Harnessing Natural Polymers for Nano-Scaffolds in Bone Tissue Engineering: A Comprehensive Overview of Bone Disease Treatment.

Numerous surgeries are carried out to replace tissues that have been harmed by an illness or an accident. Due to various surgical interventions and the requirement of bone substitutes, the emerging field of bone tissue engineering attempts to repair damaged tissues with the help of scaffolds. These scaffolds act as template for bone regeneration by controlling the development of new cells. For the creation of functional tissues and organs, there are three elements of bone tissue engineering that play very crucial role: cells, signals and scaffolds. For the achievement of these aims, various types of natural polymers, like chitosan, chitin, cellulose, albumin and silk fibroin, have been used for the preparation of scaffolds. Scaffolds produced from natural polymers have many advantages: they are less immunogenic as well as being biodegradable, biocompatible, non-toxic and cost effective. The hierarchal structure of bone, from microscale to nanoscale, is mostly made up of organic and inorganic components like nanohydroxyapatite and collagen components. This review paper summarizes the knowledge and updates the information about the use of natural polymers for the preparation of scaffolds, with their application in recent research trends and development in the area of bone tissue engineering (BTE). The article extensively explores the related research to analyze the advancement of nanotechnology for the treatment of bone-related diseases and bone repair.

[Nanotechnologies in ophthalmology]. / Nanotekhnologii v oftal'mologii.

Application of new materials and methods in the diagnosis and treatment of eye diseases is one of the promising research areas in modern ophthalmology. Significant progress has been made in understanding the pathogenesis, diagnosis and treatment of eye diseases using nanotechnologies and nanomaterials. This paper presents the main achievements and results of original research on this issue. It has been shown that nanoparticles are able to overcome biological barriers, deliver drugs to the target site, and provide the required drug release rate. Modern nanotechnological approaches in tissue engineering are also being actively introduced into ophthalmology, making it possible to create nanoframeworks for growing three-dimensional cellular structures, including arrays of pigment epithelium cells and retinal ganglion cells for the treatment of retinal damage caused by degenerative diseases, injuries and infections.

DNA Origami Frameworks Enabled Self-Protective siRNA Delivery for Dual Enhancement of Chemo-Photothermal Combination Therapy.

Although chemotherapy and photothermal therapy are widely used to combat cancer, their efficacy is often limited by multidrug resistance. Small interfering RNAs (siRNAs) have ability to suppress the expression of target genes, which has been extensively employed for combating the multidrug resistance to chemodrugs and hyperthermia in cancer therapy. However, efficient delivery of siRNAs along with chemo-photothermal agents in vivo is still an enormous challenge. Herein, octahedral DNA origami frameworks (OctDOFs) are constructed as a nanovehicle for precise organization and orchestrated delivery of siRNAs, chemodrugs (doxorubicin, Dox), and photothermal agents (gold nanorods, AuNRs) in combinatorial treatment of cancer. The inner cavity of the rigid OctDOFs structure is able to shield the encapsulated siRNAs during transportation by sterically hindering RNase degradation and protein binding, thus achieving effective downregulation of connective tissue growth factor (CTGF) and heat shock protein 72 (HSP72) for dual sensitization of cancer cells to chemodrugs and hyperthermia. By amplifying chemo-photothermal therapeutic potency with siRNAs, the proposed OctDOFs exhibited superior cytotoxicity and tumor inhibition efficacy in vitro and in vivo. This nanovehicle creates a promising siRNA delivery platform for precise medication and combination therapy.

Preparation of PLA/chitosan nanoscaffolds containing cod liver oil and experimental diabetic wound healing in male rats study.

Diabetes mellitus is one of the most common metabolic disorders. One of the important metabolic complications in diabetes is diabetic foot ulcer syndrome, which causes delayed and abnormal healing of the wound. The formulation of nanoscaffolds containing cod liver oil by altering the hemodynamic balance toward the vasodilators state, increasing wound blood supply, and altering plasma membrane properties, namely altering the membrane phospholipids composition, can be effective in wound healing. In this study, electrospinning method was used to produce poly lactic acid/chitosan nanoscaffolds as a suitable bio-substitute. After preparing the nanoscaffolds, the products were characterized with dynamic light scattering (DLS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Also optical properties of polymer and comparison between adsorption between single polymer and polymer-drug calculated with UV-Vis spectra. The structure and functional groups of the final products were characterized by Fourier-transform infrared spectroscopy (FT-IR) and energy dispersive spectroscopy (EDAX) as elemental analysis. The results showed that the optimum formulation of cod liver oil was 30%, which formed a very thin fiber that rapidly absorbed to the wound and produced significant healing effects. According to the results, poly lactic acid/chitosan nanoscaffolds containing cod liver oil can be a suitable bio-product to be used in treating the diabetic foot ulcer syndrome.

Myogenic differentiation of primary myoblasts and mesenchymal stromal cells under serum-free conditions on PCL-collagen I-nanoscaffolds.

BACKGROUND: The creation of functional skeletal muscle via tissue engineering holds great promise without sacrificing healthy donor tissue. Different cell types have been investigated regarding their myogenic differentiation potential under the influence of various media supplemented with growth factors. Yet, most cell cultures include the use of animal sera, which raises safety concerns and might lead to variances in results. Electrospun nanoscaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining both biocompatibility and stability. We therefore aimed to develop a serum-free myogenic differentiation medium for the co-culture of primary myoblasts (Mb) and mesenchymal stromal cells derived from the bone marrow (BMSC) and adipose tissue (ADSC) on electrospun poly-ε-caprolacton (PCL)-collagen I-nanofibers. RESULTS: Rat Mb were co-cultured with rat BMSC (BMSC/Mb) or ADSC (ADSC/Mb) two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-nanofibers. Differentiation media contained either AIM V, AIM V and Ultroser® G, DMEM/Ham's F12 and Ultroser® G, or donor horse serum (DHS) as a conventional differentiation medium. In 2D co-culture groups, highest upregulation of myogenic markers could be induced by serum-free medium containing DMEM/Ham's F12 and Ultroser® G (group 3) after 7 days. Alpha actinin skeletal muscle 2 (ACTN2) was upregulated 3.3-fold for ADSC/Mb and 1.7-fold for BMSC/Mb after myogenic induction by group 3 serum-free medium when compared to stimulation with DHS. Myogenin (MYOG) was upregulated 5.2-fold in ADSC/Mb and 2.1-fold in BMSC/Mb. On PCL-collagen I-nanoscaffolds, ADSC showed a higher cell viability compared to BMSC in co-culture with Mb. Myosin heavy chain 2, ACTN2, and MYOG as late myogenic markers, showed higher gene expression after long term stimulation with DHS compared to serum-free stimulation, especially in BMSC/Mb co-cultures. Immunocytochemical staining with myosin heavy chain verified the presence of a contractile apparatus under both serum free and standard differentiation conditions. CONCLUSIONS: In this study, we were able to myogenically differentiate mesenchymal stromal cells with myoblasts on PCL-collagen I-nanoscaffolds in a serum-free medium. Our results show that this setting can be used for skeletal muscle tissue engineering, applicable to future clinical applications since no xenogenous substances were used.

A unique perylene-based DNA intercalator: localization in cell nuclei and inhibition of cancer cells and tumors.

To date, perylene derivatives have not been explored as DNA intercalator to inhibit cancer cells by intercalating into the base pairs of DNA. Herein, a water-soluble perylene bisimide (PBDI) that efficiently intercalates into the base pairs of DNA is synthesized. Excitingly, PBDI is superior to the commercial DNA intercalator, amonafide, for specific nuclear accumulation and effective suppression of cancer cells and tumors.

The emerging role of nanoscaffolds in chronic diabetic wound healing: a new horizon for advanced therapeutics.

Non-healing or chronic wounds in extremities that lead to amputations in patients with Type II diabetes (hyperglycemia) are among the most serious and common health problems in the modern world. Over the past decade, more efficient solutions for diabetic ulcers have been developed. Nanofibers and/or composite materials capable of drug delivery, moisture control, and antibacterial effectiveness are increasingly utilized in the formulation of wound dressings, with a particular focus on the biofunctionalization of polymeric and hydrogel materials. Natural products, including plant extracts, honey, antibacterial agents, nanozymes, and metal nanoparticles, are now commonly and effectively implemented to enhance the functionality of wound dressings. Due to the complicated and dysfunctional physiological structure of the chronic wound sites in the extremities of diabetic patients, formulated nanoscaffold or hydrogel components are becoming more intricate and versatile. This study aimed to investigate the development of wound dressing materials over the years while demonstrating their progressively enhanced complexity in effectively targeting, treating, and managing chronic wounds. The mechanisms of action and bio-functionality of wound dressing technologies were elucidated based on findings from 290 studies conducted over the last decade. A notable observation that emerged from these studies is the evolution of wound dressing development technology, which has led to significant advancements in the operational range of smart systems. These include, but are not limited to, self-healing, self-oxygenation, and adaptable mimicry of human tissue.

3D printed biopolymer/black phosphorus nanoscaffolds for bone implants: A review.

Bone implantation is one of the recognized and effective means of treating bone defects, but osteoporosis and bone tumor-related bone abnormalities have a series of problems such as susceptibility to infection, difficulty in healing, and poor therapeutic effect, which poses a great challenge to clinical medicine. Three-dimensional things may be printed using 3D printing. Researchers can feed materials through the printer layer by layer to create the desired shape for a 3D structure. It is widely employed in the healing of bone defects, and it is an improved form of additive manufacturing technology with prospective future applications. This review's objective is to provide an overview of the findings reports pertaining to 3D printing biopolymers in recent years, provide an overview of biopolymer materials and their composites with black phosphorus for 3D printing bone implants, and the characterization methods of composite materials are also summarized. In addition, summarizes 3D printing methods based on ink printing and laser printing, pointing out their special features and advantages, and provide a combination strategy of photothermal therapy and bone regeneration materials for black phosphorus-based materials. Finally, the associations between bone implant materials and immune cells, the bio-environment, as well as the 3D printing bone implants prospects are outlined.

PLGA nanomedical consignation: A novel approach for the management of prostate cancer.

The malignancy of the prostate is a complicated ailment which impacts millions of male populations around the globe. Despite the multitude of endeavour accomplished within this domain, modalities that are involved in the ameliorative management of predisposed infirmity are still relent upon non-specific and invasive procedures, thus imposing a detrimental mark on the living standard of the individual. Also, the orchestrated therapeutic interventions are still incompetent in substantiating a robust and unabridged therapeutic end point owing to their inadequate solubility, low bioavailability, limited cell assimilation, and swift deterioration, thereby muffling the clinical application of these existing treatment modalities. Nanotechnology has been employed in an array of modalities for the medical management of malignancies. Among the assortment of available nano-scaffolds, nanocarriers composed of a bio-decomposable and hybrid polymeric material like PLGA hold an opportunity to advance as standard chemotherapeutic modalities. PLGA-based nanocarriers have the prospect to address the drawbacks associated with conventional cancer interventions, owing to their versatility, durability, nontoxic nature, and their ability to facilitate prolonged drug release. This review intends to describe the plethora of evidence-based studies performed to validate the applicability of PLGA nanosystem in the amelioration of prostate malignancies, in conjunction with PLGA focused nano-scaffold in the clinical management of prostate carcinoma. This review seeks to explore numerous evidence-based studies confirming the applicability of PLGA nanosystems in ameliorating prostate malignancies. It also delves into the role of PLGA-focused nano-scaffolds in the clinical management of prostate carcinoma, aiming to provide a comprehensive perspective on these advancements.

Effect of chitin-architected spatiotemporal three-dimensional culture microenvironments on human umbilical cord-derived mesenchymal stem cells.

Mesenchymal stem cell (MSC) transplantation has been explored for the clinical treatment of various diseases. However, the current two-dimensional (2D) culture method lacks a natural spatial microenvironment in vitro. This limitation restricts the stable establishment and adaptive maintenance of MSC stemness. Using natural polymers with biocompatibility for constructing stereoscopic MSC microenvironments may have significant application potential. This study used chitin-based nanoscaffolds to establish a novel MSC three-dimensional (3D) culture. We compared 2D and 3D cultured human umbilical cord-derived MSCs (UCMSCs), including differentiation assays, cell markers, proliferation, and angiogenesis. When UCMSCs are in 3D culture, they can differentiate into bone, cartilage, and fat. In 3D culture condition, cell proliferation is enhanced, accompanied by an elevation in the secretion of paracrine factors, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) by UCMSCs. Additionally, a 3D culture environment promotes angiogenesis and duct formation with HUVECs (Human Umbilical Vein Endothelial Cells), showing greater luminal area, total length, and branching points of tubule formation than a 2D culture. MSCs cultured in a 3D environment exhibit enhanced undifferentiated, as well as higher cell activity, making them a promising candidate for regenerative medicine and therapeutic applications.

Nanotechnology for Pain Management.

Introduction: In the context of the current opioid crisis, non-pharmacologic approaches to pain management have been considered important alternatives to the use of opioids or analgesics. Advancements in nano and quantum technology have led to the development of several nanotransporters, including nanoparticles, micelles, quantum dots, liposomes, nanofibers, and nano-scaffolds. These modes of nanotransporters have led to the development of new drug formulations. In pain medicine, new liposome formulations led to the development of DepoFoam™ introduced by Pacira Pharmaceutical, Inc. (Parsippany, NJ, USA). This formulation is the base of DepoDur™, which comprises a combination of liposomes and extended-release morphine, and Exparel™, which comprises a combination of liposomes and extended-release bupivacaine. In 2021, Heron Therapeutics (San Diego, CA, USA) created Zynrelef™, a mixture of bupivacaine and meloxicam. Advancements in nanotechnology have led to the development of devices/patches containing millions of nanocapacitors. Data suggest that these nanotechnology-based devices/patches reduce acute and chronic pain. Methods: Google and PubMed searches were conducted to identify studies, case reports, and reviews of medical nanotechnology applications with a special focus on acute and chronic pain. This search was based on the use of keywords like nanotechnology, nano and quantum technology, nanoparticles, micelles, quantum dots, liposomes, nanofibers, nano-scaffolds, acute and chronic pain, and analgesics. This review focuses on the role of nanotechnology in acute and chronic pain. Results: (1) Nanotechnology-based transporters. DepoDur™, administered epidurally in 15, 20, or 25 mg single doses, has been demonstrated to produce significant analgesia lasting up to 48 h. Exparel™ is infiltrated at the surgical site at the recommended dose of 106 mg for bunionectomy, 266 mg for hemorrhoidectomy, 133 mg for shoulder surgery, and 266 mg for total knee arthroplasty (TKA). Exparel™ is also approved for peripheral nerve blocks, including interscalene, sciatic at the popliteal fossa, and adductor canal blocks. The injection of Exparel™ is usually preceded by an injection of plain bupivacaine to initiate analgesia before bupivacaine is released in enough quantity from the depofoarm to be pharmacodynamically effective. Finally, Zynrelef™ is applied at the surgical site during closure. It was initially approved for open inguinal hernia, abdominal surgery requiring a small-to-medium incision, foot surgery, and TKA. (2) Nanotechnology-based devices/patches. Two studies support the use of nanocapacitor-based devices/patches for the management of acute and chronic pain. A randomized study conducted on patients undergoing unilateral primary total knee (TKA) and total hip arthroplasty (THA) provided insight into the potential value of nanocapacitor-based technology for the control of postoperative acute pain. The results were based on 2 studies, one observational and one randomized. The observational study was conducted in 128 patients experiencing chronic pain for at least one year. This study suggested that compared to baseline, the application of a nanocapacitor-based Kailo™ pain relief patch on the pain site for 30 days led to a time-dependent decrease in pain and analgesic use and an increase in well-being. The randomized study compared the effects of standard of care treatment to those of the same standard of care approach plus the use of two nanocapacitor-based device/patches (NeuroCuple™ device) placed in the recovery room and kept in place for three days. The study demonstrated that the use of the two NeuroCuple™ devices was associated with a 41% reduction in pain at rest and a 52% decrease in the number of opioid refills requested by patients over the first 30 days after discharge from the hospital. Discussion: For the management of pain, the use of nano-based technology has led to the development of nano transporters, especially focus on the use of liposome and nanocapacitors. The use of liposome led to the development of DepoDur™, bupivacaine Exparel™ and a mixture of bupivacaine and meloxicam (Zynrelef™) and more recently lidocaine liposome formulation. In these cases, the technology is used to prolong the duration of action of drugs included in the preparation. Another indication of nanotechnology is the development of nanocapacitor device or patches. Although, data obtained with the use of nanocapacitors are still limited, evidence suggests that the use of nanocapacitors devices/patches may be interesting for the treatment of both acute and chronic pain, since the studies conducted with the NeuroCuple™ device and the based Kailo™ pain relief patch were not placebo-controlled, it is clear that additional placebo studies are required to confirm these preliminary results. Therefore, the development of a placebo devices/patches is necessary. Conclusions: Increasing evidence supports the concept that nanotechnology may represent a valuable tool as a drug transporter including liposomes and as a nanocapacitor-based device/patch to reduce or even eliminate the use of opioids in surgical patients. However, more studies are required to confirm this concept, especially with the use of nanotechnology incorporated in devices/patches.

Bioactive stem cell-laden 3D nanofibrous scaffolds for tissue engineering.

This study presents biomimetic nanoscaffolds composed of electrospun polycaprolactone-collagen (PCL-Coll) nanofibers, loaded with bioactive Arnebia euchroma (AE) extract and stem cells, to develop cell-based tissue engineering constructs. The incorporation of AE extract, known for its antioxidant and anti-inflammatory properties, into the PCL-Coll nanofibers resulted in nanoscaffolds denoted as PCL-Coll/AE0, PCL-Coll/AE5, PCL-Coll/AE10, and PCL-Coll/AE15, corresponding to AE extract concentrations of 0.0, 5.0, 10.0, and 15.0 wt%, respectively. The PCL-Coll/AE nanoscaffolds exhibited high porosity values of 62.81 ± 4.78 %, 59.9 ± 2.10 %, 52.44 ± 2.66 %, and 46.32 ± 1.35 %, respectively, thereby providing an optimal 3D environment for cell attachment and proliferation. Analysis of the AE extract revealed the presence of abundant shikonin, a key bioactive compound, as indicated by its characteristic absorption bands at 490, 520, and 560 nm. FE-SEM data confirmed the homogeneous immobilization of AE compounds within the 3D nanofiber scaffolds, with fibers averaging 316 ± 137 nm in diameter, falling within the range of natural collagen fibers. To evaluate the structural integrity of the fully stem cell-laden scaffolds, we assessed cell growth, cell attachment within the PCL-Coll/AE nanoscaffolds, the cytoprotective effects of AE extract, and the expression levels of stemness-related genes, including Nanog, Rex1, Sox2, Oct4, Klf4, and C-Myc. Real-time PCR assays indicated that key indicators of stemness were upregulated, with average increases from 120 ± 15 % in PCL-Coll/AE0 to 250 ± 30 % in PCL-Coll/AE15 over a two-week period. These upregulations promote cell proliferation and facilitate cell cycle progression. Data indicate that increasing the concentration of bioactive AE extract within the scaffolds enhanced cell adhesion on the scaffold surface and improved cell viability after 7 days of culture, with viability rising from 109 ± 6.15 % in PCL-Coll/AE0 to 145.5 ± 10.11 % in PCL-Coll/AE15. Cytoprotective assays against oxidative stress induced by H2O2 revealed relative cell viability for PCL-Coll/AE0, PCL-Coll/AE5, PCL-Coll/AE10, and PCL-Coll/AE15 as 42.78 ± 5.85 %, 49.29 ± 6.79 %, 64.98 ± 3.32 %, and 78.68 ± 3.09 %, respectively. These results correlate with the antioxidant potency of AE extract compounds, particularly shikonin and its derivatives. Therefore, the cell-laden biomimetic PCL-Coll/AE15 scaffolds, which demonstrate sustained stemness features and a continuous local release of bioactive AE compounds, represent a promising candidate for tissue engineering applications.

A review on background, process and application of electrospun nanofibers for tissue regeneration.

Electrospinning is a versatile method which is used to synthesize nano/micro sized fibers under the influence of an electric field. Electrospun nanoscaffolds are one of the widely accepted platforms for cultivating soft and hard tissues as they create a perfect micro-environment for cell adhesion, proliferation and differentiation. Nanoscaffolds are widely used in the field of tissue engineering due to their versatility in aiding the growth of different types of cells and tissues for varied applications. The composition, molecular weight and structure of polymer used to fabricate nanoscaffold plays an important role in determining the size and strength of the nanofibers prepared. This review gives information about the background, process and different types of polymers used in electrospinning. Recent advances in culturing liver cells, osteoblasts, skin cells, neural cells and coronary artery smooth muscle cells on nanoscaffolds are also elucidated.

Effective Modulation of Inflammation and Oxidative Stress for Enhanced Regeneration of Intervertebral Discs Using 3D Porous Hybrid Protein Nanoscaffold.

Degeneration of fibrocartilaginous tissues is often associated with complex pro-inflammatory factors. These include reactive oxygen species (ROS), cell-free nucleic acids (cf-NAs), and epigenetic changes in immune cells. To effectively control this complex inflammatory signaling, it developed an all-in-one nanoscaffold-based 3D porous hybrid protein (3D-PHP) self-therapeutic strategy for treating intervertebral disc (IVD) degeneration. The 3D-PHP nanoscaffold is synthesized by introducing a novel nanomaterial-templated protein assembly (NTPA) strategy. 3D-PHP nanoscaffolds that avoid covalent modification of proteins demonstrate inflammatory stimuli-responsive drug release, disc-mimetic stiffness, and excellent biodegradability. Enzyme-like 2D nanosheets incorporated into nanoscaffolds further enabled robust scavenging of ROS and cf-NAs, reducing inflammation and enhancing the survival of disc cells under inflammatory stress in vitro. Implantation of 3D-PHP nanoscaffolds loaded with bromodomain extraterminal inhibitor (BETi) into a rat nucleotomy disc injury model effectively suppressed inflammation in vivo, thus promoting restoration of the extracellular matrix (ECM). The resulting regeneration of disc tissue facilitated long-term pain reduction. Therefore, self-therapeutic and epigenetic modulator-encapsulated hybrid protein nanoscaffold shows great promise as a novel approach to restore dysregulated inflammatory signaling and treat degenerative fibrocartilaginous diseases, including disc injuries, providing hope and relief to patients worldwide.

Taming Multiscale Structural Complexity in Porous Skeletons: From Open Framework Materials to Micro/Nanoscaffold Architectures.

Recent developments in the design and synthesis of more and more sophisticated organic building blocks with controlled structures and physical properties, combined with the emergence of novel assembly modes and nanofabrication methods, make it possible to tailor unprecedented structurally complex porous systems with precise multiscale control over their architectures and functions. By tuning their porosity from the nanoscale to microscale, a wide range of functional materials can be assembled, including open frameworks and micro/nanoscaffold architectures. During the last two decades, significant progress is made on the generation and optimization of advanced porous systems, resulting in high-performance multifunctional scaffold materials and novel device configurations. In this perspective, a critical analysis is provided of the most effective methods for imparting controlled physical and chemical properties to multifunctional porous skeletons. The future research directions that underscore the role of skeleton structures with varying physical dimensions, from molecular-level open frameworks (<10 nm) to supramolecular scaffolds (10-100 nm) and micro/nano scaffolds (>100 nm), are discussed. The limitations, challenges, and opportunities for potential applications of these multifunctional and multidimensional material systems are also evaluated in particular by addressing the greatest challenges that the society has to face.

Label-free immunosensing of telomerase using bio-conjugation of biotinylated antibody to poly(chitosan) gold nanoparticles.

Aim: This study aimed to establish a label-free electrochemical biosensor for telomerase detection in human biofluid. Method: Synthesized green nanocomposite (poly[chitosan] decorated by gold nanoparticles) was used for the efficient immobilization of biotinylated antibody of telomerase and immunocomplex of antigen-antibody. Poly(chitosan) was decorated by gold nanoparticles on the surface of a glassy carbon electrode using an electrochemical coating technique. Results: The constructed immunosensor exhibited wide dynamic range (0.078-160 IU/ml-1) with a low limit of quantification of 0.078 IU/ml-1, which present a unique manner for telomerase assays in early prognosis for cancers. Conclusion: This study encourages scientists and scholars to design and develop new biosensor platforms for point-of-care diagnostics for telomerase management, an interesting reference for future research.

Development of a Nanohybrid Peptide Hydrogel for Enhanced Intervertebral Disc Repair and Regeneration.

Effective therapeutic approaches to overcome the heterogeneous pro-inflammatory and inhibitory extracellular matrix (ECM) microenvironment are urgently needed to achieve robust structural and functional repair of severely wounded fibrocartilaginous tissues. Herein we developed a dynamic and multifunctional nanohybrid peptide hydrogel (NHPH) through hierarchical self-assembly of peptide amphiphile modified with biodegradable two-dimensional nanomaterials with enzyme-like functions. NHPH is not only injectable, biocompatible, and biodegradable but also therapeutic by catalyzing the scavenging of pro-inflammatory reactive oxygen species and promoting ECM remodeling. In addition, our NHPH method facilitated the structural and functional recovery of the intervertebral disc (IVD) after severe injuries by delivering pro-regenerative cytokines in a sustained manner, effectively suppressing immune responses and eventually restoring the regenerative microenvironment of the ECM. In parallel, the NHPH-enhanced nucleus pulposus cell differentiation and pain reduction in a rat nucleotomy model further validated the therapeutic potential of NHPH. Collectively, our advanced nanoscaffold technology will provide an alternative approach for the effective treatment of IVD degeneration as well as other fibrocartilaginous tissue injuries.

Myogenic differentiation of human myoblasts and Mesenchymal stromal cells under GDF11 on NPoly-ɛ-caprolactone-collagen I-Polyethylene-nanofibers.

BACKGROUND: For the purpose of skeletal muscle engineering, primary myoblasts (Mb) and adipogenic mesenchymal stem cells (ADSC) can be co-cultured and myogenically differentiated. Electrospun composite nanofiber scaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining both biocompatibility and stability Although growth differentiation factor 11 (GDF11) has been proposed as a rejuvenating circulating factor, restoring skeletal muscle function in aging mice, some studies have also described a harming effect of GDF11. Therefore, the aim of the study was to analyze the effect of GDF11 on co-cultures of Mb and ADSC on poly-ε-caprolactone (PCL)-collagen I-polyethylene oxide (PEO)-nanofibers. RESULTS: Human Mb were co-cultured with ADSC two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-PEO-nanofibers. Differentiation media were either serum-free with or without GDF11, or serum containing as in a conventional differentiation medium. Cell viability was higher after conventional myogenic differentiation compared to serum-free and serum-free + GDF11 differentiation as was creatine kinase activity. Immunofluorescence staining showed myosine heavy chain expression in all groups after 28 days of differentiation without any clear evidence of more or less pronounced expression in either group. Gene expression of myosine heavy chain (MYH2) increased after serum-free + GDF11 stimulation compared to serum-free stimulation alone. CONCLUSIONS: This is the first study analyzing the effect of GDF11 on myogenic differentiation of Mb and ADSC co-cultures under serum-free conditions. The results of this study show that PCL-collagen I-PEO-nanofibers represent a suitable matrix for 3D myogenic differentiation of Mb and ADSC. In this context, GDF11 seems to promote myogenic differentiation of Mb and ADSC co-cultures compared to serum-free differentiation without any evidence of a harming effect.

Design, fabrication, optimization and characterization of memantine-loaded biodegradable PLGA nanoscaffolds for treatment of Alzheimer's disease.

This study aimed to design and develop nanoscaffolds for the controlled release of memantine by non-solvent-induced phase separation (N-TIPS) method. The development and optimization of nanoscaffolds was performed by Box-Behnken Design in which two independent formulation variables and one independent process variable: poly(lactic-co-glycolic acid) (PLGA) (X1), Pluronics F-127 (X2), and rotation speed (X3) were used. The design provided 15 formulation designs which were prepared to determine the response: percentage porosity (Y1) and drug loading (Y2). Polynomial equations were generated and analyzed statistically to establish a relationship between independent and dependent variables and develop an optimal formulation with maximized porosity (%) and drug loading (%). The optimized formulation batch was prepared using 19.18% w/v PLGA, 4.98% w/v Pluronics at 500 rpm rotation speed and exhibited drug loading of 11.66% and porosity of 82.62%. Further, correlation between the independent and dependent variables were established and statistically analyzed by using model generated mathematical regression equations, ANOVA, residual plots, interaction plot, main effect plot, contour plot and response surface designs. The analysis of model showed the significant individual effect of PLGA and significant interactive effect of Pluronics F-127 and rotation speed on drug loading and porosity. Further, its physicochemical characterization, andin-vitro(drug release kinetics, and PAMPA study),ex-vivo(enzyme inhibition assay and pro-inflammatory cytokines study) andin-vivo(neurobehavioral and histological study) studies were performed to evaluate the potential of memantine-loaded nanoscaffolds in the treatment of Alzheimer's disease (AD).

Functionalized Nanoparticles: A Paradigm Shift in Regenerative Endodontic Procedures.

Clinical treatment of inflamed tooth pulp mostly involves the removal of the entire pulp tissue. Because the vitality of the tooth is important for its ability to function, optimal regenerative biomaterials must be developed to maintain the vitality. Despite vast advances in the field of endodontics, the clinical translation of regenerative endodontic procedures and materials remains challenging. Patient-specific, tissue-derived stem cells play a major role in regeneration and revascularization, and these stem cells require an infection-free environment for a successful outcome. However, the high doses of antibiotics currently used to maintain an infection-free environment for tissue regeneration can be toxic for the stem cells. The introduction of nanotechnology in the field of regenerative procedures has overcome these issues and demonstrated promising results. Nanoparticles can be used to deliver antibiotics at very low doses owing to their small size, thereby enhancing antimicrobial activity and reducing the cytotoxic effect. Additionally, nanofibrous scaffolds provide an environment that is favorable for stem-cell migration and proliferation, thereby favoring the regeneration of the pulp-dentin complex. Nanotechnology can be used in the construction of nanofibrous scaffolds incorporated with different bioactive nanoparticles for favorable clinical outcomes. Nonetheless, the role of nanotechnology and the controlled release of various bioactive nanomolecules enhancing stem cell proliferation and regeneration of true pulp-dentin complex remains poorly understood. Given the importance of nanotechnology in tissue regeneration, this review provides an overview of the potential applications of nanotechnology in tooth pulp-dentin regeneration.