Biodegradable metals are promising candidates for bone defect repair. With an evidence-based approach, this study investigated and analyzed the performance and degradation properties of biodegradable metals in animal models for bone defect repair to explore their potential clinical translation. Animal studies on bone defect repair with biodegradable metals in comparison with other traditional biomaterials were reviewed. Data was carefully collected after identification of population, intervention, comparison, outcome, and study design (PICOS), and following the inclusion criteria of biodegradable metals in animal studies. 30 publications on pure Mg, Mg alloys, pure Zn and Zn alloys were finally included after extraction from a collected database of 2543 publications. A qualitative systematic review and a quantitative meta-analysis were performed. Given the heterogeneity in animal model, anatomical site and critical size defect (CSD), biodegradable metals exhibited mixed effects on bone defect repair and degradation in animal studies in comparison with traditional non-degradable metals, biodegradable polymers, bioceramics, and autogenous bone grafts. The results indicated that there were limitations in the experimental design of the included studies, and quality of the evidence presented by the studies was very low. To enhance clinical translation of biodegradable metals, evidence-based research with data validity is needed. Future studies should adopt standardized experimental protocols in investigating the effects of biodegradable metals on bone defect repair with animal models.

Objective: The optimal therapeutic strategies of stem cells for spinal cord injury (SCI) are fully explored in animal studies to promote the translation of preclinical findings to clinical practice, also to provide guidance for future animal experiments and clinical studies.Methods: PubMed, Web of Science, Embase, CNKI, Wangfang, VIP, and CBM were searched from inception to September 2021. Screening of search results, data extraction, and references quality evaluation were undertaken independently by two reviewers.Results and Discussion: A total of 188 studies were included for data analysis. Results of traditional meta-analysis showed that all 15 diverse types of stem cells could significantly improve locomotor function of animals with SCI, and results of further network meta-analysis showed that adipose-derived mesenchymal stem cells had the greatest therapeutic potential for SCI. Moreover, a higher dose (≥1 × 106) of stem cell transplantation had better therapeutic effect, transplantation in the subacute phase (3–14 days, excluding 3 days) was the optimal timing, and intralesional transplantation was the optimal route. However, the evidence of current animal studies is of limited quality, and more high-quality research is needed to further explore the optimal therapeutic strategies of stem cells, while the design and implementation of experiments, as well as measurement and reporting of results for animal studies, need to be further improved and standardized to reduce the risk when the results of animal studies are translated to the clinic.Systematic Review Registration: [website], identifier [registration number].

Background How much scientific evidence is there to show that stem cell therapy is sufficient in preclinical and clinical studies of spinal cord injury before it is translated into clinical practice? This is a complicated problem. A single, small-sample clinical trial is difficult to answer, and accurate insights into this question can only be given by systematically evaluating all the existing evidence. Methods The PubMed, Ovid-Embase, Web of Science, and Cochrane databases were searched from inception to February 10, 2022. Two independent reviewers performed the literature search, identified and screened the studies, and performed a quality assessment and data extraction. Results In total, 62 studies involving 2439 patients were included in the analysis. Of these, 42 were single-arm studies, and 20 were controlled studies. The meta-analysis showed that stem cells improved the ASIA impairment scale score by at least one grade in 48.9% [40.8%, 56.9%] of patients with spinal cord injury. Moreover, the rate of improvement in urinary and gastrointestinal system function was 42.1% [27.6%, 57.2%] and 52.0% [23.6%, 79.8%], respectively. However, 28 types of adverse effects were observed to occur due to stem cells and transplantation procedures. Of these, neuropathic pain, abnormal feeling, muscle spasms, vomiting, and urinary tract infection were the most common, with an incidence of > 20%. While no serious adverse effects such as tumorigenesis were reported, this could be due to the insufficient follow-up period. Conclusions Overall, the results demonstrated that although the efficacy of stem cell therapy is encouraging, the subsequent adverse effects remain concerning. In addition, the clinical trials had problems such as small sample sizes, poor design, and lack of prospective registration, control, and blinding. Therefore, the current evidence is not sufficiently strong to support the clinical translation of stem cell therapy for spinal cord injury, and several problems remain. Additional well-designed animal experiments and high-quality clinical studies are warranted to address these issues.

Biodegradable metals hold promises for bone fracture repair. Their clinical translation requires pre-clinical evaluations including animal studies, which demonstrate the safety and performance of such materials prior to clinical trials. This evidence-based study investigates and analyzes the performance of bone fractures repair as well as degradation properties of biodegradable metals in animal models. Data were carefully collected after identification of population, interventions, comparisons, outcomes and study design, as well as inclusion criteria combining biodegradable metals and animal study. Twelve publications on pure Mg, Mg alloys and Zn alloys were finally included and reviewed after extraction from a collected database of 2122 publications. Compared to controls of traditional non-degradable metals or resorbable polymers, biodegradable metals showed mixed or contradictory outcomes of fracture repair and degradation in animal models. Although quantitative meta-analysis cannot be conducted because of the data heterogeneity, this systematic review revealed that the quality of evidence for biodegradable metals to repair bone fractures in animal models is ‘very low’. Recommendations to standardize the animal studies of biodegradable metals were proposed. Evidence-based biomaterials research could help to both identify reliable scientific evidence and ensure future clinical translation of biodegradable metals for bone fracture repair.

Objective. Chronological age alone does not adequately reflect the difference in health status of a patient with hypertension. Frailty is closely associated with biological age, and its assessment is clinically useful in addressing the heterogeneity of health status. The purpose of our study is to comprehensively examine the predictive value of frailty for negative health outcomes in hypertensive patients through a systematic review and meta-analysis. Methods. Multiple English and Chinese databases were searched from inception to 04.11.2020. All cross-sectional and longitudinal studies that examined the association between frailty and relevant clinical outcomes among hypertensive patients were included. The NOS was used to assess the risk of bias of studies included in the analysis. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were pooled for outcomes associated with frailty. Results. Six longitudinal studies and one cross-sectional study involving 17403 patients with hypertension were included in the meta-analysis. The risk of bias of all included studies was rated as low or moderate. The pooled HR of frailty related to mortality was 2.45 (95% CI: 2.08-2.88). The pooled HR of prefrailty and frailty-related injurious falls was 1.07 (95% CI: 0.83-1.37) and 1.89 (95% CI: 1.56-2.27), respectively. The pooled HR of prefrailty and frailty-related hospitalization was 1.54 (95% CI: 1.38-1.71) and 1.94 (95% CI: 1.17-3.24), respectively. Conclusions. This systematic review suggests that frailty was a strong predictor of mortality, hospitalization, and injurious falls among patients with hypertension. Our findings indicate that assessment of frailty in patients with hypertension to guide their management may be necessary in clinical setting. However, our finding was based on very limited amount studies; thus, future studies are required to further validate the role of frailty in prediction of negative health outcomes in hypertensive patients as well as pay more attention to the following knowledge gaps: (1) the association between frailty and hypertension-related outcomes, (2) the significance of the association between different frailty models and relevant clinical outcomes, and (3) the predictive value of prefrailty for the negative health outcomes in people with hypertension.