure of porous walls with hollow interior and a compact size. This makes it possible for them to transport biomolecules or drugs with the advantages of their photothermal effects that could help further destroy germs or tumors while also regulating the release of drugs inside. Furthermore, their bioactivity and application can be broadened by using cell-membrane display technology. AuNCs have shown tremendous potential in antibacterial activity, inflammation modulation, and tissue regeneration, which is required in periodontitis and peri-implantitis treatment. Thus, this article provides an overview of AuNCs synthesis, characteristics, surface modifications, and clinical applications, aiming to serve as a reference for the design and fabrication of AuNCs-based smart materials for periodontal or peri-implant application.

Partial Extraction Therapy (Part 1): Applications in Full-Arch Dental Implant Therapy.

Partial extraction therapy (PET) is a set of surgical techniques that preserve a portion of the patient's own root structure to maintain blood supply derived from the periodontal ligament complex in order to maintain the periodontium and peri-implant tissues during restorative and implant therapy. PET includes the socket shield technique (SST), proximal shield technique (PrST), pontic shield technique (PtST), and root submergence technique (RST). In a traditional hybrid technique, total extraction and full-arch dental implant therapy often require significant bone reduction and palatal/lingual implant placement. In addition, postextraction preservation of the ridge architecture is a major challenge. This case series demonstrates the use of a combination of PET techniques with digital implant planning and guided implant surgery to achieve highly esthetic outcomes in full-arch implant therapy.

Lipids of Platelet-Rich Fibrin Reduce the Inflammatory Response in Mesenchymal Cells and Macrophages.

Platelet-rich fibrin (PRF) has a potent anti-inflammatory activity but the components mediating this effect remain unknown. Blood lipids have anti-inflammatory properties. The question arises whether this is also true for the lipid fraction of PRF. To answer this question, lipid fractions of solid and liquid PRF were tested for their potential to lower the inflammatory response of ST2 bone marrow stromal cells and primary bone marrow macrophages exposed to IL1ß and TNFα, and LPS, respectively. Cytokine production and the underlying signalling pathway were analysed by RT-PCR, immunoassays, and Western blotting. We report here that lipids from solid and liquid PRF substantially lowered cytokine-induced expression of IL6, CCL2 and CCL5 in ST2 cells. Moreover, the inflammatory response induced by Pam3CSK4, the agonist of Toll-like receptor (TLR) TLR2, was partially reduced by the lipid extracts in ST2 cells. The PRF lipids further reduced the LPS-induced expression of IL1ß, IL6 and CCL5 in macrophages at the transcriptional level. This was confirmed by showing the ability of PRF lipids to diminish IL6 at the protein level in ST2 cells and macrophages. Likewise, PRF lipid extracts reduced the phosphorylation of p38 and JNK and moderately decreased the phosphorylation of NFκB-p65 in ST2 cells. These findings suggest that the lipid fraction is at least partially responsible for the anti-inflammatory activity of PRF in vitro.

Macrophages modulate stiffness-related foreign body responses through plasma membrane deformation.

Implants are widely used in medical applications and yet macrophage-mediated foreign body reactions caused by implants severely impact their therapeutic effects. Although the extensive use of multiple surface modifications has been introduced to provide some mitigation of fibrosis, little is known about how macrophages recognize the stiffness of the implant and thus influence cell behaviors. Here, we demonstrated that macrophage stiffness sensing leads to differential inflammatory activation, resulting in different degrees of fibrosis. The potential mechanism for macrophage stiffness sensing in the early adhesion stages tends to involve cell membrane deformations on substrates with different stiffnesses. Combining theory and experiments, we show that macrophages exert traction stress on the substrate through adhesion and altered membrane curvature, leading to the uneven distribution of the curvature-sensing protein Baiap2, resulting in cytoskeleton remodeling and inflammation inhibition. This study introduces a physical model feedback mechanism for early cellular stiffness sensing based on cell membrane deformation, offering perspectives for future material design and targeted therapies.

A Zinc- and Calcium-Rich Lysosomal Nanoreactor Rescues Monocyte/Macrophage Dysfunction under Sepsis.

Sepsis is a dysregulation of the immune response to pathogens and has high morbidity and mortality worldwide. However, the unclear mapping and course of dysregulated immune cells currently hinders the development of advanced therapeutic strategies to treat sepsis. Here, evidence is provided using single-cell RNA sequencing from peripheral blood mononuclear cells in sepsis that pathogens attacking monocytes/macrophages disrupt their immune function. The results reveal an enormous decline in monocytes/macrophages in sepsis and chart the evolution of their impaired phagocytosis (Pha) capabilities. Inspired by these findings, nanoparticles, named "Alpha-MOFs," are developed that target dysfunctional monocytes/macrophages to actively (A) lift (L) Pha by the release of lysosome-sensitive ions from a mineralized metal-organic framework (MOF). Alpha-MOFs have good stability and biosafety in peripheral blood and efficiently targeted monocytes/macrophages. They also release calcium and zinc ions into monocyte/macrophage lysosomes to promote the Pha and degradation of bacteria. Taken together, these results suggest that Alpha-MOFs rescue monocytes/macrophages dysfunction and effectively improve their survival rate during sepsis.

OsteoMacs and Their Role in Early Implant Failure and Osseointegration.

Dental implant failure cannot always be explained by clinical risk factors. Recent literature suggests that immune cells are pivotal players in the integration of biomaterials and have a co-relationship within a set of osteal macrophages known as "OsteoMacs." These cells have been known to polarize quickly between a M1 pro-inflammatory and a M2 wound healing state during implant osseointegration. OsteoMacs play a critical immune surveillance role in the osseointegration of dental implant healing and bone homeostasis. This review is intended to provide an overview of the current understanding of OsteoMacs and their role in early implant failure and osseointegration.

Biological Characterization, Properties, and Clinical Use of a Novel Homeopathic Antiseptic Oral Recovery Kit: A Narrative Review.

Most available antiseptic solutions have strong antibacterial effects, but many also possess major cytotoxic effects on gingival fibroblasts, osteoblasts, osteoprogenitor cells, and/or epithelial cells. A novel VEGA Oral Care Recovery Kit (StellaLife) consisting of 16 active ingredients that are monographed in the Homeopathic Pharmacopeia of the United States (HPUS) has gained tremendous momentum as a replacement for more cytotoxic oral rinses such as chlorhexidine. While accumulating evidence has thus far supported its use, little of the gathered data have fully described the properties of the oral formulation. Therefore, the aim of the present review article was 3-fold. First, a biological characterization regarding the active ingredients found in StellaLife Recovery Kit including their biological properties was assessed in 4 predominant categories; 1) antimicrobial resistance, 2) accelerated wound healing, 3) pain management control, and 4) anti-cancer properties. The second aim of this review article was to assess both fundamental and clinical research to date comparing VEGA oral rinse (StellaLife) to the more commonly utilized CHX for differences regarding their effect on decreasing bacterial loads as well as cell viability, survival, proliferation, and expression of both regenerative cytokines and inflammatory markers. Lastly, clinical case examples are presented describing the use of StellaLife remedies in a variety of clinical situations. These include but are not limited to wisdom-tooth extraction, extraction site management, dental implants and ridge augmentation, soft-tissue grafting procedures, frenectomies, and also temporary relief of dry sockets, dry mouth, aphthous ulcers, mucositis, lichen planus, among others. In summary, findings from the present review article provide evidence from basic laboratory experiments that validate clinical studies supporting the use of the StellaLife oral rinse regarding its superior biocompatibility and wound healing properties when compared to common antiseptic solutions such as CHX.

Use of Enamel Matrix Derivative in Minimally Invasive/Flapless Approaches: A Systematic Review with Meta-Analysis.

PURPOSE: The aim of the present systematic review with meta-analysis was to investigate the clinical effectiveness of EMD (enamel matrix derivative) using a minimally invasive surgical technique (MIST) or flapless approach for the treatment of severe periodontal probing depths. MATERIALS AND METHODS: A systematic review of the literature including searches in PubMed/Medline, Cochrane Library, Google Scholar, and Grey Literature databases as well as manual searches was performed on September 1st, 2021. Studies utilising EMD in a non-surgical or minimally invasive approach were included. The eligibility criteria comprised randomised controlled trials (RCTs) comparing minimally-invasive/flapless approaches with/without EMD for the treatment of probing depths >5 mm. RESULTS: From 1525 initial articles, 7 RCTs were included and 12 case series discussed. Three studies investigated a MIST approach, whereas 3 studies utilised a flapless approach. One study compared EMD with either a MIST or a flapless approach. The RCTs included ranged from 19-49 patients with at least 6 months of follow-up. While 5 of the studies included smokers, patients smoking >20 cigarettes/day were excluded from the study. The meta-analysis revealed that EMD with MIST improved recession coverage (REC) and bone fill (BF) when compared to MIST without EMD. However, no difference in CAL or PD was observed between MIST + EMD vs MIST without EMD. No statistically significant advantage was found for employing the EMD via the flapless approach. CONCLUSIONS: Implementing EMD in MIST procedures displayed statistically significant improvement in REC and BF when compared to MIST alone. These findings suggest that MIST in combination with EMD led to improved clinical outcomes while EMD employed in nonsurgical flapless therapy yielded no clinical benefits when compared to nonsurgical therapy alone without EMD. More research is needed to substantiate these findings.

Comparison of the effects of platelet concentrates produced by high and low-speed centrifugation protocols on the healing of critical-size defects in rat calvaria: a microtomographic and histomorphometric study.

The current study evaluated the healing of critical-size defects (CSD) created in rat calvaria treated with platelet concentrates produced by high-speed (Leukocyte- and Platelet-Rich Fibrin - L-PRF) and low-speed (Advanced Platelet-Rich Fibrin - A-PRF) protocols of centrifugation. Twenty-four rats were distributed into three groups: Control, L-PRF, and A-PRF. Five mm diameter CSD were created on the animals' calvaria. The defects of the L-PRF and A-PRF groups were filled with 0.01 ml of L-PRF and A-PRF, respectively. The control group defects were filled with a blood clot only. All animals were euthanized on the 35th postoperative day. Histomorphometric and microtomographic analyses were then performed. The L-PRF and A-PRF groups had significantly higher bone volume and neoformed bone area than those of the control group and lowered bone porosity values (p < .05). No significant differences were observed between A-PRF and L-PRF groups for the analyzed parameters. Therefore, it can be concluded that i) L-PRF and A-PRF potentiated the healing of CSD in rat calvaria; ii) high and low-speed centrifugation protocols did not produce PRF matrices with different biological impacts on the amount of bone neoformation.

The effect of resting and compression time post-centrifugation on the characteristics of platelet rich fibrin (PRF) membranes.

OBJECTIVE: To evaluate the effect of resting and compression time after centrifugation on the physical properties of platelet rich fibrin (PRF) membranes, and to provide optimal guidance regarding the clinical preparation of PRF. MATERIALS AND METHODS: A total of 12 volunteers enrolled in this study divided into 2 groups equally. For each volunteer, 6 tubes of 10 mL venous whole blood was drawn. To evaluate the influence of resting time after centrifugation, PRF clots were taken out 0, 1, 3, 5, 7, and 10 min from tubes following centrifugation, and then the weight, size, maximum stress, and maximum strain of each group were measured. To evaluate the influence of compression time on the preparation of PRF membranes, the weight ratio of PRF membranes to PRF clots was calculated by compression for 10 s, 30 s, 60 s, 90 s, 120 s, and 180 s, respectively. Scanning electron microscopy was performed to observe the cross-linking of the fibers within membranes, and the maximum stress and strain of PRF membranes were tested followed by stress-strain curve analysis. RESULTS: The weight and volume of PRF clots and PRF membranes increased in size and weight reached the top at 3 min, followed by a decrease after 7-min resting. The maximum strain of the PRF membranes after 10 min decreased significantly compared to the 3-min and 5-min groups. The maximum stress was found at 3 min followed by a statistical decrease when resting time went on. Scanning electron microscopy demonstrated that the internal fibrous structure of the PRF membranes was looser when the compression time was less than 60 s when comparing the 90-s group. The maximum stress of PRF membranes was shown using a wait period of 3 min post-centrifugation followed by compression for 120 s. CONCLUSION: The findings from the present study demonstrate that the time post-centrifugation of PRF membranes showed a maximum weight, volume, and mechanical properties after resting for 3-5 min in the tube post-centrifugation followed by a compression time of 120 s. CLINICAL RELEVANCE: Although research to date has focused primarily on centrifugation protocols, this study revealed for the first time that the resting time post-centrifugation greatly affected the mechanical properties of PRF. This study demonstrated that the resting and compression time after centrifugation influences the mechanical strength of PRF membranes, which might explain differences in PRF characteristics prepared by different clinicians that may provide a standard guide for preparation of PRF membranes.

Combination of Nd:YAG and Er:YAG lasers in non-surgical periodontal therapy: a systematic review of randomized clinical studies.

Lasers are increasingly utilized in the non-surgical treatment of periodontal disease. The aim of the present systematic review with meta-analysis was to investigate the combination use of Nd:YAG and Er:YAG laser therapy in the treatment of severe periodontitis. A systematic review of the literature including searches in PubMed/Medline, Cochrane Library, Google Scholar, and Grey Literature databases, as well as manual searches, was performed until November 1, 2021. Only studies a combination of lasers during non-surgical treatment of pockets ≥ 6mm were included. The eligibility criteria for meta-analysis comprised randomized controlled trials (RCTs) comparing the use of combination laser therapy with/without adjunctive mechanical for the non-surgical management of periodontitis. From 57 initial articles, 6 full-text articles were assessed for eligibility. Two studies were excluded, one study was not a randomized clinical trial (case series), and one study was an in vitro study. Four RCTs were included in the meta-analysis. It was shown that combination of Nd:YAG and Er:YAG may be beneficial for non-surgical periodontal therapy with an additional average reduction in pocket depth and clinical attachment level reported at 1.01 and 0.77 mm respectively when compared to controls. The findings suggest that the combination of Nd:YAG and Er:YAG lasers may lead to additional clinical improvements compared to nonsurgical treatment alone. Future research is needed to substantiate these findings and optimize clinical guidelines including more specific laser protocols. Preliminary data suggest favorable outcomes following the combination of Nd:YAG and Er:YAG lasers for non-surgical periodontal therapy.

Combination of enamel matrix derivative and hyaluronic acid inhibits lipopolysaccharide-induced inflammatory response on human epithelial and bone cells.

OBJECTIVES: The aim of this study was to evaluate the in vitro effect of enamel matrix derivative (EMD) and hyaluronic acid (HA) and their synergistic combination on lipopolysaccharides (LPS)-induced inflammation in human keratinocytes and osteoblasts. MATERIAL AND METHODS: Cells were challenged with LPS (1 µg/ml) and cultured in the following treatment groups with EMD (30 mg/ml) and HA (30 mg/ml): LPS, EMD, HA, EMD + HA, EMD + LPS, HA + LPS, and EMD + HA + LPS. Cell viability, inflammatory cytokine expression, and cell migration were determined using colorimetric assay, quantitative real-time polymerase chain reaction (qPCR), and scratch wound healing assay, respectively. RESULTS: Cell viability was decreased when exposed to LPS compared to the controls. Overall, LPS treatment expressed upregulation on inflammatory cytokine tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). EMD and HA reduced up to 3.0-fold the cytokine expression caused by LPS (p < 0.05). EMD and HA statistically induced higher migration in osteoblasts and keratinocytes, respectively. Migration was impaired by LPS, whereas it significantly increased after addition of EMD and HA. CONCLUSIONS: EMD and HA are advantageous biomaterials that individually generate strong directional migratory keratinocyte and osteoblast response. Their combination also enhances cell viability, and anti-inflammatory and migratory abilities to promote healing specially under LPS inflammatory stimulus. Future in vivo and animal research is necessary to further characterize the effect of EMD and HA on periodontal regeneration. CLINICAL RELEVANCE: The use of EMD in conjunction with HA resulted in a reduction of inflammation and improvement of tissue healing at wound sites. Both biomaterials combined may potentially improve the effectiveness of bone regeneration in periodontal bone defects, pointing to the potential clinical relevance of both materials in regenerative periodontal surgery.

Cross-linked hyaluronic acid slows down collagen membrane resorption in diabetic rats through reducing the number of macrophages.

OBJECTIVES: We previously showed that accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated here its effect on the number of macrophages and endothelial cells (ECs) within the CM as a possible mechanism for inhibition of CM resorption. MATERIALS AND METHODS: Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS, and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and transglutaminase II, respectively. RESULTS: Diabetes increased the number of macrophages and ECs within the CMs (∼2.5-fold and fourfold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p < 0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. CONCLUSIONS: Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals. CLINICAL RELEVANCE: The combination of CLHA and CM may represent a valuable approach when guided tissue regeneration or guided bone regeneration procedures are performed in diabetic patients.