Research on the Opening of Adverse Drug Reaction Data in the EU

Systematically analyze the composition of post-marketing adverse drug reaction data and the open mode in the EU, and summarize its characteristics. EU post-marketing ADR data is open to six categories of stakeholders: EMA, EC, medicines regulatory authorities in EEA member states, healthcare professionals and the public, Marketing Authorization Holders, academia, WHO and medicines regulatory authorities in third countries. The EU has implemented hierarchical opening for ADRs, with different levels containing different data and facing different stakeholders. Openness is divided into active and passive openness. In opening up data, the EU complies with relevant personal data protection laws to protect the privacy of individuals. The EU’s post-marketing adverse drug reaction data openness is characterized by a combination of data openness and privacy protection, active and passive openness, and a hierarchy of data openness. It is hoped that this can provide a reference for the opening up of post-marketing adverse drug reaction data in China.

Biomaterials and regulatory science

The fast development of both biomaterials and regulatory science calls for a convergence,which is addressed in this article via their link through medical products of biomaterials and related safety and efficacy evaluation.The updated definition of biomaterials,and concepts of biomaterials-related medical products and so-called medical-grade and implantable materials are firstly introduced.Then a brief overview of the concept and history of regulatory science and its assessment of safety and efficacy of medical products,as well as the currently ongoing biomaterials-related regulatory science programs are presented.Finally,the opportunities provided by regulatory science for biomaterials as well as challenges on how to develop a biomaterials-based regulatory science system are discussed.As the first article in the field to elucidate the relationship between biomaterials and regulatory science,key take-home messages include(1)biomaterials alone are not medical products;(2)regulatory authorities approve/clear final medical products,not biomaterials;(3)there is no definition/regulation on the so-called medical-grade or implantable materials;and(4)safety and efficacy refer to final medical products,not biomaterials alone.

Tailored endothelialization enabled by engineered endothelial cell vesicles accelerates remodeling of small-diameter vascular grafts

Current gold standard for the replacement of small-diameter blood vessel(ID<4 mm)is still to utilize the autologous vessels of patients due to the limitations of small-diameter vascular grafts(SDVG)on weak endothelialization,intimal hyperplasia and low patency.Herein,we create the SDVG with the tailored endothelialization by applying the engineered endothelial cell vesicles to camouflaging vascular grafts for the enhancement of vascular remodeling.The engineered endothelial cell vesicles were modified with azide groups(ECVs-N3)through metabolic glycoengineering to precisely link the vascular graft made of PCL-DBCO via click chemistry,and thus fabricating ECVG(ECVs-N3 modified SDVG),which assists inhibition of platelet adhesion and activation,promotion of ECs adhesion and enhancement of anti-inflammation.Furthermore,In vivo single-cell transcriptome analysis revealed that the proportion of ECs in the cell composition of ECVG surpassed that of PCL,and the tailored endothelialization enabled to convert endothelial cells(ECs)into some specific ECs clusters.One of the specific cluster,Endo_C5 cluster,was only detected in ECVG.Consequently,our study integrates the engineered membrane vesicles of ECVs-N3 from native ECs for tailored endothelialization on SDVG by circumventing the limitations of living cells,and paves a new way to construct the alternative endothelialization in vessel remodeling following injury.

Mild synthesis of ultra-bright carbon dots with solvatochromism for rapid lipid droplet monitoring in varied physiological processes

Lipid droplets(LDs)participating in various cellular activities and are increasingly being emphasized.Fluorescence imaging provides powerful tool for dynamic tracking of LDs,however,most current LDs probes remain inconsistent performance such as low Photoluminescence Quantum Yield(PLQY),poor photostability and tedious washing procedures.Herein,a novel yellow-emissive carbon dot(OT-cD)has been synthesized conveniently with high PLQY up to 90%.Besides,OT-CD exhibits remarkable amphiphilicity and solvatochromic property with lipid-water partition coefficient higher than 2,which is much higher than most LDs probes.These characters enable OT-CD high brightness,stable and wash-free LDs probing,and feasible for in vivo imaging.Then,detailed observation of LDs morphological and polarity variation dynamically in different cellular states were recorded,including ferroptosis and other diseases processes.Furthermore,fast whole imaging of zebrafish and identifed LD enrichment in injured liver indicate its further feasibility for in vivo application.In contrast to the reported studies to date,this approach provides a versatile conventional synthesis system for high-performance LDs targeting probes,combing the advantages of easy and high-yield production,as well as robust brightness and stability for long-term imaging,facilitating investigations into organelle interactions and LD-associated diseases.

A regulatory perspective on recombinant collagen-based medical devices

As a class of novel biomaterials manufactured by synthetic biology technologies,recombinant collagens are candidates for a variety of medical applications.In this article,a regulatory scientific perspective on recombinant collagens and their medical devices is presented with a focus on the definition,translation,classification and technical review.Recombinant collagens are categorized as recombinant human collagen,recombinant humanized collagen and recombinant collagen-like protein,as differentiated by specific compositions and structures.Based on their intended uses and associated risks,recombinant collagen-based medical devices are generally classified as Class Ⅱ or Ⅲ in China.The regulatory review of recombinant collagen-based medical devices aims to assess their safety and efficacy demonstrated by scientific evidences generated from preclinical and clinical evaluations.Taken together,opportunities as well as challenges for their future clinical translation of recombinant collagen-based medical devices abound,which highlights the essential role of regulatory science to provide new tools,standards,guidelines and methods to evaluate the safety and efficacy of medical products.

Magnetofection:Magic magnetic nanoparticles for efficient gene delivery

Magnetic nanoparticles(MNPs)have become a research hotspot and widely used in the biomedical field in recent decades due to their unique magnetic properties.This minireview summarizes the specific gene transfection of magnetic particles(magnetofection)during eversy dynamic process of gene delivery(gene binding,cellular uptake,endosomal escape,intracellular trafficking and in vivo targeting).Meanwhile,the synergistic biomedical application of magnetofection and the effects of MNPs have also been discussed,including magnetic resonance imaging(MRI),magnetic mediated hyperthermia(MMH),Fenton reaction and autophagy.Finally,the clinical prospect of magnetofection was briefly expected.

Translation of biomaterials from bench to clinic

Scientific research originates from curiosity and interests. Translational research of biomaterials should always focus on addressing specific needs of the targeted clinical applications. The guest editors of this special issue hope that the included articles have provided cutting-edge biomaterials research as well as insights of the translation of biomaterials from bench to clinic.

A review of hydrogels used in endoscopic submucosal dissection for intraoperative submucosal cushions and postoperative management

Endoscopic submucosal dissection(ESD)has been clinically proved to have prominent advantages in the treatment of early gastrointestinal cancers over traditional surgery,including less trauma,fewer complications,a quicker recovery and lower costs.During the procedure of ESD,appropriate and multifunctional submucosal injected materials(SIMs)as submucosal cushions play an important role,however,even with many advances in design strategies of SIMs over the past decades,the performance of the submucosal cushions with postoperative management function seems to be still unsatisfactory.In this review,we gave a brief historical recount about the clinical development of SIMs,then some common applications of hydrogels used as SIMs in ESD were summarized,while an account of the universal challenges during ESD procedure was also outlined.Going one step further,some cutting-edge functional strategies of hydrogels for novel applications in ESD were exhibited.Finally,we concluded the advantages of hydrogels as SIMs for ESD as well as the treatment dilemma clinicians faced when it comes to deeply infiltrated lesions,some technical perspectives about linking the clinical demand with commercial supply were also proposed.Encompassing the basic elements of SIMs used in ESD surgery and the corresponding postoperative management requirements,this review could be a good reference for relevant practitioners in expanding the research horizon and improving the well-being index of patients.

Fabrication and evaluation of an optimized xenogenic decellularized costal cartilage graft:preclinical studies of a novel biocompatible prosthesis for rhinoplasty

On account of the poor biocompatibility of synthetic prosthesis,millions of rhinoplasty recipients have been forced to choose autologous costal cartilage as grafts,which suffer from limited availability,morbidity at the donor site and prolonged operation time.Here,as a promising alternative to autologous costal cartilage,we developed a novel xenogeneic costal cartilage and explored its feasibility as a rhinoplasty graft for the first time.Adopting an improved decellularization protocol,in which the ionic detergent was substituted by trypsin,the resulting decellularized graft was confirmed to preserve more structural components and better mechanics,and eliminate cellular components effectively.The in vitro and in vivo compatibility experiments demonstrated that the decellularized graft showed excellent biocompatibility and biosecurity.Additionally,the functionality assessment of rhinoplasty was performed in a rabbit model,and the condition of grafts after implantation was comprehensively evaluated.The optimized graft exhibited better capacity to reduce the degradation rate and maintain the morphology,in comparison to the decellularized costal cartilage prepared by conventional protocol.These findings indicate that this optimized graft derived from decellularized xenogeneic costal cartilage provides a new prospective for future investigations of rhinoplasty prosthesis and has great potential for clinical application.

Actuation performances of catkin fibers reinforced thiol-acrylate main-chain liquid crystalline elastomer

Liquid crystalline elastomers(LCEs)have been utilized as an important class of smart actuator materials.However,the modest actuation mechanical and robustness performances remain a challenge.Inspired by the specific structures,well mechanical properties and physico-chemical characteristics of some natural plant fibers,a composite of thiol-acrylate main-chain LCE matrix incorporated with catkin fibers is designed and developed.The catkin fibers build a network as reinforcement phase,and demon-strate effective compatibility and integration property with the matrix,their high flexibility can be adapted to the large deforma-tional performance of LCE matrix.The prepared LCE composite demonstrates strong mechanical actuation properties.The mod-ulus and driving force triggered by the stimuli are obviously increased.The tensile strength and fatigue failure resistant prop-erty under high loadings and repeated cycles of thermal actua-tion or photothermal actuation are greatly enhanced.While the stimulus response deformation rate,phase transition temperature and liquid crystal phase structure of the LCE matrix,and so on,do not weaken or change.This work promotes the LCE materi-als’application potential and broadens the application value of natural plant fibers.

Zn/Sr dual ions-collagen co-assembly hydroxyapatite enhances bone regeneration through procedural osteo-immunomodulation and osteogenesis

The immune microenvironment induced by biomaterials played vital roles in bone regeneration.Hydroxyapatite(HA)and its ion-substituted derivates represent a large class of core inorganic materials for bone tissue engineering.Although ion substitution was proved to be a potent way to grant HA more biological functions,few studies focused on the immunomodulatory properties of ion-doped HA.Herein,to explore the potential osteoimmunomodulatory effects of ion-doped HA,zinc and strontium co-assembled into HA through a collagen template biomimetic way(ZnSr-Col-HA)was successfully achieved.It was found that ZnSr-Col-HA could induce a favorable osteo-immune microenvironment by stimulating macrophages.Furthermore,ZnSr-Col-HA demonstrated a procedural promoting effect on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.Specifically,the osteo-immune microenvironment acted as a dominant factor in promoting osteogenic gene expressions at the early stage through OSM signal pathway.Whereas the direct stimulating effects on BMSCs by Zn^(2+)/Sr^(2+) were more effectively at the later stage with Nfatc1/Maf and Wnt signals activated.In vivo study confirmed strong promoting effects of ZnSr-Col-HA on critical-sized cranial defect repair.The current study indicated that such a combined biomaterial design philosophy of dual ion-doping and biomimetic molecular co-assembly to endow HA applicable osteoimmunomodulatory characteristics might bring up a new cutting-edge concept for bone regeneration study.

Sterilization and disinfection methods for decellularized matrix materials:Review,consideration and proposal

Sterilization is the process of killing all microorganisms,while disinfection is the process of killing or removing all kinds of pathogenic microorganisms except bacterial spores.Biomaterials involved in cell experiments,animal experiments,and clinical applications need to be in the aseptic state,but their physical and chemical properties as well as biological activities can be affected by sterilization or disinfection.Decellularized matrix(dECM)is the low immunogenicity material obtained by removing cells from tissues,which retains many inherent components in tissues such as proteins and proteoglycans.But there are few studies concerning the effects of sterilization or disinfection on dECM,and the systematic introduction of sterilization or disinfection for dECM is even less.Therefore,this review systematically introduces and analyzes the mechanism,advantages,disadvantages,and applications of various sterilization and disinfection methods,discusses the factors influencing the selection of sterilization and disinfection methods,summarizes the sterilization and disinfection methods for various common dECM,and finally proposes a graphical route for selecting an appropriate sterilization or disinfection method for dECM and a technical route for validating the selected method,so as to provide the reference and basis for choosing more appropriate sterilization or disinfection methods of various dECM.

Injectable bone cement with magnesium-containing microspheres enhances osteogenesis via anti-inflammatory immunoregulation

Injectable bone cement is especially useful in minimally invasive surgeries to repair small and irregular bone defects.Amongst different kinds of injectable bone cements,bioactive calcium phosphate bone cement(CPC)has been widely studied due to its biological activity.However,its dense structure and poor biodegradability prevent the ingrowth of living tissue,which leads to undesirable bone regeneration and clinical translation.To address this issue,we prepared bone cement based on Magnesium-containing microspheres(MMSs)that can not only be cured into a 3D porous scaffold but also have controllable biodegradability that continuously provides space for desired tissue ingrowth.Interestingly,magnesium ions released from MMSs cement(MMSC)trigger positive immunomodulation via upregulation of the anti-inflammatory genes IL-10 and M2 macrophage polarization with increased expression of CD206,which is beneficial to osteogenesis.Moreover,the physicochemical properties of MMSC,including heat release,rheology and setting time,can be tuned to meet the requirements of injectable bone cement for clinical application.Using a rat model,we have demonstrated that MMSC promoted osteogenesis via mediation of tissue ingrowth and anti-inflammatory immunomodulation.The study provides a paradigm for the design and preparation of injectable bone cements with 3D porous structures,biodegradability and anti-inflammatory immunoregulation to efficiently promote osteogenesis.

Evidence-based biomaterials research

The fast development of biomaterials science and engineering has generated significant number of studies and publications as well as tremendous amount of research data.A methodology is needed to translate such research data and results to validated scientific evidence.This article for the first time proposes the concept and methodology of evidence-based biomaterials research,which is to use evidence-based research approach represented by systematic reviews to generate evidence for answering scientific questions related to biomaterials.After briefly introducing the advancement of biomaterials since 1950s,the scientific and engineering nature of biomaterials are discussed along with the roadmap of biomaterials translation from basic research to commercialized medical products,and the needs of scientific evidence.Key information of the evidence-based approach such as its origination from evidence-based medicine,levels of evidence,systematic review and meta-analysis,differences between systematic and narrative reviews is then highlighted.Applications with a step-by-step procedure of conducting evidence-based biomaterials research,three examples of biomaterials research using evidence-based approach to generate scientific evidence,and opportunities and challenges of evidence-based biomaterials research are presented.With its notable impact on the practice of medicine,the evidence-based approach is also expected to make influential contributions to the biomaterials field.