Background: Periodontal disease negatively affects oral health-related quality of life (OHRQoL). While there is sufficient evidence for the clinical efficacy of periodontal therapy, data on patient-based outcomes are limited. Objectives: To systematically review the available evidence on the impact of periodontal therapy on OHRQoL in adults. Material & Methods: MEDLINE, EMBASE, CENTRAL and LILACS were searched without language restrictions. Longitudinal observational and intervention studies assessing changes in OHRQoL using validated measures, in adults with periodontal disease undergoing non-surgical (NST) or surgical therapy (ST), were eligible for inclusion. Study quality was assessed using the Newcastle-Ottawa scale and CONSORT-checklist. No meta-analysis was performed. Results: Eleven studies (seven prospective case-series', one controlled before-after study and three randomized controlled trials) of "medium" methodological quality were included in the review. All studies reported impaired OHRQoL before therapy. Nine studies reported a statistically significant improvement in OHRQoL after NST (follow-up = 1 week to 12 months, p < 0.05). The effect size for this improvement ranged from small (0.27) to large (0.8). No significant differences were reported between different forms of NST. Surgical therapy had a relatively lower impact on OHRQoL. A correlation between poor clinical response to therapy and poor OHRQoL outcomes was observed. Conclusion: Routine non-surgical therapy can moderately improve the OHRQoL in adults with periodontal disease.

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Thickened sinus membranes (>2 mm) and reduced residual ridge heights (≤4 mm) were highly prevalent in this sample of patients with missing posterior maxillary teeth. Membrane thickening >5 mm, especially of a polypoid type, is associated with an increased risk for ostium obstruction. In the presence of these findings, an ENT referral may be beneficial prior to implant-related sinus floor elevation.

Aim The objective of the present review was to answer the focused question: what is the effect of cell therapy in terms of orofacial bone regeneration compared to grafting with only biomaterial scaffolds and/or autogenous bone? Methods Electronic databases were searched for relevant controlled clinical and pre‐clinical (large‐animal) studies. Separate meta‐analyses of quantitative data regarding histological or radiographic new bone formation were performed. Results Forty‐seven eligible clinical and 57 pre‐clinical studies were included. Clinical studies were categorized based on the use of “minimally manipulated” whole tissues (e.g., bone marrow) or ex vivo expanded cells from “uncommitted” (bone marrow, adipose tissue) or “committed” sources (periosteum, bone). Based on limited and heterogeneous clinical evidence, implantation of cells (mostly whole bone marrow), in combination with biomaterial scaffolds results in bone regeneration which is (a) superior compared to implantation of scaffolds alone in sinus and horizontal ridge augmentation, and (b) comparable to autogenous bone in alveolar cleft repair. Conclusions Although current evidence points to the benefits of cell therapy in certain clinical indications, it is unclear whether the use of ex vivo expanded cells, either uncommitted or committed, is superior to whole tissue fractions in terms of bone regeneration. The relatively larger effect sizes in favour of cell therapy observed in pre‐clinical studies are diminished in clinical trials. Future controlled studies should include cost‐effectiveness analyses to guide clinical decision‐making.

Background Human platelet lysate (HPL) is emerging as the preferred xeno-free supplement for the expansion of mesenchymal stromal cells (MSCs) for bone tissue engineering (BTE) applications. Due to a growing demand, the need for standardization and scaling-up of HPL has been highlighted. However, the optimal storage time of the source material, i.e., outdated platelet concentrates (PCs), remains to be determined. The present study aimed to determine the optimal storage time of PCs in terms of the cytokine content and biological efficacy of HPL. Methods Donor-matched bone marrow (BMSCs) and adipose-derived MSCs (ASCs) expanded in HPL or fetal bovine serum (FBS) were characterized based on in vitro proliferation, immunophenotype, and multi-lineage differentiation. Osteogenic differentiation was assessed at early (gene expression), intermediate [alkaline phosphatase (ALP) activity], and terminal stages (mineralization). Using a multiplex immunoassay, the cytokine contents of HPLs produced from PCs stored for 1–9 months were screened and a preliminary threshold of 4 months was identified. Next, HPLs were produced from PCs stored for controlled durations of 0, 1, 2, 3, and 4 months, and their efficacy was compared in terms of cytokine content and BMSCs’ proliferation and osteogenic differentiation. Results BMSCs and ASCs in both HPL and FBS demonstrated a characteristic immunophenotype and multi-lineage differentiation; osteogenic differentiation of BMSCs and ASCs was significantly enhanced in HPL vs. FBS. Multiplex network analysis of HPL revealed several interacting growth factors, chemokines, and inflammatory cytokines. Notably, stem cell growth factor (SCGF) was detected in high concentrations. A majority of cytokines were elevated in HPLs produced from PCs stored for ≤ 4 months vs. > 4 months. However, no further differences in PC storage times between 0 and 4 months were identified in terms of HPLs’ cytokine content or their effects on the proliferation, ALP activity, and mineralization of BMSCs from multiple donors. Conclusions MSCs expanded in HPL demonstrate enhanced osteogenic differentiation, albeit with considerable donor variation. HPLs produced from outdated PCs stored for up to 4 months efficiently supported the proliferation and osteogenic differentiation of MSCs. These findings may facilitate the standardization and scaling-up of HPL from outdated PCs for BTE applications.

ObjectiveThe objective of the study was to systematically review the literature for studies reporting gene expression analyses (GEA) of the biological processes involved in early human peri-implant bone healing.MethodsElectronic databases (MEDLINE, EMBASE) were searched in duplicate. Controlled and uncontrolled studies reporting GEA of human peri-implant tissues - including ≥5 patients and ≥2 time points - during the first 4 weeks of healing were eligible for inclusion. Methodological quality and risk of bias were also assessed.ResultsFour exploratory studies were included in reporting GEA of either tissues attached to SLA or SLActive implants after 4 to 14 days or cells attached to TiOBlast or Osseospeed implants after 3 to 7 days. A total of 111 implants from 43 patients were analyzed using validated array methods; however, considerable heterogeneity and risk of bias were detected. A consistent overall pattern of gene expression was observed; genes representing an immuno-inflammatory response were overexpressed at days 3 to 4, followed by genes representing osteogenic processes at day 7. Genes representing bone remodeling, angiogenesis, and neurogenesis were expressed concomitantly with osteogenesis. Several regulators of these processes, such as cytokines, growth factors, transcription factors, and signaling pathways, were identified. Implant surface properties seemed to influence the healing processes at various stages via differential gene expression.ConclusionLimited evidence from gene expression studies in humans indicates that osteogenic processes commence within the first post-operative week and they appear influenced at various stages by implant surface properties.

Fetal bovine serum (FBS) is the most commonly used supplement for ex vivo expansion of human mesenchymal stem cells (hMSCs) for bone tissue engineering applications. However, from a clinical standpoint, it is important to substitute animal-derived products according to current good manufacturing practice (cGMP) guidelines. Humanized alternatives to FBS include three categories of products: human serum (HS), human platelet derivatives (HPDs)-including platelet lysate (PL) or platelet releasate (PR), produced by freeze/thawing or chemical activation of platelet concentrates, respectively, and chemically defined media (serum-free) (CDM). In this systematic literature review, the in vitro and in vivo osteogenic potential of hMSCs expanded in humanized (HS-, HPD-, or CDM-supplemented) media versus hMSCs expanded in FBS-supplemented media, was compared. In addition, PL and PR were compared in terms of their growth factor (GF)/cytokine-content and cell-culture efficacy. When using either 10-20% autologous or pooled HS, 3-10% pooled HPDs or CDM supplemented with GFs, in comparison with 10-20% FBS, a majority of studies reported similar or superior in vitro proliferation and osteogenic differentiation, and in vivo bone formation in ectopic or orthotopic rodent models. Moreover, a trend for higher GF content was observed in PL versus PR, although evidence for cell culture efficacy is limited. In summary, humanized supplements seem at least equally effective as FBS for hMSC expansion and osteogenic differentiation. Although pooled HPDs appear to be the most favorable supplement for large-scale hMSC expansion, further efforts are needed to standardize the preparation and composition of these products in compliance with cGMP standards.