Biodegradable metals for bone defect repair:A systematic review and meta-analysis based on animal studies

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.

Regulatory considerations for animal studies of biomaterial products

Animal studies play a vital role in validating the concept,feasibility,safety,performance and efficacy of biomaterials products during their bench-to-clinic translation.This article aims to share regulatory considerations for animal studies of biomaterial products.After briefly emphasizing the importance of animal studies,issues of animal studies during biomaterial products’translation are discussed.Animal studies with unclear purposes,flawed design and poor reporting quality could significantly reduce the translation efficiency and create regulatory challenges.Regulatory perspectives on the purpose,principle,quality and regulatory science of animal studies are also presented.Animal studies should have clear purposes,follow principles of 3R+DQ(replacement,reduction,refinement,design and quality)and execute under an efficiently operating quality management system.With the advancement of regulatory science,National Medical Products Administration of China has been developing a series of standards and guidance documents on animal studies of medical devices.Case studies of making decisions on whether to conduct animal studies are provided in the end with drug-eluting stents as examples.In summary,animal studies of biomaterial products should pay close attention to the rationale,design and quality in order to achieve their purposes.

Regulatory perspectives of combination products

Combination products with a wide range of clinical applications represent a unique class of medical products that are composed of more than a singular medical device or drug/biological product.The product research and development,clinical translation as well as regulatory evaluation of combination products are complex and challenging.This review firstly introduced the origin,definition and designation of combination products.Key areas of systematic regulatory review on the safety and efficacy of device-led/supervised combination products were then presented.Preclinical and clinical evaluation of combination products was discussed.Lastly,the research prospect of regulatory science for combination products was described.New tools of computational modeling and simulation,novel technologies such as artificial intelligence,needs of developing new standards,evidence-based research methods,new approaches including the designation of innovative or breakthrough medical products have been developed and could be used to assess the safety,efficacy,quality and performance of combination products.Taken together,the fast development of combination products with great potentials in healthcare provides new opportunities for the advancement of regulatory review as well as regulatory science.

对再生型疝修补补片动物试验设计的考量

再生型疝修补补片作为一种理想的疝和腹壁缺损修复医疗器械,对再生修复功效的评价是该类补片安全性和有效性的核心关键,与患者的疝复发直接相关。动物试验是疝修补补片再生功效评价的重要方法之一。结合多项已上市再生型疝补片动物研究及相关文献报道,本文对该类器械动物试验设计的各个要素进行了初步探讨并给出相关建议,供再生型疝修复生物材料的研发人员、动物试验研究人员、普通外科临床医生参考。