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Theranostics 2023Increasing data reveals that gelatin that has been methacrylated is involved in a variety of physiologic processes that are important for therapeutic interventions.... (Review)
Review
Increasing data reveals that gelatin that has been methacrylated is involved in a variety of physiologic processes that are important for therapeutic interventions. Gelatin methacryloyl (GelMA) hydrogel is a highly attractive hydrogels-based bioink because of its good biocompatibility, low cost, and photo-cross-linking structure that is useful for cell survivability and cell monitoring. Methacrylated gelatin (GelMA) has established itself as a typical hydrogel composition with extensive biomedical applications. Recent advances in GelMA have focused on integrating them with bioactive and functional nanomaterials, with the goal of improving GelMA's physical, chemical, and biological properties. GelMA's ability to modify characteristics due to the synthesis technique also makes it a good choice for soft and hard tissues. GelMA has been established to become an independent or supplementary technology for musculoskeletal problems. Here, we systematically review mechanism-of-action, therapeutic uses, and challenges and future direction of GelMA in musculoskeletal disorders. We give an overview of GelMA nanocomposite for different applications in musculoskeletal disorders, such as osteoarthritis, intervertebral disc degeneration, bone regeneration, tendon disorders and so on.
Topics: Humans; Gelatin; Hydrogels; Tissue Engineering; Nanocomposites; Intervertebral Disc Degeneration
PubMed: 37064871
DOI: 10.7150/thno.80615 -
Clinics in Sports Medicine Jan 2020Meniscus injuries are among the most common athletic injuries and result in functional impairment in the knee. Repair is crucial for pain relief and prevention of...
Meniscus injuries are among the most common athletic injuries and result in functional impairment in the knee. Repair is crucial for pain relief and prevention of degenerative joint diseases like osteoarthritis. Current treatments, however, do not produce long-term improvements. Thus, recent research has been investigating new therapeutic options for regenerating injured meniscal tissue. This review comprehensively details the current methodologies being explored in the basic sciences to stimulate better meniscus injury repair. Furthermore, it describes how these preclinical strategies may improve current paradigms of how meniscal injuries are clinically treated through a unique and alternative perspective to traditional clinical methodology.
Topics: Adipose Tissue; Biomechanical Phenomena; Bone Marrow Cells; Cartilage; Chondrocytes; Humans; Intercellular Signaling Peptides and Proteins; Menisci, Tibial; Platelet-Rich Fibrin; Platelet-Rich Plasma; Regeneration; Stem Cell Transplantation; Synovial Membrane; Tibial Meniscus Injuries; Tissue Engineering; Tissue Scaffolds
PubMed: 31767102
DOI: 10.1016/j.csm.2019.08.003 -
World Journal of Gastroenterology Jul 2015To evaluate the efficacy of autologous bone marrow mononuclear cell transplantation in decompensated liver disease. (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the efficacy of autologous bone marrow mononuclear cell transplantation in decompensated liver disease.
METHODS
Medline, EMBASE, PubMed, Science Direct, and the Cochrane Library were searched for relevant studies. Retrospective case-control studies were included along with randomized clinical trials. Meta-analysis was performed in line with recommendations from the Cochrane Collaboration software review manager. Heterogeneity was assessed using a random-effects model.
RESULTS
Four randomized controlled trials and four retrospective studies were included. Cell transplantation increased serum albumin level by 1.96 g/L (95%CI: 0.74-3.17; P = 0.002], 2.55 g/L (95%CI: 0.32-4.79; P = 0.03), and 3.65 g/L (95%CI: 0.76-6.54; P = 0.01) after 1, 3, and 6 mo, respectively. Patients who had undergone cell transplantation also had a lower level of total bilirubin [mean difference (MD): -1.37 mg/dL; 95%CI: -2.68-(-0.06); P = 0.04] after 6 mo. This decreased after 1 year when compared to standard treatment (MD: -1.26; 95%CI: -2.48-(-0.03); P = 0.04]. A temporary decrease in alanine transaminase and aspartate transaminase were significant in the cell transplantation group. However, after 6 mo treatment, patients who had undergone cell transplantation had a slightly longer prothrombin time (MD: 5.66 s, 95%CI: 0.04-11.28; P = 0.05). Changes in the model for end-stage liver disease score and Child-Pugh score were not statistically significant.
CONCLUSION
Autologous bone marrow transplantation showed some benefits in patients with decompensated liver disease. However, further studies are still needed to verify its role in clinical treatment for end-stage liver disease.
Topics: Biomarkers; Bone Marrow Transplantation; Chi-Square Distribution; End Stage Liver Disease; Humans; Liver Function Tests; Odds Ratio; Risk Factors; Transplantation, Autologous; Treatment Outcome
PubMed: 26229412
DOI: 10.3748/wjg.v21.i28.8697 -
Current Oncology (Toronto, Ont.) Jul 2021This review aimed to evaluate the efficacy of oral cryotherapy in the prevention of chemotherapy-induced oral mucositis using meta-analysis and trial sequential... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review aimed to evaluate the efficacy of oral cryotherapy in the prevention of chemotherapy-induced oral mucositis using meta-analysis and trial sequential analysis, as well as to assess the quality of the results by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
METHODS
A comprehensive search of three databases including Medline, Embase and Central was performed to identify randomized controlled trials that used oral cryotherapy for the prevention of chemotherapy-induced oral mucositis. The primary outcome was the incidence of oral mucositis for trials employing oral cryotherapy as the intervention for the prevention of oral mucositis. The meta-analysis was performed using the random-effects model and random errors of the meta-analyses were detected by trial sequential analysis.
RESULTS
A total of 14 RCTs with 1577 participants were included in the present meta-analysis. Patients treated with oral cryotherapy were associated with a significantly lower risk of developing oral mucositis of any grade (risk ratio (RR), 0.67 (95% CI: 0.56-0.81, < 0.05)). Findings from the subgroup analyses showed that oral cryotherapy significantly reduced the risk of oral mucositis in patients undergoing bone marrow transplantation (RR 0.69, CI: 0.54-0.89, < 0.05) as well as chemotherapy (RR 0.66, CI: 0.58-0.75, < 0.05). Findings from the trial sequential analysis suggested that the evidence on oral cryotherapy as a preventive intervention for oral mucositis in patients with solid malignancies receiving conventional chemotherapy was conclusive.
CONCLUSION
Oral cryotherapy is effective in preventing oral mucositis in patients undergoing chemotherapy for the management of solid malignancies. The use of oral cryotherapy in preventing oral mucositis in bone marrow transplantation settings showed promising efficacy, but the evidence is not conclusive and requires more high-quality randomized controlled trials.
Topics: Antineoplastic Agents; Cryotherapy; Humans; Neoplasms; Stomatitis
PubMed: 34436016
DOI: 10.3390/curroncol28040250 -
The Cochrane Database of Systematic... Oct 2016There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients.
OBJECTIVES
The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions. The restrictive transfusion threshold uses a lower haemoglobin level to trigger transfusion (most commonly 7 g/dL or 8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin level to trigger transfusion (most commonly 9 g/dL to 10 g/dL).
SEARCH METHODS
We identified trials by searching CENTRAL (2016, Issue 4), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), the Transfusion Evidence Library (1950 to May 2016), the Web of Science Conference Proceedings Citation Index (1990 to May 2016), and ongoing trial registries (27 May 2016). We also checked reference lists of other published reviews and relevant papers to identify any additional trials.
SELECTION CRITERIA
We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered.
DATA COLLECTION AND ANALYSIS
We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two people extracted the data and assessed the risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as 'restrictive transfusion' and to the higher transfusion threshold as 'liberal transfusion'.
MAIN RESULTS
A total of 31 trials, involving 12,587 participants, across a range of clinical specialities (e.g. surgery, critical care) met the eligibility criteria. The trial interventions were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half of them used a 7 g/dL threshold, and the other half used a restrictive transfusion threshold of 8 g/dL to 9 g/dL. The trials were generally at low risk of bias .Some items of methodological quality were unclear, including definitions and blinding for secondary outcomes.Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 43% across a broad range of clinical specialties (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.49 to 0.65; 12,587 participants, 31 trials; high-quality evidence), with a large amount of heterogeneity between trials (I² = 97%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.97, 95% CI 0.81 to 1.16, I² = 37%; N = 10,537; 23 trials; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (high-quality evidence)). Liberal transfusion did not affect the risk of infection (pneumonia, wound, or bacteraemia).
AUTHORS' CONCLUSIONS
Transfusing at a restrictive haemoglobin concentration of between 7 g/dL to 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialities. There was no evidence that a restrictive transfusion strategy impacts 30-day mortality or morbidity (i.e. mortality at other points, cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. There were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, myocardial infarction, neurological injury/traumatic brain injury, acute neurological disorders, stroke, thrombocytopenia, cancer, haematological malignancies, and bone marrow failure. The findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.
Topics: Anemia; Erythrocyte Transfusion; Hematocrit; Hemoglobin A; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Reference Values; Transplantation, Autologous; Transplantation, Homologous
PubMed: 27731885
DOI: 10.1002/14651858.CD002042.pub4 -
Clinical Oral Implants Research Oct 2018A considerable portion of the adult population has received and/or is receiving treatment with antiresorptive drugs (ARDs). It is thus relevant to assess possible side... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
A considerable portion of the adult population has received and/or is receiving treatment with antiresorptive drugs (ARDs). It is thus relevant to assess possible side effects of ARD intake in connection to various aspects of implant therapy. The aim of this study was to answer the focused question "In patients with systemic intake of ARDs, what is the outcome and complication rate of implant therapy including associated bone grafting procedures comparing to patients without systemic intake of ARDs?"
MATERIALS AND METHODS
Original studies fulfilled predefined inclusion criteria (e.g., case series, cohort studies, case-control studies, and controlled and/or randomized controlled clinical trials; retro- or prospective design; and ≥10 patients with systemic intake of ARDs). Various patient-, medication-, and intervention-related parameters [i.e., implant loss, grafting procedure complication/failure, peri-implant marginal bone levels/loss, medication-related osteonecrosis of the jaws (MRONJ), and peri-implantitis] were extracted, and meta-analyses and quality assessment were performed.
RESULTS
Twenty-four studies with bisphosphonate (BP) intake (mainly low dose for osteoporosis treatment) and seven studies on hormone replacement therapy (HRT), including ≥10 patients, and controls not taking the medication were identified. Furthermore, seven studies on MRONJ associated with implants were included. Meta-analyses based on four studies reporting on patient level and eight studies reporting on implant level showed no significant differences in terms of implant loss between patients on BPs (mainly low dose for osteoporosis treatment) and controls. Furthermore, low-dose BP intake did not compromise peri-implant marginal bone levels. Based on two studies, no negative effect of HRT was observed on the implant level, while HRT appeared to exert a marginally significant negative effect regarding implant survival on the patient level and regarding peri-implant marginal bone levels. Based on six studies reporting single-patient data, MRONJ in patients on BP for osteoporosis appeared in 70% of the cases >36 months after start of drug intake, while in patients with cancer, MRONJ appeared in 64% of the cases ≤36 months after first BP intake.
CONCLUSION
Low-dose oral BP intake for osteoporosis treatment, in general, does not compromise implant therapy, that is, patients on ARDs do not lose more implants nor get more implant-related complications/failures comparing to implant patients without BP intake. There is almost no information available on the possible effect on implant therapy of high-dose BPs or other widely used ARDs (e.g., denosumab), or on the success or safety of bone grafting procedures. Patients with high-dose ARD intake for management of malignancies, patients on oral BP over a longer period of time, and patients with comorbidities should be considered as high-risk patients for MRONJ.
Topics: Bone Density Conservation Agents; Bone Transplantation; Dental Implantation, Endosseous; Dental Restoration Failure; Humans
PubMed: 30306695
DOI: 10.1111/clr.13282 -
Clinical Oral Implants Research Mar 2018The goal of Working Group 1 at the 2nd Consensus Meeting of the Osteology Foundation was to comprehensively assess the effects of soft tissue augmentation procedures on... (Review)
Review
Evidence-based knowledge on the aesthetics and maintenance of peri-implant soft tissues: Osteology Foundation Consensus Report Part 1-Effects of soft tissue augmentation procedures on the maintenance of peri-implant soft tissue health.
OBJECTIVES
The goal of Working Group 1 at the 2nd Consensus Meeting of the Osteology Foundation was to comprehensively assess the effects of soft tissue augmentation procedures on peri-implant health or disease.
MATERIALS AND METHODS
A systematic review and meta-analysis on the effects of soft tissue augmentation procedures included a total of 10 studies (mucosal thickness: n = 6; keratinized tissue: n = 4). Consensus statements, clinical recommendations, and implications for future research were based on structured group discussions and a plenary session approval.
RESULTS
Soft tissue grafting to increase the width of keratinized tissue around implants was associated with greater reductions in gingival and plaque indices when compared to non-augmented sites. Statistically significant differences were noted for final marginal bone levels in favor of an apically positioned flap plus autogenous graft vs. all standard-of-care control treatments investigated. Soft tissue grafting (i.e., autogenous connective tissue) to increase the mucosal thickness around implants in the aesthetic zone was associated with significantly less marginal bone loss over time, but no significant changes in bleeding on probing, probing depths, or plaque scores when compared to sites without grafting.
CONCLUSIONS
The limited evidence available supports the use of soft tissue augmentation procedures to promote peri-implant health.
Topics: Alveolar Ridge Augmentation; Connective Tissue; Consensus; Dental Implantation; Dental Implantation, Endosseous; Dental Implants; Gingiva; Humans; Jaw, Edentulous, Partially; Meta-Analysis as Topic; Mucous Membrane; Osteology; Surgical Flaps
PubMed: 29498127
DOI: 10.1111/clr.13110 -
Archives of Medical Research Jan 2021Human Mesenchymal Stem Cells (hMSCs) are multipotent stem cells capable of renewing themselves and differentiation in vitro into different kinds of tissues. In vivo...
INTRODUCTION
Human Mesenchymal Stem Cells (hMSCs) are multipotent stem cells capable of renewing themselves and differentiation in vitro into different kinds of tissues. In vivo hMSCs are sources of trophic factors modulating the immune system and inducing intrinsic stem cells to repair damaged tissues. Currently, there are multiple clinical trials (CT) using hMSCs for therapeutic purposes in a large number of clinical settings.
MATERIAL AND METHODS
The search strategy on clinicaltrials.gov has focused on the key term "Mesenchymal Stem Cells", and the inclusion and exclusion criteria were separated into two stages. Stage 1, CT on phases 1-4: location, the field of application, phase, and status. For stage 2, CT that have published outcome results: field of application, treatment, intervention model, source, preparation methods, and results.
RESULTS
By July 2020, there were a total of 1,138 registered CT. Most studies belong to either phase 2 (61.0%) or phase 1 (30.8%); most of them focused in the fields of traumatology, neurology, cardiology, and immunology. Only 18 clinical trials had published results: the most common source of isolation was bone marrow; the treatment varied from 1-200 M hMSCs; all of them have similar preparation methods; all of them have positive results with no serious adverse effects.
CONCLUSIONS
There appears to be a broad potential for the clinical use of hMSCs with no reported serious adverse events. There are many trials in progress, their future results will help to explore the therapeutic potential of these promising cellular sources of medicinal signals.
Topics: Cell Differentiation; Clinical Trials as Topic; Humans; Medicine; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 32977984
DOI: 10.1016/j.arcmed.2020.08.006 -
Journal of Periodontology Mar 2020Orthodontic treatment can greatly impact the periodontium, especially in dentitions with a thin periodontal phenotype. Orthodontic tooth movement can result into...
BACKGROUND
Orthodontic treatment can greatly impact the periodontium, especially in dentitions with a thin periodontal phenotype. Orthodontic tooth movement can result into iatrogenic sequelae to these vulnerable anatomic conditions, such as development and exacerbation of bony dehiscence or fenestration defects, which can manifest loss of periodontal support and gingival recession (GR). This systematic review aimed to investigate whether periodontal phenotype modification therapy (PhMT) involving hard tissue augmentation (PhMT-b) or soft tissue augmentation (PhMT-s) has clinical benefits for patients undergoing orthodontic treatment.
METHODS
An electronic search was performed in two major databases for journals published in English language from January 1975 to January 2019 and a hand search of printed journals was also performed to identify human clinical trials reporting clinical and radiographic outcomes of patients receiving orthodontic treatment with or without hard and soft tissue augmentation procedures. Data were extracted and organized into tables for qualitative assessment.
RESULTS
Eight studies were identified evaluating the outcomes of PhMT in patients undergoing orthodontic therapy. Six studies evaluated patients receiving PhMT-b via corticotomy-assisted orthodontic therapy (CAOT) and simultaneous bone augmentation while the other two received PhMT-s before tooth movement. No studies investigated PhMT-b alone without CAOT and most studies focused on the mandibular anterior decompensation movements. There was high heterogeneity in the study design and inconsistency of the reported outcomes; therefore, a meta-analysis was not performed. Evidence at this moment supports CAOT with hard tissue augmentation accelerated tooth movement. However, only two studies provided direct comparison to support that CAOT with PhMT-b reduced the overall treatment time compared with conventional orthodontic treatment. No periodontal complications or evidence of severe root resorption were reported for both groups. Four studies provided radiographic assessment of the PhMT-b and demonstrated increased radiographic density or thicker facial bone after the treatment. Two studies reported an expanded tooth movement. One study reported an increase in keratinized tissue width post-CAOT plus PhMT-b, while another study with a 10-year follow-up showed a lower degree of relapse using the mandibular irregularity index when compared with conventional tooth movement alone. Two studies examined the effect of PhMT-s before orthodontic treatment. Unfortunately, no conclusions can be drawn because of the limited number of studies with contradicting outcomes.
CONCLUSIONS
Within the limited studies included in this systematic review, PhMT-b via particulate bone grafting together with CAOT may provide clinical benefits such as modifying periodontal phenotype, maintaining or enhancing facial bone thickness, accelerating tooth movement, expanding the scope of safe tooth movement for patients undergoing orthodontic tooth movement. The benefits of PhMT-s alone for orthodontic treatment remain undetermined due to limited studies available. However, PhMT-b appears promising and with many potential benefits for patients undergoing orthodontic tooth movement. There is a need for a higher quality of randomized controlled trials or case control studies with longer follow-up to investigate the effects of different grafting materials and surgical sites other than mandibular anterior region.
Topics: Bone Transplantation; Gingival Recession; Humans; Phenotype; Root Resorption; Tooth Movement Techniques; United States
PubMed: 31670836
DOI: 10.1002/JPER.19-0037 -
Journal of Clinical Periodontology Mar 2021Systematic reviews have established the short-term improvements of periodontal regenerative/reconstructive procedures compared to conventional surgical treatment in... (Meta-Analysis)
Meta-Analysis
Medium- and long-term clinical benefits of periodontal regenerative/reconstructive procedures in intrabony defects: Systematic review and network meta-analysis of randomized controlled clinical studies.
BACKGROUND
Systematic reviews have established the short-term improvements of periodontal regenerative/reconstructive procedures compared to conventional surgical treatment in intrabony defects. However, a hierarchy of periodontal regenerative/reconstructive procedures regarding the medium- to long-term results of treatment does not exist.
AIM
To systematically assess the literature to answer the focused question "In periodontitis patients with intrabony defects, what are the medium- and long-term benefits of periodontal regenerative/reconstructive procedures compared with open flap debridement (OFD), in terms of clinical and/or radiographic outcome parameters and tooth retention?".
MATERIAL & METHODS
Randomized controlled clinical trials (RCTs), reporting on clinical and/or radiographic outcome parameters of periodontal regenerative/reconstructive procedures ≥3 years post-operatively, were systematically assessed. Clinical [residual probing pocket depth (PD) and clinical attachment level (CAL) gain, tooth loss] and radiographic [residual defect depth (RDD), bone gain (RBL)] outcome parameters were assessed. Descriptive statistics were calculated, and Bayesian random-effects network meta-analyses (NMA) were performed where possible.
RESULTS
Thirty RCTs, presenting data 3 to 20 years after treatment with grafting, GTR, EMD, as monotherapies, combinations thereof, and/or adjunctive use of blood-derived growth factor constructs or with OFD only, were included. NMA based on 21 RCTs showed that OFD was clearly the least efficacious treatment; regenerative/reconstructive treatments resulted in significantly shallower residual PD in 4 out 8 comparisons [range of mean differences (MD): -2.37 to -0.60 mm] and larger CAL gain in 6 out 8 comparisons (range of MD: 1.26 to 2.66 mm), and combination approaches appeared as the most efficacious. Tooth loss after regenerative/reconstructive treatment was less frequent (0.4%) compared to OFD (2.8%), but the evidence was sparse. There were only sparse radiographic data not allowing any relevant comparisons.
CONCLUSION
Periodontal regenerative/reconstructive therapy in intrabony defects results, in general, in shallower residual PD and larger CAL gain compared with OFD, translating in high rates of tooth survival, on a medium (3-5 years) to long-term basis (5-20 years). Combination approaches appear, in general, more efficacious compared to monotherapy in terms of shallower residual PD and larger CAL gain. A clear hierarchy could, however, not be established due to limited evidence.
Topics: Alveolar Bone Loss; Bone Transplantation; Dental Enamel Proteins; Follow-Up Studies; Guided Tissue Regeneration, Periodontal; Humans; Network Meta-Analysis; Periodontal Attachment Loss; Plastic Surgery Procedures; Treatment Outcome
PubMed: 33289191
DOI: 10.1111/jcpe.13409