3D printed drug loaded nanomaterials for wound healing applications.

Wounds are a stern healthcare concern in the growth of chronic disease conditions as they can increase healthcare costs and complicate internal and external health. Advancements in the current and newer management systems for wound healing should be in place to counter the health burden of wounds. Researchers discovered that two-dimensional (2D) media lacks appropriate real-life detection of cellular matter as these have highly complicated and diverse structures, compositions, and interactions. Hence, innovation towards three-dimensional (3D) media is called to conquer the high-level assessment and characterization in vivo using new technologies. The application of modern wound dressings prepared from a degenerated natural tissue, biodegradable biopolymer, synthetic polymer, or a composite of these materials in wound healing is currently an area of innovation in tissue regeneration medicine. Moreover, the integration of 3D printing and nanomaterial science is a promising approach with the potential for individualized, flexible, and precise technology for wound care approaches. This review encompasses the outcomes of various investigations on recent advances in 3D-printed drug-loaded natural, synthetic, and composite nanomaterials for wound healing. The challenges associated with their fabrication, clinical application progress, and future perspectives are also addressed.

Surface Disinfection Practice in Public Hospitals in the Era of COVID-19: Assessment of Disinfectant Solution Preparation and Use in Addis Ababa, Ethiopia.

Background: Surface disinfection of healthcare facilities with appropriate disinfectants is among the infection control strategies against the spread of coronavirus disease 2019 (COVID-19). As sodium hypochlorite solution (SHS) is a commonly used surface disinfectant, its preparation and proper use should be given a due attention. The current study aimed at assessing the practice of Addis Ababa public hospitals in the preparation and use of SHS. Methods: A cross-sectional observational study was employed to assess the adequacy of disinfectant solution preparation and use. Checklists were used for data collection. Descriptive statistics were used for data analyses, and categorical variables were described by frequencies and percentages. Results: Out of the twelve public hospitals included in the study; only three hospitals checked the potency of the working SHS. Majority of the hospitals (8 hospitals) stored the concentrated SHS products in cool, dry, and direct sunlight protected places. It was only in one hospital where appropriate personal protective equipment was used during the preparation and quality control activities. Surfaces were not cleaned in all hospitals before disinfection; and the rooms were ventilated only in 2 hospitals during the application of the disinfectant solution. Conclusion: The study revealed that the preparations of SHS in the public hospitals did not comply with most of the requirements of good compounding practice. Moreover, standard practices were not maintained in majority hospitals during the use of SHS for surface disinfection. As a control strategy in the spread of COVID-19 and other infections, appropriate corrective actions shall be implemented in the studied hospitals to mitigate the limitations observed in the preparation and use of SHS.

Evaluation of quality and antimicrobial efficacy of locally manufactured alcohol-based hand sanitizers marketed in Addis Ababa, Ethiopia in the era of COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been rapidly spreading across the globe since the World Health Organization (WHO) has declared the disease outbreak as a global pandemic on March 11, 2020. Hand hygiene, via either regular handwashing with soap and water or using hand sanitizers, is among the various measures that need to be followed to control the outbreak of the disease. Alcohol-based hand sanitizers (ABHS) are the "gold standard" for hand disinfection because of their broad antimicrobial spectrum of activity, easy availability, better safety profile, and general acceptability to users. This study aimed at evaluating the physicochemical quality and antimicrobial efficacy of the locally manufactured ABHS marketed in Addis Ababa, Ethiopia. METHODS: A cross-sectional survey was used to collect ABHS from Addis Ababa marketplaces. A total of 25 sample products were randomly selected from different categories of hand sanitizer manufacturers. The physicochemical evaluation of the products was carried out as per the United States Pharmacopoeia and WHO standards. Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella spp., and Shigella spp clinical isolates were used for the antimicrobial efficacy test. RESULTS: The Fourier Transform Infrared result confirmed that all the test products met the identification test for ethanol. The majority (68%) of ABHS complied with the test for ethanol content (75-85% v/v). However, only 3 products fulfilled the hydrogen peroxide content (0.112-0.137% v/v). LPC307 showed the maximum zone of inhibition of 12 mm against Escherichia coli whereas MPC204 exhibited only 3 mm. LPC101 was found to be more sensitive to Shigella and Klebsiella Spp with minimum inhibitory concentration values of 20% and 10%, respectively. The sample product LPC101 showed a minimum bactericidal concentration of 20% against Escherichia coli, Pseudomonas aeruginosa, and Klebsiella spp. CONCLUSION: One-third of the tested ABHS did not comply with the WHO ethanol content limit and the majority of the products failed to meet the label claim for hydrogen peroxide content. Besides, nearly all products proved that they have activity against all the tested pathogenic microorganisms at a minimum concentration from 10 to 80%; though, they did not show 99.9% bacteriostatic or bactericidal activities as claimed. The study findings suggested regular monitoring of the quality of marketed ABHS considering the current wide use of these products.

The contribution of nano-based strategies in overcoming ceftriaxone resistance: a literature review.

Antimicrobial drug resistance, including resistance to multiple antibiotics, is continuously increasing. According to research findings, many bacteria resistant to other antibiotics were susceptible to ceftriaxone. However, over the last few years, ceftriaxone resistance has become growing and extremely worrisome challenge to the global healthcare system and several strategies have been initiated to contain the spread of antimicrobial drug resistance. Its extended use for therapeutic or preventative measures in humans and farm animals resulted in the development and spread of resistance. Recent advances in nanotechnology also offer novel formulations based on distinct types of nanostructure particles with different sizes and shapes, and flexible antimicrobial properties. For ceftriaxone, several nanostructured formulations through conjugation, intercalation, encapsulation with lipid carrier, and polymeric films have been investigated by different groups with promising results in combating the development of resistance. This review addressed the existing knowledge and practice on the contribution of nano-based delivery approaches in overcoming ceftriaxone resistance. Evidences have been generated from published research articles using major search electronic databases such as PubMed, Medline, Google Scholar, and Science Direct.

Three dimensional printed nanostructure biomaterials for bone tissue engineering.

The suffering from organ dysfunction due to damaged or diseased tissue/bone has been globally on the rise. Current treatment strategies for non-union bone defects include: the use of autografts, allografts, synthetic grafts and free vascularized fibular grafts. Bone tissue engineering has emerged as an alternative for fracture repair to satisfy the current unmet need of bone grafts and to alleviate the problems associated with autografts and allografts. The technology offers the possibility to induce new functional bone regeneration using synergistic combination of functional biomaterials (scaffolds), cells, and growth factors. Bone scaffolds are typically made of porous biodegradable materials that provide the mechanical support during repair and regeneration of damaged or diseased bone. Significant progress has been made towards scaffold materials for structural support, desired osteogenesis and angiogenesis abilities. Thanks for innovative scaffolds fabrication technologies, bioresorbable scaffolds with controlled porosity and tailored properties are possible today. Despite the presence of different bone scaffold fabrication methods, pore size, shape and interconnectivity have not yet been fully controlled in most of the methods. Moreover, scaffolds with tailored porosity for specific defects are still difficult to manufacture. Nevertheless, such scaffolds can be designed and fabricated using three dimensional (3D) printing approaches. 3D printing technology, as an advanced tissue scaffold fabrication method, offers the opportunity to produce complex geometries with distinct advantages. The technology has been used for the production of various types of bodily constructs such as blood vessels, vascular networks, bones, cartilages, exoskeletons, eyeglasses, cell cultures, tissues, organs and novel drug delivery devices. This review focuses on 3D printed scaffolds and their application in bone repair and regeneration. In addition, different classes of biomaterials commonly employed for the fabrication of 3D nano scaffolds for bone tissue engineering application so far are briefly discussed.

Poly-l-lactic acid scaffold incorporated chitosan-coated mesoporous silica nanoparticles as pH-sensitive composite for enhanced osteogenic differentiation of human adipose tissue stem cells by dexamethasone delivery.

Nowadays, the development of drug-loaded electrospun organic-inorganic composite scaffolds for tissue engineering application is an attractive approach. In this study, a composite scaffold of Poly-l-lactic acid (PLLA) incorporated dexamethasone (Dexa) loaded Mesoporous Silica Nanoparticles (MSN) coated with Chitosan (CS) were fabricated by electrospinning for bone tissue engineering application. The MSN was prepared by precipitation method. After that, Dexamethasone (Dexa) was loaded into MSNs (MSN-Dexa). In the following, CS was coated over the prepared nanoparticles to form MSN-Dexa@CS and then, were mixed to PLLA solution to form MSN-Dexa@CS/PLLA composite for electrospinning. The surface morphology, hydrophilicity, tensile strength and the bioactivity of the scaffolds were characterized. The osteogenic proliferation and differentiation potential were evaluated by MTT assay and by measuring the basic osteogenic markers: the activity of the enzyme alkaline phosphatase and the level of calcium deposition. The composite scaffolds prepared here have conductive surface property and have a better osteogenic potential than pure PLLA scaffolds. Hence, the controlled release of nanoparticle containing Dexa from composite scaffold supported the osteogenesis and made the composite scaffolds ideal candidates for bone tissue engineering application and pH-sensitive delivery of drugs at the site of implantation in tissue regeneration.

Enhanced osteogenic differentiation of mesenchymal stem cells on metal-organic framework based on copper, zinc, and imidazole coated poly-l-lactic acid nanofiber scaffolds.

The presence of inorganic bioactive minerals with polymers can accelerate and promote several processes including: bone cell joining, proliferation, differentiation, and expression of osteogenic proteins. In this study, zinc (Zn), copper (Cu), and imidazole metal-organic framework (MOF) nanoparticles were synthesized and coated over poly-l-lactic acid (PLLA) nanofibrous scaffolds for bone tissue engineering application. The surface and bioactive features of the scaffolds were characterized. The osteogenic potential of the scaffolds on human adipose tissue-derived mesenchymal stem cells (MSCs) was evaluated. Zn-Cu imidazole MOF coated PLLA scaffolds (PLLA@MOF) showed a comparable rate of MSC proliferation with the pure PLLA scaffolds and tissue culture plate (TCP). However, the PLLA@MOF potential of osteogenic differentiation was significantly greater than either pristine PLLA scaffolds or TCP. Hence, coating Zn-Cu imidazole MOF has a significant effect on the osteogenesis of MSC. Therefore, PLLA@MOF is novel scaffolds with bioactive components which are crucial for osteoconductivity and also able to provoke the osteogenesis and angiogenesis.

Dexamethasone loaded multi-layer poly-l-lactic acid/pluronic P123 composite electrospun nanofiber scaffolds for bone tissue engineering and drug delivery.

In tissue engineering, it is common to mix drugs that can control proliferation and differentiation of cells into polymeric solutions as part of composite to get bioactive scaffolds. However, direct incorporation of drugs might potentially result in undesired burst release. To overcome this problem, here we developed electrospun multilayer drug loaded poly-l-lactic acid/pluronic P123 (PLLA-P123) composite scaffolds. The drug was loaded into the middle layer. The surface, the mechanical and physiochemical properties of the scaffolds were evaluated. The drug release profiles were monitored. Finally, the osteogenic proliferation and differentiation potential were determined. The scaffolds fabricated here have appropriate surface properties, but with different mechanical strength and osteogenic proliferation and differentiation. Multi-layer scaffolds where the drug was in the middle layer and PLLA-plasma and PLLA-P123 with cover layer showed the best osteogenic proliferation and differentiation than the other groups of scaffolds. The drug release profiles of the scaffolds were completely different: single layer scaffolds showed burst release within the first day, while multilayer scaffolds showed controlled release. Therefore, the multilayer drug loaded scaffolds prepared have dual benefits can provide both better osteogenesis and controlled release of drugs and bioactive molecules at the implant site.

An improved surface for enhanced stem cell proliferation and osteogenic differentiation using electrospun composite PLLA/P123 scaffold.

Poly-L-lactic acid (PLLA) nano fibrous scaffolds prepared by electrospinning technology have been used widely in tissue engineering applications. However, PLLA scaffolds are hydrophobic in nature, moreover the fibrous porous structure produced by electrospinning makes the scaffolds even more hydrophobic which generally limits cell attachment and proliferation. Polymer blending is one of the several efforts used so far to enhance hydrophilicity and recognized as an easy cost-effective approach for the manipulation physiochemical properties of polymeric biomaterials. Pluronic block copolymers containing hydrophilic poly(ethylene oxide) (PEO) blocks and hydrophobic poly(propylene oxide) (PPO) blocks are arranged in triblock structure: PEO-PPO-PEO. It is commonly used recently to blend hydrophobic polymers to enhance hydrophilicity for pharmaceutical and tissue engineering applications. In this study, novel pluronic P123 blend PLLA electrospun nanofibre scaffolds with improved hydrophilicity and biological properties were fabricated. The surface morphology and surface chemistry of the nanofibre scaffolds were characterized by scanning electron microscope (SEM) and FTIR analyses. Surface hydrophilicity and change in mechanical properties were studied. The ability of the scaffolds to support the attachment, and proliferation and differentiation of human adipose tissue derived MSCs, were evaluated generally. The fabricated scaffolds have completely improved, hydrophilicity, similar osteogenic differentiation potential with plasma-treated PLLA nanofibre scaffold, and hence P123 blend PLLA electrospun nanofibre scaffolds are a very good and cost effective choice as a scaffold for bone tissue engineering application.

Osteogenic differentiation of mesenchymal stem cells cultured on PLLA scaffold coated with Wharton's Jelly.

Poly-L-lactic acid (PLLA) electrospun nanofiber scaffold is one of the most commonly used synthetic polymer scaffolds for bone tissue engineering application. However, PLLA is hydrophobic in nature, hence does not maintain proper cell adhesion and tissue formation, moreover, it cannot provide the osteo-inductive environment due to inappropriate surface characteristic and the lack of surface motives participating in the first cellular events. To modify these shortcomings different approaches have been used, among those the most commonly used one is coating of the surface of the electrospun nanofiber with natural materials. In this work Wharton's jelly (WJ), a tissue which surrounds the umbilical cord vessels, reaches in high amounts of extracellular matrix (ECM) components mainly; collagen, hyaluronic acid and several sulphated glycosaminoglycans (GAGs) were used to cover the surface of electrospun PLLA nanofiber scaffolds. The surface morphology of the nanofiber scaffold was evaluated via scanning electron microscope, and the in vitro osteogenic differentiation potential was determined by MTT assay and common osteogenic marker tests such as alkaline phosphatase (ALP) activity and calcium deposition tests. Coating of WJ could not change the surface morphology and diameter of the nanofibers. However, WJ-PLLA scaffolds showed higher proliferation of human mesenchymal stem cells (MSC) than tissue culture plate (TCP) and pristine PLLA scaffolds, moreover, WJ-PPLA scaffold demonstrated significant alkaline phosphatase activity and calcium mineralization than either TCP or PLLA nanofiber scaffolds.

Nanotechnology for delivery of gemcitabine to treat pancreatic cancer.

Pancreatic cancer (PC) is one of the most deadly and quickly fatal human cancers with a 5-year mortality rate close to 100%. Its prognosis is very poor, mainly because of its hostile biological behavior and late onset of symptoms for clinical diagnosis; these bring limitations on therapeutic interventions. Factors contributing for the difficulties in treating PC include: high rate of drug resistance, fast metastasis to different organs, poor prognosis and relapse of the tumor after therapy. After being approved by US FDA 1997, Gemcitabine (Gem) is the first line and the gold standard drug for all stages of advanced PC till now. However, its efficacy is unsatisfactory, mainly due to; its chemical instability and poor cellular uptake, resulting in an extremely short half-life and low bioavailability. To solve this drawbacks and increase the therapeutic outcome important progress has been achieved in the field of nanotechnology and offers a promising and effective alternative. This review mainly focus on the most commonly investigated nanoparticle (NP) delivery systems of Gem for PC treatment and the latest progresses achieved. Novel nanocarriers with better tumor targeting efficiencies and maximum treatment outcome to treat this deadly due are given much attention.