Antibiotic-loaded hydroxyapatite scaffolds fabricated from Nile tilapia bones for orthopaedics.

This work aimed to develop new antibiotic-coated/ antibiotic-loaded hydroxyapatite (HAp) scaffolds for orthopaedic trauma, specifically to treat the infection after fixation of skeletal fracture. The HAp scaffolds were fabricated from the Nile tilapia (Oreochromis niloticus) bones and fully characterized. The HAp scaffolds were coated with 12 formulations of poly (lactic-co-glycolic acid) (PLGA) or poly (lactic acid) (PLA), blended with vancomycin. The vancomycin release, surface morphology, antibacterial properties, and the cytocompatibility of the scaffolds were conducted. The HAp powder contains elements identical to those found in human bones. This HAp powder is suitable as a starting material to build scaffolds. After the scaffold fabrication, The ratio of HAp to ß-TCP changed, and the phase transformation of ß-TCP to α-TCP was observed. All antibiotic-coated/ antibiotic-loaded HAp scaffolds can release vancomycin into the phosphate-buffered saline (PBS) solution. PLGA-coated scaffolds obtained faster drug release profiles than PLA-coated scaffolds. The low polymer concentration in the coating solutions (20%w/v) gave a faster drug release profile than the high polymer concentration (40%w/v). All groups showed a trace of surface erosion after being submerged in PBS for 14 days. Most of the extracts can inhibit Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA). The extracts not only caused no cytotoxicity to Saos-2 bone cells but also can increase cell growth. This study demonstrates that it is possible to use these antibiotic-coated/ antibiotic-loaded scaffolds in the clinic as an antibiotic bead replacement.

Electrospun PVB/AVE NMs as mask filter layer for win-win effects of filtration and antibacterial activity.

The COVID-19 pandemic has caused serious social and public health problems. In the field of personal protection, the facial masks can prevent infectious respiratory diseases, safeguard human health, and promote public safety. Herein, we focused on preparing a core filter layer for masks using electrospun polyvinyl butyral/apocynum venetum extract nanofibrous membranes (PVB/AVE NMs), with durable interception efficiency and antibacterial properties. In the spinning solution, AVE acted as a salt to improve electrical conductivity, and achieve long-lasting interception efficiency with adjustable pore size. It also played the role of an antibacterial agent in PVB/AVE NMs to achieve win-win effects. The hydrophobicity of PVB-AVE-6% was 120.9° whereas its filterability reached 98.3% when the pressure drop resistance was 142 Pa. PVB-AVE-6% exhibited intriguing properties with great antibacterial rates of 99.38% and 98.96% against S. aureus and E. coli, respectively. After a prolonged usability test of 8 h, the filtration efficiency of the PVB/AVE masks remained stable at over 97.7%. Furthermore, the antibacterial rates of the PVB/AVE masks on S. aureus and E. coli were 96.87% and 96.20% respectively, after using for 2 d. These results indicate that PVB/AVE NMs improve the protective performance of ordinary disposable masks, which has certain application in air filtration.

Extracellular vesicle-loaded hydrogels for tissue repair and regeneration.

Extracellular vesicles (EVs) are a collective term for nanoscale or microscale vesicles secreted by cells that play important biological roles. Mesenchymal stem cells are a class of cells with the potential for self-healing and multidirectional differentiation. In recent years, numerous studies have shown that EVs, especially those secreted by mesenchymal stem cells, can promote the repair and regeneration of various tissues and, thus, have significant potential in regenerative medicine. However, due to the rapid clearance capacity of the circulatory system, EVs are barely able to act persistently at specific sites for repair of target tissues. Hydrogels have good biocompatibility and loose and porous structural properties that allow them to serve as EV carriers, thereby prolonging the retention in certain specific areas and slowing the release of EVs. When EVs are needed to function at specific sites, the EV-loaded hydrogels can stand as an excellent approach. In this review, we first introduce the sources, roles, and extraction and characterization methods of EVs and describe their current application status. We then review the different types of hydrogels and discuss factors influencing their abilities to carry and release EVs. We summarize several strategies for loading EVs into hydrogels and characterizing EV-loaded hydrogels. Furthermore, we discuss application strategies for EV-loaded hydrogels and review their specific applications in tissue regeneration and repair. This article concludes with a summary of the current state of research on EV-loaded hydrogels and an outlook on future research directions, which we hope will provide promising ideas for researchers.

Skin cancer biology and barriers to treatment: Recent applications of polymeric micro/nanostructures.

Background: Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease. Aim of review: Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies. Key scientific concepts of review: In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

The balanced microenvironment regulated by the degradants of appropriate PLGA scaffolds and chitosan conduit promotes peripheral nerve regeneration.

Tissue-engineered nerve grafts (TENGs) are the most promising way for repairing long-distance peripheral nerve defects. Chitosan and poly (lactic-co-glycolic acid) (PLGA) scaffolds are considered as the promising materials in the pharmaceutical and biomedical fields especially in the field of tissue engineering. To further clarify the effects of a chitosan conduit inserted with various quantity of poly (lactic-co-glycolic acid) (PLGA) scaffolds, and their degrades on the peripheral nerve regeneration, the chitosan nerve conduit inserted with different amounts of PLGA scaffolds were used to repair rat sciatic nerve defects. The peripheral nerve regeneration at the different time points was dynamically and comprehensively evaluated. Moreover, the influence of different amounts of PLGA scaffolds on the regeneration microenvironment including inflammatory response and cell state were also revealed. The modest abundance of PLGA is more instrumental to the success of nerve regeneration, which is demonstrated in terms of the structure of the regenerated nerve, reinnervation of the target muscle, nerve impulse conduction, and overall function. The PLGA scaffolds aid the migration and maturation of Schwann cells. Furthermore, the PLGA and chitosan degradation products in a correct ratio neutralize, reducing the inflammatory response and enhancing the regeneration microenvironment. The balanced microenvironment regulated by the degradants of appropriate PLGA scaffolds and chitosan conduit promotes peripheral nerve regeneration. The findings represent a further step towards programming TENGs construction, applying polyester materials in regenerative medicine, and understanding the neural regeneration microenvironment.

Delivery strategies of amphotericin B for invasive fungal infections.

Invasive fungal infections (IFIs) represent a growing public concern for clinicians to manage in many medical settings, with substantial associated morbidities and mortalities. Among many current therapeutic options for the treatment of IFIs, amphotericin B (AmB) is the most frequently used drug. AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance. In this review, we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs. We have also discussed the mechanism of actions of AmB, rationale for treating IFIs, and recent advances in formulating AmB for clinical use. Finally, this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.

A novel experimental approach to evaluate guided bone regeneration (GBR) in the rat femur using a 3D-printed CAD/CAM zirconia space-maintaining barrier.

INTRODUCTION: Obtaining a certain bone volume is an important goal in implantology or orthopedics. Thus, after tooth extraction, quite a lot of horizontal and vertical alveolar bone is lost in time and can be detrimental to the implant treatment outcome, while the treatment of critical bone defects is a considerable challenge for surgery. OBJECTIVES: In this study we designed a new in vivo model as an useful experimental tool to assess guided bone regeneration (GBR) using a computer-aided design/manufacturing (CAD-CAM) space-maintaining barrier. METHODS: The barrier was 3D printed with three progressive heights, surgically placed on rat femur, and GBR results were analyzed at 2, 4, and 8 weeks by X-ray and bone mineral density analysis, histology/morphometry and by immunofluorescence and immunohistochemistry for osteogenesis and angiogenesis evaluation. RESULTS: The obtained results show that the proposed experimental model provides a real-time useful information on progressive bone tissue formation, which depends on the volume of isolated space created for GBR and on molecular events that lead to satisfactory vertical and horizontal bone augmentation and osteointegration. CONCLUSION: In conclusion, the proposed customized three-dome space-maintaining barrier is suitable as an experimental tool to assess the potential of using the designed barriers in dentistry and orthopedics to promote the formation of new bone and determine their space- and time-dependent limitations. Meanwhile, guided bone augmentation for dentistry requires subsequent evaluation on an alveolar bone preclinical model followed by clinical implementation.

Recent developments in biomaterials for long-bone segmental defect reconstruction: A narrative overview.

Reconstruction of long-bone segmental defects (LBSDs) has been one of the biggest challenges in orthopaedics. Biomaterials for the reconstruction are required to be strong, osteoinductive, osteoconductive, and allowing for fast angiogenesis, without causing any immune rejection or disease transmission. There are four main types of biomaterials including autograft, allograft, artificial material, and tissue-engineered bone. Remarkable progress has been made in LBSD reconstruction biomaterials in the last ten years. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our aim is to summarize recent developments in the divided four biomaterials utilized in the LBSD reconstruction to provide the clinicians with new information and comprehension from the biomaterial point of view.

Biotinylated HPMA centered polymeric nanoparticles for Bortezomib delivery.

Bortezomib (BTZ) is a proteasome inhibitor as approved by US FDA for the treatment of multiple myeloma. It exhibits significant anti-cancer properties, against solid tumors; but lacks aqueous solubility, chemical stability which hinders its successful formulation development. The present study is an attempt to deliver BTZ using N-(2-hydroxypropyl) methacrylamide (HPMA) based copolymeric conjugates and biotinylated PNPs in an effective manner. Study describes a systematic synthetic pathway to synthesize functional polymeric conjugates such as HPMA-Biotin (HP-BT) HPMA-Polylactic acid (HPLA) and HPMA-PLA-Biotin (HPLA-BT) followed by exhaustive characterization both spectroscopically and microscopically. Our strategy yielded polymeric nanoparticles (PNPs) of narrow size range of 199.7 ± 1.32 nm. Release studies were performed at pH 7.4 and 5.6. PNPs were 2-folds less hemolytic (p < 0.0001) than pure drug. BTZ loaded PNPs of HPLA-BT demonstrated significant anti-cancer activity against MCF-7 cells. IC50 value of these PNPs was 56.06 ± 0.12 nM, which was approximately two folds less than BTZ (p < 0.0001). Cellular uptake study confirmed that higher uptake of formulations might be an outcome of biotin surface tethering characteristics that enhanced selectivity and targeting of formulations efficiently. In vivo pharmacokinetics evidenced increased bioavailability (AUC0 t-∞) of DL-HPLA-BT PNPs (drug loaded) than BTZ with an improved half-life. Overall the developed PNPs led to the improved and effective BTZ delivery.

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles.

Nanoparticles are considered to be a powerful approach for the delivery of poorly water-soluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation (FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles, polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer (CIJM), multi-inlet vortex mixer (MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly water-soluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.

Design and fabrication of porous biodegradable scaffolds: a strategy for tissue engineering.

Current strategies of tissue engineering are focused on the reconstruction and regeneration of damaged or deformed tissues by grafting of cells with scaffolds and biomolecules. Recently, much interest is given to scaffolds which are based on mimic the extracellular matrix that have induced the formation of new tissues. To return functionality of the organ, the presence of a scaffold is essential as a matrix for cell colonization, migration, growth, differentiation and extracellular matrix deposition, until the tissues are totally restored or regenerated. A wide variety of approaches has been developed either in scaffold materials and production procedures or cell sources and cultivation techniques to regenerate the tissues/organs in tissue engineering applications. This study has been conducted to present an overview of the different scaffold fabrication techniques such as solvent casting and particulate leaching, electrospinning, emulsion freeze-drying, thermally induced phase separation, melt molding and rapid prototyping with their properties, limitations, theoretical principles and their prospective in tailoring appropriate micro-nanostructures for tissue regeneration applications. This review also includes discussion on recent works done in the field of tissue engineering.

Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles.

Oral drug absorption is a process influenced by the physicochemical and biopharmaceutical properties of the drug and its inter-relationship with the gastrointestinal tract. Drug solubility, dissolution and permeability across intestinal barrier are the key parameters controlling absorption. This review provides an overview of the factors that affect drug absorption and the classification of a drug on the basis of solubility and permeability. The biopharmaceutical classification system (BCS) was introduced in early 90׳s and is a regulatory tool used to predict bioavailability problems associated with a new entity, thereby helping in the development of a drug product. Strategies to combat solubility and permeability issues are also discussed.