SARS-CoV-2 propagation in the world has led to rapid growth and an acceleration in the discoveries and publications of various interests. The main focus of a consistent number of studies has been the role of angiotensin-converting enzyme 2 (ACE2) in binding the virus and its role in expression of the inflammatory response after transmission. ACE2 is an enzyme involved in the renin–angiotensin system (RAS), whose key role is to regulate and counter angiotensin-converting enzyme (ACE), reducing the amount of angiotensin II and increasing angiotensin 1–7 (Ang1–7), making it a promising drug target for treating cardiovascular diseases. The classical RAS axis, formed by ACE, angiotensin II (Ang II), and angiotensin receptor type 1 (AT1), activates several cell functions and molecular signalling pathways related to tissue injury and inflammation. In contrast, the RAS axis composed of ACE2, Ang1–7, and Mas receptor (MasR) exerts the opposite effect concerning the inflammatory response and tissue fibrosis. Recent studies have shown the presence of the RAS system in periodontal sites where osteoblasts, fibroblasts, and osteoclasts are involved in bone remodelling, suggesting that the role of ACE2 might have a fundamental function in the under- or overexpression of cytokines such as interleukin-6 (IL-6), interleukin-7 (IL-7), tumour necrosis factor alpha (TNF-α), interleukin-2 (IL-2), interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta (TGF-β), associated with a periodontal disorder, mainly during coinfection with SARS-CoV-2, where ACE2 is underexpressed and cannot form the ACE2–Ang1–7–MasR axis. This renders the patient unresponsive to an inflammatory process, facilitating periodontal loss.

Aim: To evaluate the efficacy of recombinant human platelet-derived growth factor (rhPDGF)-BB combined with a cross-linked collagen matrix (CCM) for the treatment of multiple adjacent gingival recession type 1 defects (MAGRs) in combination with the coronally advanced flap (CAF).Materials and Methods: Thirty patients were enrolled in this triple-blind, randomized, placebo-controlled trial and treated with either CAF + CCM + rhPDGF, or CAF + CCM + saline. The primary outcome was mean root coverage (mRC) at 6 months.Complete root coverage, gain in gingival thickness (GT), keratinized tissue width, volumetric and ultrasonographic changes, and patient-reported outcome measures were also assessed. Mixed-modelling regression analyses were used for statistical comparisons.Results: At 6 months, the mRC of the CCM + rhPDGF and CCM alone groups were 88.25% and 77.72%, respectively (p = .02). A significant gain in GT was consistently observed for both treatment arms, and more so for the patients receiving the matrix containing rhPDGF through time (0.51 vs. 0.80 mm, on average, p = .01). The rhPDGF + CCM treated patients presented greater volume gain, higher soft tissue thickness, and a superior aesthetic score. Conclusion: rhPDGF enhances the clinical, volumetric, and aesthetic outcomes of MAGRs above the results achieved with CAF + CCM alone (ClinicalTrials.gov NCT04462237).

The aim of this study was to compare patient‐reported outcome measures (PROMs) of soft tissue substitutes versus autogenous grafts for soft tissue augmentation procedures at implant sites. Comprehensive and systematic literature searches were performed until December 2021. A focused question was formulated based on the Population, Intervention, Comparison and Outcome criteria (PICO): In patients with dental implants undergoing soft tissue augmentation (P), do soft tissue substitutes (I) compared to autogenous soft tissue graft (SCTG [subepithelial connective tissue graft]) (C) limit the post‐operative morbidity and other patient reported‐outcomes measures (O). Randomized controlled clinical trials, prospective‐, retrospective‐ and case‐series studies were included. Meta‐analyses were performed whenever possible and the results were expressed as weighted mean differences (WMD). A total of 29 clinical studies were included. For mucosal thickness gain, soft tissue substitutes significantly reduced the pain perception compared to SCTG (n = 4; WMD = 14.91 Visual Analog Scale [VAS] units; 95% confidence interval [CI] 6.42‐23.40; P < .0006) based on a 0‐100 VAS scale. Based on a 0‐10 VAS scale, a borderline significance of pain reduction was found when soft tissue substitutes were applied (n = 4; WMD = 1.62 VAS units; 95% CI 0.01‐3.23; P = .05). For keratinized tissue gain, soft tissue substitutes significantly reduced the pain perception after keratinized tissue augmentation compared to SCTG based on a 0‐100 VAS scale (n = 2; WMD = 21.43 VAS units; 95% CI 12.58‐30.28; P < .0001). Based on the 0‐10 VAS scale, soft tissue substitutes significantly reduced the pain as compared to SCTG (n = 4; WMD = 1.65 VAS units; 95% CI 0.66‐2.64; P = .001). Regarding pain medication, soft tissue substitutes required less painkillers (n = 6; WMD = 1.56 tablets; 95% CI 1.22‐1.91; P < .00001) after soft tissue augmentation. The surgery time was significantly reduced when soft tissue substitutes were used (n = 5; WMD = 10.9 minutes; 95% CI 4.60‐17.19; P < .00001). There were no significant differences in satisfaction, aesthetics, and quality of life (OHIP‐14) between soft tissue substitutes and autogenous grafts following soft tissue augmentation at implants sites. Soft tissue substitutes, compared to autogenous grafts, significantly improve PROMs following soft tissue augmentation at implant sites. Soft tissue substitutes can reduce pain perception, amounts of painkillers and surgery time while achieving similar levels of patient´s satisfaction as autogenous grafts without impairing the clinical outcomes. The current evidence indicates that they constitute a valid and reliable alternative to minimize the invasiveness in soft tissue augmentation procedures at implant sites.

The field of regeneration interventions in oral and maxillofacial surgeries still represents a challenge for researchers and clinicians. Understanding the biological and morphological behaviour of human cells towards the materials used for the regeneration surgeries is key to successfully choosing and applying the appropriate biomaterials for specific clinical situations. The aim of the study was the biological and morphological evaluation of autologous platelet concentrate materials obtained with different protocols, in culture with human periodontal ligament fibroblasts (HPLF). The study design included the evaluation of Leukocyte-Platelet-Rich-Fibrin (L-PRF), Concentrated Growth Factors (CGF) and autologous platelet gel (APG) in contact with the HPLF cell line after 24 h, 72 h and 7 days of in vitro culture. Cell proliferation and, therefore, viability were evaluated with XTT assays. The morphological response of the cells was evaluated by light microscopy, scanning electron microscopy and confocal microscopy. The XTT assay showed an interesting response in the growth curve. In particular, the material that gave the best results was the CGF. The morphological data supported the XTT assay, showing the best results for the CGF and L-PRF. In conclusion, all the platelet-derived materials stimulated the onset of the growth of the HPLF cell line, making them promising options for periodontal regeneration interventions.

Periodontal and peri-implant regeneration is the technique that aims to restore the damaged tissue around teeth and implants. They are surrounded by a different apparatus, and according to it, the regenerative procedure can differ for both sites. During the last century, several biomaterials and biological mediators were proposed to achieve a complete restoration of the damaged tissues with less invasiveness and a tailored approach. Based on relevant systematic reviews and articles searched on PubMed, Scopus, and Cochrane databases, data regarding different biomaterials were extracted and summarized. Bone grafts of different origin, membranes for guided tissue regeneration, growth factors, and stem cells are currently the foundation of the routinary clinical practice. Moreover, a tailored approach, according to the patient and specific to the involved tooth or implant, is mandatory to achieve a better result and a reduction in patient morbidity and discomfort. The aim of this review is to summarize clinical findings and future developments regarding grafts, membranes, molecules, and emerging therapies. In conclusion, tissue engineering is constantly evolving; moreover, a tailor-made approach for each patient is essential to obtain a reliable result and the combination of several biomaterials is the elective choice in several conditions.

Aim: To evaluate the efficacy of coronally advanced flap (CAF) versus tunnel technique (TUN) in covering isolated mid-facial peri-implant soft tissue dehiscences (PSTDs).Materials and Methods: Twenty-eight participants presenting with isolated nonmolar implants exhibiting PSTDs were enrolled and randomized to receive either CAF or TUN, both with a connective tissue graft (CTG). The primary outcome of the study was the percentage of mean PSTD coverage at 12 months. Secondary endpoints included the frequency of complete PSTD coverage, changes in keratinized mucosa width (KMW) and horizontal mucosal thickness (MT), as assessed with transgingival probing, 3D optical scanning and ultrasonography, professional aesthetic evaluation and patient-reported outcome measures (PROMs).Results: At 12 months, the mean PSTD coverage of the CAF and TUN groups was 90.23% and 59.76%, respectively (p = .03). CAF-treated sites showed a substantially higher frequency of complete PSTD coverage (p = .07), together with significantly greater gain of KMW (p = .01), increase in MT (p = .02), volumetric gain (p < .01) and professional aesthetic outcomes (p = .01). Both interventions showed an improvement in patient-reported aesthetics and a reduction of the anxiety related to the appearance of the implant compared to baseline, with the CAF group obtaining significantly higher scores (p = .03 for both PROMs).Conclusions: CAF + CTG resulted in superior PSTD coverage outcomes, greater gain in KMW and MT, and better PROMs than TUN + CTG for the treatment of isolated PSTDs (ClinicalTrials.gov NCT03498911).

In periodontitis patients, furcation defects are crucial sites to regenerate due to their complex anatomy. Various modern surgical techniques and use of biomaterials have been suggested in the literature. Among all, platelet-rich fibrin (PRF) has potential in tissue regeneration thanks to its role in the release of growth factors. Therefore, the purpose of this study was to evaluate the beneficial effect of the addition of PRF to open flap debridement (OFD) or as an adjuvant to other biomaterials such as bone grafts in the treatment of grade 2 mandibular furcation defects. Systematic research was carried out on the databases Medline, Scopus, Embase, and Cochrane Library and registered on PROSPERO (CRD42020167662). According to the PICO guidelines by Cochrane, randomized trials and prospective non-randomized trials were evaluated, with a minimum follow-up period of 6 months. The inclusion criteria were the absence of systemic diseases, non-smoking patients, and a population aged from 18 to 65 years. Vertical pocket probing depth (PPD), vertical clinical attachment level (VCAL), and gingival recession (REC) were the primary outcomes. Vertical furcation depth (VFD), and the percentage of bone defect fill (%v-BDF) were considered as secondary outcomes. A meta-analysis of the primary and secondary outcomes was performed. Publication bias was assessed through a funnel plot. Eighty-four articles were initially extracted. Eight randomized clinical trials were analyzed according to the exclusion and inclusion criteria. The Quality assessment instrument (QAI) revealed four articles at low risk of bias, one at moderate, and three at high risk of bias. The metanalysis showed significant data regarding PPD, VCAL, VFD and %v-BDF in the comparison between PRF + OFD vs. OFD alone. The adjunct of PRF to a bone graft showed a significant difference for VCAL and a not statistically significant result for the other involved parameters. In conclusion, the adjunctive use of PRF to OFD seems to enhance the periodontal regeneration in the treatment of grade 2 furcation defects. The combination of PRF and bone graft did not show better clinical results, except for VCAL, although the amount of literature with low risk of bias is scarce. Further well-designed studies to evaluate the combination of these two materials are therefore needed.

BackgroundThe aim of this study was to describe the application of high‐frequency ultrasonography (HFUS) for assessing keratinized mucosa (KM) width at implant sites.MethodsKM width was measured at 28 implant sites exhibiting a peri‐implant soft tissue dehiscence at baseline and 12 months after soft tissue augmentation. KM width assessment was performed with a periodontal probe [clinical assessment (clKM)] and with HFUS, based on the echointensity of the keratinized epithelium compared to the adjacent structures. KM width measurements on ultrasound scans were performed linearly (lnKM) and along the soft tissue profile [surface distance (sdKM)].ResultsNo statistically significant differences were observed between clKM, lnKM, and sdKM at baseline, while at 12 months, sdKM (5.313 ± 1.188 mm) was significantly higher than clKM (3.98 ± 1.25 mm) and lnKM (4.068 ± 1.197 mm) (P < 0.001 for both comparisons). A linear relationship between mucosal thickness (MT) and the difference between sdKM and lnKM was observed. In 95.2% of cases with MT > 2.51 mm, the discrepancy between sdKM and lnKM was at least 1 mm.ConclusionsHFUS is a noninvasive and valuable tool for measure KM width at implant site. Evaluating KM width along the soft tissue profile as a surface distance may improve the accuracy of the assessment.