Perspectives on systematic capacity building in pharmaceutical regulation for regulators of medical products.

Having a robust, integrated regulatory system is important for ensuring the availability of safe and efficacious medical products of good quality and for protecting public health. However, less than 30% of countries globally have reached the required regulatory maturity level three, with low- and middle-income countries facing challenges in attracting and retaining qualified staff. World Health Organization (WHO) advocates for systematic workforce development, including competency-based education, to address these gaps. We provide perspectives on a systematic approach to capacity building of medicine regulators based on the experience and lessons learnt in developing and piloting the WHO global competency framework for medicine regulators through three scenarios. A systematic approach to capacity building, such as the human performance technology model, can be used to implement the WHO competency framework as part of organizational performance improvement while ensuring that initiatives are well-defined, targeted, and aligned with organizational goals. The competency framework can be used in different contexts, such as improving organization performance for individual regulatory authorities, strengthening regional collaborations, harmonization and reliance on medical products assessment and joint good manufacturing practices inspections of pharmaceutical manufacturers, and developing learning programs for medicine regulators. A competency-based learning approach for regulatory professionals ensures the transfer of learning to the workplace by integrating real-world practices in learning activities and assessments. Further work is required to develop and validate the assessment instruments, apply the competency framework in other contexts, expanding the learning programmes while continuously providing feedback for further refinement of the competency framework and implementation support tools.

Selenium Nanoparticle Activity against S. mutans Biofilms as a Potential Treatment Alternative for Periodontitis.

The disruption of periodontal biofilms and prevailing antimicrobial resistance issues continue to pose a great challenge to the treatment of periodontitis. Here, we report on selenium nanoparticles (SeNPs) as a treatment alternative for periodontitis by determining their antibiofilm activity against S. mutans biofilms and the potential role of particle size in disrupting biofilms. SeNPs were synthesised via a reduction reaction. Various physicochemical characterisations were conducted on the NPs, including size and shape. The microbroth dilution method was used to conduct the biofilm and antibiofilm assay against S. mutans, which was analysed by absorbance. SeNPs displayed hydrodynamic sizes as low as 46 ± 4 nm at a volume ratio of 1:5 (sodium selenite/ascorbic acid) with good monodispersity and stability. Hydrodynamic sizes of SeNPs after resuspension in tryptic soy broth supplemented with 2.5% sucrose (TSB + 2.5% suc.) and incubated at 37 °C for 24 h, ranged from 112 to 263 nm, while the zeta potential values increased to greater than -11 mV. The biofilm assay indicated that S. mutans are weakly adherent, bordering on moderately adherent biofilm producers. The minimum biofilm inhibitory concentration (MBIC) was identified at 500 µg/mL. At a 1000 µg/mL concentration, SeNPs were able to inhibit S. mutan biofilms up to 99.87 ± 2.41% at a volume ratio of 1:1. No correlation was found between antibiofilm activity and particle size; however, antibiofilm activity was proven to be concentration-dependant. SeNPs demonstrate antibiofilm activity and may be useful for further development in treating periodontitis.

The process of ratifying the treaty to establish the African Medicines Agency: perspectives of national regulatory agencies.

The vision of the African Medicines Agency (AMA) is to ensure that all Africans have access to affordable medical products that meet internationally recognized standards of quality, safety and efficacy for priority diseases/conditions. The AMA is being established by a treaty which had to be ratified by a minimum of 15 African countries. Although there was no deadline, the ratification process has been slower than expected. This study therefore analysed the rationale, perceived benefits, enabling factors and challenges of the AMA's establishment. This study was a qualitative, cross-sectional, census survey of the national medicines regulatory authorities (NRAs) of 45 African countries. The Heads of NRAs and a senior NRA staff member were contacted to complete self-administered questionnaires. The existence of mature NRAs, the desire to have harmonized regulatory systems, the presence of strong political will and appropriate advocacy to expedite treaty signing are all enabling factors for AMA treaty signing. The challenges reported include the fact that the process is slow and there is limited understanding of the process. Competing national priorities, changes in office bearers in the public system and stagnation of the process at the ministerial level were also challenges reported. This study has improved the understanding of the treaty signing and ratification process and the perceived benefits and enabling factors of signing and ratification from African NRAs' perspective. NRAs also highlighted challenges encountered in the process. Addressing these challenges will result in effective medicines regulation by galvanizing technical support, regulatory expertise and resources at a continental level.

Ionome mapping and amino acid metabolome profiling of Phaseolus vulgaris L. seeds imbibed with computationally informed phytoengineered copper sulphide nanoparticles.

This study reports the effects of a computationally informed and avocado-seed mediated Phyto engineered CuS nanoparticles as fertilizing agent on the ionome and amino acid metabolome of Pinto bean seeds using both bench top and ion beam analytical techniques. Physico-chemical analysis of the Phyto engineered nanoparticles with scanning-electron microscopy, transmission electron microscopy, X-ray diffraction, and Fourier Transform Infrared Spectroscopy confirmed the presence of CuS nanoparticles. Molecular dynamics simulations to investigate the interaction of some active phytocompounds in avocado seeds that act as reducing agents with the nano-digenite further showed that 4-hydroxybenzoic acid had a higher affinity for interacting with the nanoparticle's surface than other active compounds. Seeds treated with the digenite nanoparticles exhibited a unique ionome distribution pattern as determined with external beam proton-induced X-ray emission, with hotspots of Cu and S appearing in the hilum and micropyle area that indicated a possible uptake mechanism via the seed coat. The nano-digenite also triggered a plant stress response by slightly altering seed amino acid metabolism. Ultimately, the nano-digenite may have important implications as a seed protective or nutritive agent as advised by its unique distribution pattern and effect on amino acid metabolism.

Minimum Information for Conducting and Reporting In Vitro Intracellular Infection Assays.

Bacterial pathogens are constantly evolving to outsmart the host immune system and antibiotics developed to eradicate them. One key strategy involves the ability of bacteria to survive and replicate within host cells, thereby causing intracellular infections. To address this unmet clinical need, researchers are adopting new approaches, such as the development of novel molecules that can penetrate host cells, thus exerting their antimicrobial activity intracellularly, or repurposing existing antibiotics using nanocarriers (i.e., nanoantibiotics) for site-specific delivery. However, inconsistency in information reported across published studies makes it challenging for scientific comparison and judgment of experiments for future direction by researchers. Together with the lack of reproducibility of experiments, these inconsistencies limit the translation of experimental results beyond pre-clinical evaluation. Minimum information guidelines have been instrumental in addressing such challenges in other fields of biomedical research. Guidelines and recommendations provided herein have been designed for researchers as essential parameters to be disclosed when publishing their methodology and results, divided into four main categories: (i) experimental design, (ii) establishing an in vitro model, (iii) assessment of efficacy of novel therapeutics, and (iv) statistical assessment. These guidelines have been designed with the intention to improve the reproducibility and rigor of future studies while enabling quantitative comparisons of published studies, ultimately facilitating translation of emerging antimicrobial technologies into clinically viable therapies that safely and effectively treat intracellular infections.

Nanophytomedicines as Therapeutic Agents for Parkinson's Disease.

Phytochemicals are promising therapeutics for various neurodegenerative disorders, including Parkinson's disease (PD). However, their efficacy, pharmacokinetic properties, and penetration across the blood-brain barrier can be improved using delivery systems such as nanoparticles. We reviewed recently published work in which nanoparticles were used to deliver phytochemicals toward PD treatment. The studies show that nanoparticles not only improve the pharmacological effect of the phytochemicals but also enable targeting to the brain and crossing of the blood-brain barrier. Various ligands were added to the nanoparticles to improve blood-brain barrier transportation. The promising findings from the published studies reveal that more research into nanophytomedicine approaches as therapeutic targets for PD is warranted, especially since they have the potential to protect against key features of PD, including α-synuclein aggregation, mitochondrial dysfunction, and dopaminergic neuronal death. Furthermore, future directions should involve smart designs to tailor nanoparticles for improved therapeutic delivery by modifying their features, such as architecture, surface and material properties, targeting ligands, and responsiveness.

Investigation and Evaluation of the Transdermal Delivery of Ibuprofen in Various Characterized Nano-Drug Delivery Systems.

The aim was to assess the suitability of three nano-based transdermal drug delivery systems containing ibuprofen: a nano-emulsion, a nano-emulgel, and a colloidal suspension with ibuprofen-loaded nanoparticles. Understanding the transdermal delivery of ibuprofen using nano-based drug delivery systems can lead to more effective pain relief and improved patient compliance. Characterization tests assessed the suitability of the developed drug delivery systems. Membrane release and skin diffusion studies, along with tape stripping, were performed to determine drug release and skin permeation of ibuprofen. In vitro cytotoxicity studies on HaCaT cells were conducted using MTT and neutral red assays to evaluate the safety of the developed drug delivery systems. Characterization studies confirmed stable drug delivery systems with ideal properties for transdermal delivery. Membrane release studies demonstrated the successful release of ibuprofen. In vitro skin diffusion experiments and tape stripping, detecting ibuprofen in the receptor phase, stratum corneum-epidermis, and epidermis-dermis, indicating successful transdermal and topical delivery. The in vitro cytotoxicity studies observed only minor cytotoxic effects on HaCaT cells, indicating the safety of the developed drug delivery systems. The investigation demonstrated promising results for the transdermal delivery of ibuprofen using the developed drug delivery systems, which contributes to valuable insights that may lead to improved pain management strategies.

Biosensors as early warning detection systems for waterborne Cryptosporidium.

Waterborne disease is a global health threat contributing to a high burden of diarrhoeal disease, and growing evidence indicates a prospective increase in incidence coinciding with the profound effects of climate change. A major causative agent of gastrointestinal disease is Cryptosporidium, a protozoan waterborne parasite identified in over 70 countries. Cryptosporidium is a cause of high disease morbidity in children and the immunocompromised with limited treatment options for patients at risk of severe illness. The hardy nature of the organism leads to its persistence in various water sources, with certain water treatment procedures proving inefficient for its complete removal. While diagnostic methods for Cryptosporidium are well-defined in the clinical sphere, detection of Cryptosporidium in water sources remains suboptimal due to low dispersion of organisms in large sample volumes, lengthy processing times and high costs of equipment and reagents. A need for improvement exists to identify the organism as an emerging threat in domestic water systems, and the technological advantages that biosensors offer over current analytical methods may provide a preventative approach to outbreaks of Cryptosporidium. Biosensors are innovative, versatile and adaptable analytical tools that could provide highly sensitive, rapid, on-site analysis needed for Cryptosporidium detection in low-resource settings.

Situation analysis on the regulation of nanomedicines in Southern Africa.

Background: Medical products incorporating nanoparticle drug delivery systems (nanomedicines) are therapeutic or imaging agents, which comprise a delivery system within the nanometer size range (1 - 1000 nm). As medical products, nanomedicines meet definitions of medicines according to various national legislations for regulation of medicines. However, for the regulation of nanomedicines, additional assessments including toxicological issues have to be considered. These complexities require extra regulatory effort. In the resource-limited context of low- and middle-income countries, many National Medicines Regulatory Authorities (NMRAs) lack resources and capacities to effectively assure the quality of medicinal products in their countries. With emerging trends in innovative technologies, including nanotechnology, this burden is worsened. The need to overcome regulatory challenges drove the formation of a work sharing initiative in the Southern African Development Community (SADC), ZaZiBoNA in 2013. Regulatory agencies participating in this initiative cooperate in the assessment of applications for registration of medicines. Methods: A cross-sectional exploratory study design with qualitative techniques was used to investigate the status of the regulation of nanomedicines in Southern African countries in particular those participating in the ZaZiBoNA initiative. Results: The study found that in general, NMRAs are aware of the existence of nanomedicines and they apply legislation applicable to other medical products. The NMRAs however neither have specific definition for nanomedicines and technical guidance documents, nor technical committees specific for consideration of nanomedicines. Collaboration with external experts or organisations in the regulation of nanomedicines was also found to be lacking. Discussion: Capacity building and collaboration in the area of regulation of nanomedicines is strongly encouraged.

The domestication of the African Union model law on medical products regulation: Perceived benefits, enabling factors, and challenges.

Introduction: In 2016, the African Union (AU) Model Law on Medical Products Regulation was endorsed by AU Heads of State and Government. The aims of the legislation include harmonisation of regulatory systems, increasing collaboration across countries, and providing a conducive regulatory environment for medical product/health technology development and scale-up. A target was set to have at least 25 African countries domesticating the model law by 2020. However, this target has not yet been met. This research aimed to apply the Consolidated Framework for Implementation Research (CFIR) in analysing the rationale, perceived benefits, enabling factors, and challenges of AU Model Law domestication and implementation by AU Member States. Methods: This study was a qualitative, cross-sectional, census survey of the national medicines regulatory authorities (NRAs) of Anglophone and Francophone AU Member States. The heads of NRAs and a senior competent person were contacted to complete self-administered questionnaires. Results: The perceived benefits of model law implementation include enabling the establishment of an NRA, improving NRA governance and decision-making autonomy, strengthening the institutional framework, having streamlined activities which attract support from donors, as well as enabling harmonisation, reliance, and mutual recognition mechanisms. The factors enabling domestication and implementation are the presence of political will, leadership, and advocates, facilitators, or champions for the cause. Additionally, participation in regulatory harmonisation initiatives and the desire to have legal provisions at the national level that allow for regional harmonisation and international collaboration are enabling factors. The challenges encountered in the process of domesticating and implementing the model law are the lack of human and financial resources, competing priorities at the national level, overlapping roles of government institutions, and the process of amending/repealing laws being slow and lengthy. Conclusion: This study has enabled an improved understanding of the AU Model Law process, the perceived benefits of its domestication, and the enabling factors for its adoption from the perspective of African NRAs. NRAs have also highlighted the challenges encountered in the process. Addressing these challenges will result in a harmonised legal environment for medicines regulation in Africa and be an important enabler for the effective operation of the African Medicines Agency.

Comparative study on the topical and transdermal delivery of diclofenac incorporated in nano-emulsions, nano-emulgels, and a colloidal suspension.

Transdermal delivery of active pharmaceutical ingredients (APIs) can be challenging, since the skin possesses a rate-limiting barrier, which may be overcome when APIs possess certain ideal physicochemical properties. The lack thereof would require that APIs be included in drug delivery vehicles to enhance skin permeation. Hence, diclofenac was incorporated into various drug delivery vehicles (i.e., nano-emulsions, nano-emulgels, and a colloidal suspension containing drug-loaded nanoparticles) to investigate the transdermal delivery thereof, while nano-emulsions and nano-emulgels had varying concentrations of evening primrose oil (EPO). The aim of the study was to compare the topical and transdermal diclofenac delivery from the different types of vehicles and to investigate the influence the different EPO concentrations had on diclofenac delivery. After characterization, membrane release studies were performed (to determine whether the API was successfully released from the vehicle) followed by in vitro skin diffusion studies and tape stripping (to establish whether the vehicles assisted the API in reaching the target site (transdermal delivery)). Lastly, cytotoxicity studies were conducted via methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on human keratinocyte (HaCaT) cells. Results showed minimal cytotoxic effects at concentrations equivalent to that which had permeated through the skin, while the membrane release and in vitro skin diffusion studies indicated that the nano-emulsions and the 10% EPO vehicles increased API release and diffusion when compared to the other vehicles. However, the colloidal suspension had the highest concentrations of API within the skin. Hence, all the vehicles were non-toxic and effectively delivered diclofenac through the transdermal route.

Collaborative reliance in medicine safety and quality regulation: Investigation of experiences in handling N-nitrosamine impurities among ZaZiBoNa participating countries.

Introduction: The presence of N-nitrosamine impurities in medicines raised concerns globally as they are genotoxic and probable human carcinogens. A review of N-nitrosamine impurities in medicines provides an opportunity for National Regulatory Authorities (NRAs) to ensure that corrective and preventive actions are applied so that safe and good quality medicines are made available to the public. This study aimed to investigate the experiences on reviews conducted by NRAs from various Southern African Development Community countries which participate in the regional work-sharing forum, ZaZiBoNa, on the quality and safety data due to the presence of N-nitrosamine impurities in medicines. Methods: A comparative, descriptive study using mixed methods was conducted. Purposive sampling was applied in selecting research participants based on their participation status in the ZaZiBoNa initiative. A standardized questionnaire structured into five parts was completed by ZaZiBoNa focal persons/nominated individuals to determine the experience of each NRA in addressing the safety and quality issues related to the presence of N-nitrosamine impurities in the affected medicines. Profiled medicines included sartans, ranitidine, metformin, rifampicin, and rifapentine. Results: Sartan medicines had been reviewed by all countries participating in the ZaZiBoNa initiative. Although most NRAs have yet to conduct reviews on other profiled medicines, evaluations have been implemented to ensure access to safe and good quality medicines within the region. Most countries experienced challenges in communicating with applicants or marketing authorization holders (MAHs) on reviewing N-nitrosamine impurities in their medicines. The majority of NRAs agree that there is a need for further collaboration efforts to review N-nitrosamine impurities in medicines. Conclusion: The review of N-nitrosamine impurities in the profiled medicines by NRAs within the region has demonstrated the importance of enhanced regulatory oversight to safeguard against the risks associated with medicines. Collaborative reliance on the review of the safety and quality of medicine, continuous monitoring, implementation and review of processes, testing methods, and regular engagements with stakeholders could be essential in ensuring adequate control of N-nitrosamine impurities in medicines.

Cathelicidins and defensins antimicrobial host defense peptides in the treatment of TB and HIV: Pharmacogenomic and nanomedicine approaches towards improved therapeutic outcomes.

Tuberculosis (TB) and human immunodeficiency virus (HIV) represent a significant burden of disease on a global scale. Despite improvements in the global epidemic status, largely facilitated by increased access to pharmacotherapeutic interventions, slow progress in the development of new clinical interventions coupled with growing antimicrobial resistance to existing therapies represents a global health crisis. There is an urgent need to expand the armamentarium of TB and HIV therapeutic strategies. Host mediated immune responses represent an untapped reservoir of novel approaches for TB and HIV. Antimicrobial peptides (AMPs) are an essential aspect of the immune system. Cathelicidins and defensins AMPs have been studied for their potential applications in TB and HIV therapeutic interventions. Genetic polymorphism across different population groups may affect endogenous expression or activity of AMPs, potentially influencing therapeutic outcomes. However, certain genetic polymorphisms in autophagy pathways may alter the downstream effects of nano-delivery of cathelicidin. On the other hand, certain genetic polymorphisms in beta-defensins may provide a protective role in reducing HIV-1 mother-to-child-transmission. Pharmaceutical development of cathelicidins and defensins is disadvantaged with complex challenges. Nanoparticle formulations improve pharmacokinetics and biocompatibility while facilitating targeted drug delivery, potentially minimising the risk of immunogenicity or non-specific haemolytic activity. This review aims to explore the potential viability of using cathelicidins and defensins as novel pharmacotherapy in the management of TB and HIV, highlight potential pharmacogenomic implications in host mediated immunity and AMP therapeutic applications, as well as propose novel drug delivery strategies represented by nanomedicine for AMPs.

Medicines Regulatory Science Expertise in Africa: Workforce Capacity Development and Harmonisation Activities Towards the Establishment of the African Medicines Agency.

The medicines regulatory landscape in Africa is undergoing transformation with at least two countries having National Medicines Regulatory Authorities (NRAs) that operate at World Health Organization (WHO) maturity level 3. However, this represents the exception as over 90% of African NRAs have limited capacity to perform core medicine regulatory functions, have a shortage of competent regulatory professionals, have high staff turnover, lack diversity of scientific expertise, and have staffing shortages relative to the high workload. A systematic approach to developing the regulatory workforce is therefore crucial to addressing the existing shortfalls in regulatory capacity, particularly at this time when efforts are underway to operationalise the African Medicines Agency (AMA). In this article, initiatives that are building African NRAs' regulatory capacity and developing their workforce are reviewed in preparation for work to be conducted by the AMA. We found that the African Medicines Regulatory Harmonisation (AMRH) initiative has been at the forefront of capacity building and workforce development mainly through the designation of specialised Regional Centres of Regulatory Excellence and the implementation of medicines regulatory harmonisation initiatives in regional economic communities. In addition, some NRAs within high-income countries and trusted institutions have been supporting regulators in low-income countries with registration assessments and facilitating access to quality-assured medical products through their stringent review procedures (SRPs). Capacity building has subsequently been facilitated through this active involvement of African regulators in SRPs. This article also provides recommendations for further capacity building and workforce development.

A Perspective on Nanotechnology and COVID-19 Vaccine Research and Production in South Africa.

Advances in nanotechnology have enabled the development of a new generation of vaccines, which are playing a critical role in the global control of the COVID-19 pandemic and the return to normalcy. Vaccine development has been conducted, by and large, by countries in the global north. South Africa, as a major emerging economy, has made extensive investments in nanotechnology and bioinformatics and has the expertise and resources in vaccine development and manufacturing. This has been built at a national level through decades of investment. In this perspective article, we provide a synopsis of the investments made in nanotechnology and highlight how these could support innovation, research, and development for vaccines for this disease. We also discuss the application of bioinformatics tools to support rapid and cost-effective vaccine development and make recommendations for future research and development in this area to support future health challenges.

Permeation Challenges of Drugs for Treatment of Neurological Tuberculosis and HIV and the Application of Magneto-Electric Nanoparticle Drug Delivery Systems.

The anatomical structure of the brain at the blood-brain barrier (BBB) creates a limitation for the movement of drugs into the central nervous system (CNS). Drug delivery facilitated by magneto-electric nanoparticles (MENs) is a relatively new non-invasive approach for the delivery of drugs into the CNS. These nanoparticles (NPs) can create localized transient changes in the permeability of the cells of the BBB by inducing electroporation. MENs can be applied to deliver antiretrovirals and antibiotics towards the treatment of human immunodeficiency virus (HIV) and tuberculosis (TB) infections in the CNS. This review focuses on the drug permeation challenges and reviews the application of MENs for drug delivery for these diseases. We conclude that MENs are promising systems for effective CNS drug delivery and treatment for these diseases, however, further pre-clinical and clinical studies are required to achieve translation of this approach to the clinic.

Recent Advances in the Development of Antimicrobial and Antifouling Biocompatible Materials for Dental Applications.

The risk of secondary bacterial infections resulting from dental procedures has driven the design of antimicrobial and antifouling dental materials to curb pathogenic microbial growth, biofilm formation and subsequent oral and dental diseases. Studies have investigated approaches based primarily on contact-killing or release-killing materials. These materials are designed for addition into dental resins, adhesives and fillings or as immobilized coatings on tooth surfaces, titanium implants and dental prosthetics. This review discusses the recent developments in the different classes of biomaterials for antimicrobial and antifouling dental applications: polymeric drug-releasing materials, polymeric and metallic nanoparticles, polymeric biocides and antimicrobial peptides. With modifications to improve cytotoxicity and mechanical properties, contact-killing and anti-adhesion materials show potential for incorporation into dental materials for long-term clinical use as opposed to short-lived antimicrobial release-based coatings. However, extended durations of biocompatibility testing, and adjustment of essential biomaterial features to enhance material longevity in the oral cavity require further investigations to confirm suitability and safety of these materials in the clinical setting. The continuous exposure of dental restorative and regenerative materials to pathogenic microbes necessitates the implementation of antimicrobial and antifouling materials to either replace antibiotics or improve its rational use, especially in the day and age of the ever-increasing problem of antimicrobial resistance.

Establishment of the African Medicines Agency: progress, challenges and regulatory readiness.

Insufficient access to quality, safe, efficacious and affordable medical products in Africa has posed a significant challenge to public health for decades. In part, this is attributed to weak or absent policies and regulatory systems, a lack of competent regulatory professionals in National Medicines Regulatory Authorities (NMRAs) and ineffective regional collaborations among NMRAs. In response to national regulatory challenges in Africa, a number of regional harmonisation efforts were introduced through the African Medicines Regulatory Harmonisation (AMRH) initiative to, among others, expedite market authorisation of medical products and to facilitate the alignment of national legislative frameworks with the AU Model Law on Medical Products Regulation. The goals of the model law include to increase collaboration across countries and to facilitate the overall regional harmonisation process. The AMRH initiative is proposed to serve as the foundation for the establishment of the African Medicines Agency (AMA). The AMA will, as one of its mandates, coordinate the regional harmonisation systems that are enabled by AU Model Law domestication and implementation. In this paper, we review the key entities involved in regional and continental harmonisation of medicines regulation, the milestones achieved in establishing the AMA as well as the implementation targets and anticipated challenges related to the AU Model Law domestication and the AMA's establishment. This review shows that implementation targets for the AU Model Law have not been fully met, and the AMA treaty has not been ratified by the minimum required number of countries for its establishment. In spite of the challenges, the AU Model Law and the AMA hold promise to address gaps and inconsistencies in national regulatory legislation as well as to ensure effective medicines regulation by galvanising technical support, regulatory expertise and resources at a continental level. Furthermore, this review provides recommendations for future research.

Curdlan-Chitosan Electrospun Fibers as Potential Scaffolds for Bone Regeneration.

Polysaccharides have received a lot of attention in biomedical research for their high potential as scaffolds owing to their unique biological properties. Fibrillar scaffolds made of chitosan demonstrated high promise in tissue engineering, especially for skin. As far as bone regeneration is concerned, curdlan (1,3-ß-glucan) is particularly interesting as it enhances bone growth by helping mesenchymal stem cell adhesion, by favoring their differentiation into osteoblasts and by limiting the osteoclastic activity. Therefore, we aim to combine both chitosan and curdlan polysaccharides in a new scaffold for bone regeneration. For that purpose, curdlan was electrospun as a blend with chitosan into a fibrillar scaffold. We show that this novel scaffold is biodegradable (8% at two weeks), exhibits a good swelling behavior (350%) and is non-cytotoxic in vitro. In addition, the benefit of incorporating curdlan in the scaffold was demonstrated in a scratch assay that evidences the ability of curdlan to express its immunomodulatory properties by enhancing cell migration. Thus, these innovative electrospun curdlan-chitosan scaffolds show great potential for bone tissue engineering.