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Addressing the challenge of poor wound healing in chronic wounds remains complex, as the underlying physiological mechanisms are still not fully understood. Traditional wound dressings often fail to meet the specific needs of the chronic wound healing process. Recently, considerable interest has shifted toward employing biomacromolecule-based smart wound dressings to facilitate wound healing. These stimuli-responsive dressings have undergone substantial development to manage local drug delivery, demonstrating promising therapeutic effects in treating chronic wound defects. They have displayed improved drug release profiles both in vitro and in vivo. Recently, there have been advancements in the development of innovative dual and multi-stimuli responsive dressings that react to combinations of signals including pH-temperature, pH-enzyme, pH-ROS, pH-glucose, pH-NIR, and multiple stimuli. This paper offers an in-depth review of recent progress in responsive wound dressings based on biomacromolecules, with a specific focus on their design, drug release capabilities, and therapeutic advantages. [ABSTRACT FROM AUTHOR]

Addressing the challenge of poor wound healing in chronic wounds remains complex, as the underlying physiological mechanisms are still not fully understood. Traditional wound dressings often fail to meet the specific needs of the chronic wound healing process. Recently, considerable interest has shifted toward employing biomacromolecule-based smart wound dressings to facilitate wound healing. These stimuli-responsive dressings have undergone substantial development to manage local drug delivery, demonstrating promising therapeutic effects in treating chronic wound defects. They have displayed improved drug release profiles both in vitro and in vivo. Recently, there have been advancements in the development of innovative dual and multi-stimuli responsive dressings that react to combinations of signals including pH-temperature, pH-enzyme, pH-ROS, pH-glucose, pH-NIR, and multiple stimuli. This paper offers an in-depth review of recent progress in responsive wound dressings based on biomacromolecules, with a specific focus on their design, drug release capabilities, and therapeutic advantages. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has the worst prognosis among all breast cancer subtypes. The lack of proper treatments prompted scientists to find a practical targeted therapy to treat this type of tumor. Based on previous studies, tyrosine kinase-like orphan receptor (ROR1) is overexpressed in TNBC cells. Here, we designed a system consisting of superparamagnetic iron oxide nanoparticles (SPIONs) decorated with silk sericin (SS NPs) for the targeted delivery of ROR1 siRNA, a gene silencer to knockdown the expression of human ROR1 gene. NPs exhibited spherical shape of about 193 nm with acceptable properties both in vitro and in vivo. The apoptosis study showed significant death of MDA-MB-231 cells after 24 h treatment with the prepared NPs. The real-time PCR study also demonstrated an almost complete shutdown of ROR1 expression. Guided by magnetic field, enhanced accumulation of NPs was observed in breast tumors induced by 4T1 cells in BALB/c mice. Histological evaluation of the tumor exhibited necrosis 14 days post-treatment with the siRNA-loaded NPs; whereas, the untreated tumor was proliferating. Also, the tumor growth rate was significantly decreased after treatment with siRNA-loaded NPs in vivo. In conclusion, the prepared delivery system could be considered as a potential therapeutic strategy for treating TNBC. • Silk Sericin/SPION nanoparticles could efficiently deliver siRNA to the target site. • ROR1 siRNA-loaded SSP NPs effectively downregulated ROR1 gene expression. • Downregulation of the ROR1 gene significantly inhibited triple-negative breast cancer cells' progression. • The delivery system exhibited acceptable performance for the treatment and diagnosis of triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Thermosensitive nanoparticles with phase transition abilities have been considered as suitable materials in biomedical fields, especially drug delivery systems. Moreover, electroactive injectable hydrogels supporting bone regeneration of the elderly will highly be desired in bone tissue engineering applications. Herein, thermosensitive nanoparticles were fabricated using chitosan/poly(N-isopropyl acrylamide) for simvastatin acid delivery. The nanoparticles were incorporated into electroactive injectable hydrogels based on aniline pentamer/silk fibroin/polyacrylamide containing vitamin C. The nanoparticles had thermosensitive properties as simvastatin acid had higher release rates at 37 than 23 °C without significant burst release. The hydrogels also revealed an appropriate gelation time, stable mechanical and rheological characteristics, high water absorbency, and proper biodegradability. In vitro studies indicated that the hydrogel was biocompatible and nontoxic, especially those containing drugs. Implantation of the hydrogels containing both simvastatin acid and vitamin C into the critical calvarial bone defect of the aged rat also demonstrated significant enhancement of bone healing after 4 and 8 weeks post-implantation. We found that the electroactive injectable hydrogels containing thermosensitive nanoparticles exhibited great potential for treating bone defects in the elderly rats [ABSTRACT FROM AUTHOR]

• Hydrogel play a crucial role in wound healing by creating moist environment. • Quaternized chitosan hydrogel hold promises for environmentally sustainable. • Quaternized chitosan hydrogel has the potential for localized drug delivery. • Quaternized chitosan hydrogel play a significant role in wound healing. Hydrogel-based biomaterials applied as wound dressings provide the wound with a moist environment, which facilitates tissue regeneration through granulation and re-epithelialization. The inherent flexibility and adjustable architecture of hydrogels enables incorporation of cells, antimicrobial drugs, growth factors, and bioactive compounds, which leads to expediting wound contraction and enhancing the regeneration process. The utilization of natural polysaccharides, particularly chitosan, as a green and one of the most sustainable biomaterials among renewable resources, has been widely practised in wound healing because of its promising cost-effectiveness, biocompatibility, and biodegradability. However, the challenge of limited solubility of chitosan at neutral or basic media (pH ≥ 6.5) has been pinpointed. The exploration of quaternary chitosan hydrogels was a big step to combat its low solubility through the contribution of a quaternary ammonium group that improves the hydrophilicity and additionally brings about antibacterial activity over a wide range of pH. This review summarizes the latest progress in using hydrogel dressings based on quaternized chitosan for wound regeneration, encompassing various aspects such as hemostasis, antibacterial activity, antioxidant properties, and overall wound healing efficacy. Furthermore, the present review addresses the existing challenges and proposes possible solutions to enlarge development avenues in pursue of optimizing wound regeneration performance of quaternized chitosan-based hydrogels in prospect. [ABSTRACT FROM AUTHOR]

Electrospinning is well thought of as the most potent nanofiber producing technique, which is applicable in biomedical fields. The generation of electrospun nanofibers as drug carriers has widely been shown much interest over the past years. Electrospun nanofibers meet various advantages as drug delivery platforms including high surface area, acceptable mechanical properties based on the choice of the polymer, high processability, and the possibilities for surface modifications. Silk fibroin protein has gained a great attention as a drug delivery carrier due to ease of purification, sterilization, processability without using chemical crosslinkers, good biocompatibility, tailorable biodegradability, low immunogenicity, and high capacity to stabilize the loaded drugs. These characteristics along with advantageous benefits of electrospinning provide opportunities for producing suitable nanofibers based on silk fibroin for drug delivery purposes. It is also possible to incorporate various functional moieties to the electrospun silk fibroin nanofibers to enhance its biological activities. This review covers the progress in electrospinning of silk fibroin as a drug carrier in recent years. Unlabelled Image • Delivering the drug at the local area represents many advantages such as fine-tuning of the drug release rate at the site of disease. • Electrospun nanofibers are potential drug delivery carriers due to extraordinary structural and physico-chemical properties • The mild aqueous processes for loading sensitive biomolecules are of the benefits of using silk fibroin for drug delivery. • Amines, phenol, alcohol, thiol, and carboxyl groups in the backbone of silk fibroin facilitate the interaction with differentbiomolecules. • Electrospinning enables the fabrication of silk nanofibers with tailorable diameter and thickness to control the release kinetics of the drugs. [ABSTRACT FROM AUTHOR]

Nanocarriers sensitive to near infrared light (NIR) are useful templates for chemo-photothermal therapy (PTT) and imaging of tumors due to the ability to change the absorbed NIR energy to heat. The conventional photo-absorbing reagents lack the efficient loading and release of drug before reaching the target site leading to insufficient therapeutic outcomes. To overcome these limitations, the surface of nanocarriers can be modified with different polymers with wide functionalities to provide systems with diagnostic, therapeutic, and theranostic capabilities. Among various polymers, polydopamine (PDA) has been more interested due to complex structure with various chemical moieties, and the capacity to be used through different coating mechanism. In this review, we describe the complex structure, chemical properties, and coating mechanisms of PDA. Moreover, the advantage and surface modification of some relevant nanosystems based on carbon materials, gold, iron oxide, manganese, and upconverting nanomaterials by using PDA will be discussed, in detail. Unlabelled Image [ABSTRACT FROM AUTHOR]

Regenerating chondral and osteochondral injuries is a main challenge in orthopedics. Some therapeutic strategies such as joint preservation operations, non-operative management, palliative surgery, and arthroplasty are the common clinical methods for repairing the cartilage defects. These treatments show often satisfactory as short-term outcomes and without clear long-term prospects. Over the past decade, the development of tissue engineering technologies offers a new therapeutic option to treat patients suffering from chondral lesions. Silk fibroin is a potent and advanced biomaterial for regenerating both soft and hard tissues. Fibroin scaffolds possess superior mechanical strength, suitable bioactivity, elasticity, degradability, and tailorable chemical structure. Due to the important properties as natural biomaterials, the fabrications of various types of scaffolds/matrices for regenerating the tissues like cartilage for regeneration and repairing the defects are possible. This review highlights the investigations on silk-based biomaterials for cartilage tissue engineering. The possibilities for future clinical application of silk fibroin based constructs in repairing intervertebral disk, anterior cruciate ligament, meniscus, and osteochondral defects are evaluated in detail. [ABSTRACT FROM AUTHOR]

Abstract Lung cancer is the foremost reason of death from cancers with broad genetic and epigenetic diversity. Various strategies are clinically available for diagnosis and treatment of lung cancer. However, in many cases, the disease is diagnosed after malignancy that reduce the survival rate of lung cancer patients due to unsuccessful response to therapy. With the help of nanotechnology, various nanoparticulate systems including organic, inorganic, metallic, and polymeric nanoparticles have been developed for diagnosis and treatment of lung cancer. Each of these nanocarriers possess their own advantages and disadvantages. Combining the organic and inorganic components in a single hybrid nanosystem prepares a new generation of multifunctional nanoparticles with enhanced structural and biological properties. Such nanoparticles not only have beneficial features of all the bulk materials, but also can be tuned in terms of structural and functional moieties to provide carriers with improved diagnostic and therapeutic outcomes. Indeed, hybrid nanoparticles with the ability to incorporate multiple drugs, targeting agents, and photosensitive reagents opened new insights into developing more sensitive and specified systems for diagnosis and treatment of lung cancer compared with conventional nanocarriers. In this review, recent developments in designing different hybrid nanoparticles with diagnostic, therapeutic, and theranostic properties for lung cancer are explained in detail. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Silk fibroin (SF) is a natural fibrous polymer with strong potential for many biomedical applications. SF has attracted interest in the field of bone tissue engineering due to its extraordinary characteristics in terms of elasticity, flexibility, biocompatibility and biodegradability. However, low osteogenic capacity has limited applications for SF in the orthopedic arena unless suitably functionalized. Hydroxyapatite (HAp) is a well-established bioceramic with biocompatibility and appropriate for constructing orthopedic and dental substitutes. However, HAp ceramics tend to be brittle which can restrict applications in the repair of load-bearing tissues such as bones. Therefore, blending SF and HAp combines the useful properties of both materials as bone constructs for tissue engineering, the subject of this review. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries face some clinical obstacles and unsatisfactory functional outcomes. The slow regeneration rate of defected nerve delays functional recovery. To date, various therapeutic agents are used to enhance the survival and regeneration capacity of damaged neurons. Among these, nerve guide conduits held promise for peripheral nerve regeneration, through the physical guidance of the injured nerve across the lesions. Many natural and synthetic polymers are used to produce nerve conduits. Biopolymer-based biomaterials offer important options in control of structure, morphology, and chemistry as reasonable substitutes or mimics of extracellular matrix systems. Silk protein fibroin as a biocompatible natural polymer, possesses biodegradability, tunable mechanical properties, process ability, and suitable for the peripheral nerve conduits. This review highlights recent advances in the use of silk-based conduits for peripheral nerve regeneration. Further, the development of nerve conduits based on other biopolymers, including chitosan, alginate, collagen, and gelatin is discussed and compared. [ABSTRACT FROM PUBLISHER]

Small interfering RNA (siRNA) has established its reputation in the field of tissue engineering owing to its ability to silence the proteins that inhibit tissue regeneration. siRNA is capable of regulating cellular behavior during tissue regeneration processes. The concept of using siRNA technology in regenerative medicine derived from its ability to inhibit the expression of target genes involved in defective tissues and the possibility to induce the expression of tissue-inductive factors that improve the tissue regeneration process. To date, siRNA has been used as a suppressive biomolecule in different tissues, such as nervous tissue, bone, cartilage, heart, kidney, and liver. Moreover, various delivery systems have been applied in order to deliver siRNA to the target tissues. This review will provide an in-depth discussion on the development of siRNA and their delivery systems and mechanisms of action in different tissues. [ABSTRACT FROM AUTHOR]

Burn injuries are a major global problem, with a high risk of infection and mortality. This study aimed to develop an injectable hydrogel for wound dressings, composed of sodium carboxymethylcellulose/polyacrylamide/polydopamine containing vitamin C (CMC/PAAm/PDA VitC) for its antioxidant and antibacterial properties. Simultaneously, silk fibroin/alginate nanoparticles (SF/SANPs) loaded with curcumin (SF/SANPs CUR) were incorporated into the hydrogel to enhance wound regeneration and reduce bacterial infection. The hydrogels were fully characterized and tested in vitro and in preclinical rat models for biocompatibility, drug release, and wound healing efficacy. Results showed stable rheological properties, appropriate swelling and degradation ratios, gelation time, porosity, and free radical scavenging capacity. Biocompatibility was confirmed through MTT, lactate dehydrogenase, and apoptosis evaluations. Hydrogels containing curcumin demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In the preclinical study, hydrogels containing both drugs showed superior support for full-thickness burn regeneration, with improved wound closure, re-epithelialization, and collagen expression. The hydrogels also showed neovascularization and anti-inflammatory effects, as confirmed by CD31 and TNF-α markers. In conclusion, these dual drug-delivery hydrogels showed significant potential as wound dressings for full-thickness wounds. [ABSTRACT FROM AUTHOR]

Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Regeneration of large bone defects is challenging in the next few years because the age of the population is growing. Bone grafting as a gold standard of bone repairing is limited as a result of many disadvantages. In recent years, many novel materials and processing methods have been introduced to construct the native bone extracellular matrix (ECM) and restore the functions of degenerated bone. Silk fibroin (SF) as a natural polymer, has established a good reputation for bone tissue engineering applications due to its many unique properties, including exceptional biocompatibility, biodegradability, mechanical behavior, and ease of processability. In this review, recent advances in the design and application of SF-based scaffolds for bone regeneration are discussed. [ABSTRACT FROM AUTHOR]

Despite the attractive properties of carbon nanotubes (CNTs), cytoxicity and hydrophobicity are two main considerable features which limit their application in biomedical fields. It was well established that treating CNTs with extracellular matrix components could reduce these unfavourable characteristics. In an attempt to address these issues, fibronectin (FN) with different concentrations was loaded on single walled carbon nanotubes (SWCNTs) substrate. Scanning electron microscope, atomic force microscopy (AFM), contact angles and X-ray photoelectron spectroscopy (XPS) were preformed in order to characterize FN loaded SWCNTs substrates. According to XPS and AFM results, FN could interact with SWCNTs and for this, the hydrophilicity of SWCNTs was improved. Additionally, SWCNT modified with FN showed less cytotoxicity compared with neat SWCNT. Finally, FN was shown to act as an interesting extracellular component for enhancing the biological properties of SWCNT. [ABSTRACT FROM AUTHOR]

Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Nanocarrier-based drug delivery systems, in particular nanoparticles, have generated great excitement in the field of drug delivery since they provide new opportunities to overcome the limitations of conventional delivery methods with regards to the drugs. Silk fibroin (SF) is a naturally occurring protein polymer with several unique properties that make it a suitable material for incorporation into a variety of drug delivery vehicles capable of delivering a range of therapeutic agents. SF matrices have been shown to successfully deliver anticancer drugs, small molecules, and biomolecules. This review will provide an in-depth discussion of the development of SF nanoparticle-based drug delivery systems. [ABSTRACT FROM AUTHOR]

Abstract: This study investigated the efficacy of bio-hybrid silk fibroin/Calcium phosphate/PLGA nanocomposite scaffold as vascular endothelial growth factor (VEGF) delivery system. The scaffold was fabricated using freeze-drying and electrospinning. Here, we highlight the structural changes of the scaffold using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and differential scanning calorimetry (DSC). The uniform dispersion of calcium phosohate (CaP) powder within silk fibroin (SF) solution was also confirmed using Zeta potential analysis. Moreover, good biocompatibility of osteoblast cells next to the scaffold was approved by cell adhesion, proliferation and alkaline phosphatase production. The release profile of VEGF during 28days has established the efficacy of the scaffold as a sustained delivery system. The bioactivity of the released VEGF was maintained about 83%. The histology analysis has shown that the new bone tissue formation happened in the defected site after 10weeks of implantation. Generally, our data showed that the fabricated scaffold could be considered as an effective scaffold for bone tissue engineering applications. [Copyright &y& Elsevier]

Abstract: To exploit the therapeutic potential of growth factors in tissue regeneration, it is necessary to design a porous scaffold in order to concurrently accommodate cells and release angiogenic factors in a controlled manner. In an attempt to address these issues, we developed a nanocomposite scaffold based on silk/calcium phosphate/PLGA by freeze-drying and electrospinning in order to control the release of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). The highly porous scaffold possessed appropriate chemical and physical structure as confirmed by FTIR, XRD, SEM, and Zeta potential analysis. Furthermore, the incorporation of PDGF and VEGF in the scaffold was confirmed using Raman spectroscopy while their bioactivity was maintained by 82% and 89% for up to 28 days, respectively. The release of PDGF was slower than VEGF as respected. Additionally, the scaffold could promote proliferation, alkaline phosphatase production and attachment of human osteoblast cells. Histological examination established new bone matrix formation with neovascularization in the angiogenic factors loaded scaffold after 10 weeks of implantation in rabbit model. Finally, it was considered that the fabricated nanocomposite could be useful for bone tissue engineering applications. [Copyright &y& Elsevier]

As a contribution to the functionality of nerve guide conduits (NGCs) in nerve tissue engineering, here we report a conduit processing technique through introduction and evaluation of topographical, physical and chemical cues. Porous structure of NGCs based on freeze-dried silk/single walled carbon nanotubes (SF/SWNTs) has shown a uniform chemical and physical structure with suitable electrical conductivity. Moreover, fibronectin (FN) containing nanofibers within the structure of SF/SWNT conduits produced through electrospinning process have shown aligned fashion with appropriate porosity and diameter. Moreover, fibronectin remained its bioactivity and influenced the adhesion and growth of U373 cell lines. The conduits were then implanted to 10 mm left sciatic nerve defects in rats. The histological assessment has shown that nerve regeneration has taken places in proximal region of implanted nerve after 5 weeks following surgery. Furthermore, nerve conduction velocities (NCV) and more myelinated axons were observed in SF/SWNT and SF/SWNT/FN groups after 5 weeks post implantation, indicating a functional recovery for the injured nerves. With immunohistochemistry, the higher S-100 expression of Schwann cells in SF/SWNT/FN conduits in comparison to other groups was confirmed. In conclusion, an oriented conduit of biocompatible SF/SWNT/FN has been fabricated with acceptable structure that is particularly applicable in nerve grafts. [ABSTRACT FROM AUTHOR]

Abstract: Chitosan/poly(vinyl alcohol) (CS/PVA) conjugated nerve growth factor (NGF) scaffolds for potential neural tissue engineering purposes were prepared using electrospinning. NGF was incorporated onto the electrospun nanofibers to mimic the biochemical properties of the neural tissue. Upon current protocol, cell proliferation significantly imitates by ECM surface topography, matrix porosity, surface area, and chemical structure of electrospun scaffolds. CS/PVA conjugated NGF scaffolds were further assessed in terms of attachment and proliferation of SKNMC and U373 cell lines. The thermodynamic parameters of binding of NGF on CS/PVA scaffolds and the NGF releasing rate were evaluated. It has been shown that the electrospun CS/PVA conjugated NGF nanocomposite fibers possess high surface-area-to-volume ratio to support the attachment and proliferation rate of both cell types. [Copyright &y& Elsevier]

Dual‐targeted drug delivery system has established their reputation as potent vehicles for cancer chemotherapies. Herein, gemcitabine (Gem) was conjugated to human serum albumin (HSA) via dithiodipropionic anhydride to fabricate Gem‐HSA nanoparticles. It was hypothesized that this system can enhance the low stability of Gem and can improve its intracellular delivery. Furthermore, folate was applied as targeting agent on HSA nanoparticles for increasing the tumor selectivity of Gem. To evaluate the structural properties of synthesized products, 1H NMR and FT‐IR were performed. Moreover, HPLC was implemented for confirming the conjugation between HSA and Gem. Nanoparticles have shown spherical shape with negative charge. The release rate of Gem was dependent to the concentration of glutathione and pH. Folate‐targeted HSA nanoparticles have shown higher cytotoxicity, cellular uptake, and apoptosis induction on folate receptor overexpressing MDA‐MB‐231 cells in comparison to non‐targeted nanoparticles. Finally, it is considered that the developed dual‐targeted nanoparticles would be potent in improving the stability and efficacy of intracellular delivery of Gem and its selective delivery to cancer cells. [ABSTRACT FROM AUTHOR]

Despite the progress in antibiotic treatment, it is still challenging to promote bone regeneration in the case of chronic bone infection. Here, we synthesized composite hydrogels containing silk fibroin/halloysite nanotubes loaded with vancomycin. The hydrogel possessed 79.32% porosity, acceptable cell attachment, and biocompatibility. The release kinetics of vancomycin from halloysite and halloysite embedded in hydrogel were 60% and 32.5% over 23 days, respectively. Disk diffusion also showed an appropriate antibacterial activity over 10 days. Alkaline phosphatase and Alizarin red staining proved osteoconductivity of the scaffold. Totally, the data showed that composite hydrogel can be considered for treatment of bone infection. [ABSTRACT FROM AUTHOR]

Hydrogels possessing both conductive characteristics and notable antibacterial and antioxidant properties hold considerable significance within the realm of wound healing and recovery. The object of current study is the development of conductive hydrogels with antibacterial and antioxidant properties, emphasizing their potential for effective wound healing, especially in treating third-degree burns. For this purpose, various conductive hydrogels are developed based on tragacanth and silk fibroin, with variable dopamine functionalized carboxyl-capped aniline pentamer (CAP@DA). The FTIR analysis confirms that the CAP powder was successfully synthesized and modified with DA. The results show that the incorporation of CAP@DA into hydrogels can increase the porosity and swellability of the hydrogels. Additionally, the mechanical and viscoelastic properties of the hydrogels are also improved. The release of vancomycin from the hydrogels is sustained over time, and the hydrogels are effective in inhibiting the growth of Methicillin-resistant Staphylococcus aureus (MRSA). In vitro cell studies of the hydrogels show that all hydrogels are biocompatible and support cell attachment. The hydrogels' tissue adhesiveness yielded a satisfactory hemostatic outcome in a rat-liver injury model. The third-degree burn was created on the dorsal back paravertebral region of the rats and then grafted with hydrogels. The burn was monitored for 3, 7, and 14 days to evaluate the efficacy of the hydrogel in promoting wound healing. The hydrogels revealed treatment effect, resulting in enhancements in wound closure, dermal collagen matrix production, new blood formation, and anti-inflammatory properties. Better results were obtained for hydrogel with increasing CAP@DA. In summary, the multifunctional conducive hydrogel, featuring potent antibacterial properties, markedly facilitated the wound regeneration process. [ABSTRACT FROM AUTHOR]

Overcoming bacterial infections and promoting wound healing are significant challenges in clinical practice and fundamental research. This study developed a series of enzymatic crosslinking injectable hydrogels based on silk fibroin (SF), carboxymethyl cellulose (CMC), and agarose, with the addition of polydopamine functionalized graphene oxide (GO@PDA) to endow the hydrogel with suitable conductivity and antimicrobial activity. The hydrogels exhibited suitable gelation time, stable mechanical and rheological properties, high water absorbency, and hemostatic properties. Biocompatibility was also confirmed through various assays. After loading the antibiotic vancomycin hydrochloride, the hydrogels showed sustained release and good antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The fast gelation time and desirable tissue-covering ability of the hydrogels allowed for a good hemostatic effect in a rat liver trauma model. In a rat full-thickness burn wound model, the hydrogels exhibited an excellent treatment effect, leading to significantly enhanced wound closure, collagen deposition, and granulation tissue formation, as well as neovascularization and anti-inflammatory effects. In conclusion, the antibacterial electroactive injectable hydrogel dressing, with its multifunctional properties, significantly promoted the in vivo wound healing process, making it an excellent candidate for full-thickness skin wound healing. [ABSTRACT FROM AUTHOR]

This prolonged-release profile of VEGF and lower initial burst release of this factor from the modified SF NPs might result from the more specific charge interactions between VEGF and FN than that of between SF NPs and VEGF. A controlled release of VEGF from SF NPs and FN-SF NPs could be achieved over 28 days attributed to the electrostatic interactions between VEGF and SF NPs and also the presence of VEGF specific binding site on FN. Keywords: Angiogenesis; silk fibroin; nanoparticle; fibronectin; vascular endothelial growth factor; controlled release; proliferation; ; ; ; ; ; EN Angiogenesis silk fibroin nanoparticle fibronectin vascular endothelial growth factor controlled release proliferation ZH 9223 9234 12 11/21/22 20221220 NES 221220 Introduction Angiogenesis is a complex and important biological process that can occur under physiological and pathological conditions including wound healing, the female reproductive system, ischemic heart disease, and diabetic ulcers (Jayasuriya et al. [8]; Nosrati et al. [24]). [Extracted from the article]

An aptamer (Apt) conjugated hyaluronan/chitosan nanoparticles (HACSNPs) were prepared as carrier for targeted delivery of 5-fluorouracil (5FU) to mucin1 (MUC1) overexpressing colorectal adenocarcinomas. Nanoparticles had about 181 nm size, encapsulation efficiency of 45.5 ± 2.8 and acceptable stability. Conjugation of MUC1-binding Apt to the surface of the nanoparticles was confirmed by gel electrophoresis. Toxicity and cellular uptake of nanoparticles were investigated by in vitro cytotoxicity assays and confocal scanning microscopy in (MUC1 + ) human adenocarcinoma and (MUC1 − ) Chinese hamster ovary cells. Toxicity of nanoparticles were significantly higher in comparison with free drug in both cell lines while this rising was more efficient for nanoparticles decorated with Apt in MUC1 + cell line. The same result was observed in the cellular uptake study. It could be concluded that the present system has the potential to be considered in treatment of MUC1 + colorectal adenocarcinomas. [ABSTRACT FROM AUTHOR]

[Display omitted] • Reviewed and classified green biomaterials applied for bone tissue engineering. • Discussed additive manufacturing (printing) techniques for bone implantation. • Reviewed bioprinting techniques for bone repair with bio-ceramics and biopolymers. • Classified 3D, 4D, 5D, and 6D bioprinting techniques for bone repair/regeneration. • Classified bone fracture, healing and state-of-the-art features of bone repair. Despite exceptional self-regeneration properties of bone, severe injuries often require additional surgical intervention such as using artificial bone constructs. These structures need to meet structural and performance requirements. Moreover, when implanted, the rate and the mechanism of erosion and fracture of bone constructs should be optimized for stimulating the regeneration of defected bone and, more critically, providing support in the interim. Technological development in the fields of imaging and additive manufacturing revolutionized manufacturing personalized implants with characteristics matching the requirements of target injuries. From biomaterials point of view, greener and more sustainable biomaterials from renewable resources are on demand for bone regeneration; moreover, bone repair should meed engineering features like mechanical and load-bearing properties. Currently, potential processing methods are not limited to 3D printing, but include 4D and 5D printers by changing the time, dimension, and rotational degrees of freedom of printing machines. Several innovative processes and techniques enabled the application of metals, their alloys, ceramics, and polymers, providing an extremely wide spectrum of possibilities for designing bone implant. Herein, the critical aspects of biomaterials applied in bone tissue engineering, their application in bone repair and regeneration are summarized, and novel directions in bone tissue engineering based on green biomaterials are proposed for future developments. Eventually, the latest advances in the application of green biomaterials in clinics are outlined. [ABSTRACT FROM AUTHOR]

Agarose is a prominent marine polysaccharide representing reversible thermogelling behavior, outstanding mechanical properties, high bioactivity, and switchable chemical reactivity for functionalization. As a result, agarose has received particular attention in the fabrication of advanced delivery systems as sophisticated carriers for therapeutic agents. The ever-growing use of agarose-based biomaterials for drug delivery systems resulted in rapid growth in the number of related publications, however still, a long way should be paved to achieve FDA approval for most of the proposed products. This review aims at a classification of agarose-based biomaterials and their derivatives applicable for controlled/targeted drug delivery purposes. Moreover, it attempts to deal with opportunities and challenges associated with the future developments ahead of agarose-based biomaterials in the realm of advanced drug delivery. Undoubtedly, this class of biomaterials needs further advancement, and a lot of critical questions have yet to be answered. Unlabelled Image [ABSTRACT FROM AUTHOR]

Gene therapy, including small interfering RNA (siRNA) technology, is one of the leading strategies that help to improve the outcomes of the current therapeutic systems against HIV‐1 infection. The successful therapeutic application of siRNAs requires their safe and efficient delivery to specific cells. Here, we introduce a superparamagnetic iron oxide nanoparticle (SPION) for delivering siRNA against HIV‐1 nef (anti‐nef siRNA) into two cell lines, HEK293 and macrophage RAW 264.7. SPIONs were coated with trimethyl chitosan (TMC), and thereafter, different concentrations of SPION–TMC were coated with different ratios of a carboxymethyl dextran (CMD) to modify the physicochemical properties and improve the biological properties of the nanocarriers. The nanoparticles exhibited a spherical shape with an average size of 112 nm. The obtained results showed that the designed delivery route enhanced the uptake of siRNA into both HEK293 and RAW 264.7 cells compared with control groups. Moreover, CMD–TMC–SPIONs containing anti‐nef siRNA significantly reduced the expression of HIV‐1 nef in HEK293 stable cells. The modified siRNA‐loaded SPIONs also displayed no toxicity or apoptosis‐inducing effects on the cells. The CMD–TMC–SPIONs are suggested as potential nanocarriers for siRNA delivery in gene therapy of HIV‐1 infection. [ABSTRACT FROM AUTHOR]

Abstract Nowadays, regenerating peripheral nerves injuries (PNIs) remain a major clinical challenge, which has gained a great attention between scientists. Here, we represent a nanocomposite based on silk fibroin reinforced gold nanorods (SF/GNRs) to evaluate the proliferation and attachment of PC12 cells. The morphological characterization of nanocomposites with transmission electron microscopy (TEM) and Scanning electron microscopy (SEM) showed that the fabricated scaffolds have porous structure with interconnected pores that is suitable for cell adhesion and growth. GNRs significantly improved the poor electrical conductivity of bulk silk fibroin scaffold. Evaluating the morphology of PC12 cells on the scaffold also confirmed the normal morphology of cells with good rate of adhesion. SF/GNRs nanocomposites showed better cellular attachment, growth and proliferation without any toxicity compared with bulk SF scaffold. Moreover, immunostaining studies represented the overexpression of neural specific proteins like nestin and neuron specific enolase (NSE) in the cells cultured on SF/GNRs nanocomposites in comparison to neat SF scaffolds. Graphical abstract A scheme of in vitro study of SF/GNRs nanocomposites including SF extraction, GNPs fabrication, incorporating GNPs into Silk-Fibrin, seeding and culturing the PC12 cells in these nanocomposites. Unlabelled Image [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • PEGylation increased affinity of APOs family to nanoplatforms. • Polypeptide as surface modification changed affinity of corona proteins to nanoplatform in order to improve cellular uptake. • Corona protected of therpeutic agents from further interaction with biological fluid in the transfection process. • Low power thermal therapy enhanced the therapeutic release. Abstract Interaction of nanoplatforms with biomolecules in biological fluids alters nanoplatforms approach to target tissue and deliver their cargo. Here in, three nanoplatforms were utilized as a carrier to detect the effects of subsequent biomolecules on gene delivery using NIR thermal therapy. Nanoplatforms included; graphene oxide coated gold nanorods (NR@GO), PEGylated NR@GO (NR@GO-PEG) and poly L arginine functionalized NR@GO-PEG (NR@GO-PEG-PLArg). Results indicated that incubation of nanoplatforms in different concentrations of human plasma induced the evolution of layer of proteins (corona) with different thickness on the surface of nanoplatforms. Protein corona decreased the surface charge and optical properties of nanoplatforms. Corona subunits of ITIH, HAS and APOs protein family were extracted from NR@GO-PEG-PLArg surface that play a major role in cellular internalization of nanoplatforms. Moreover, NR@GO-PEG-PLArg remarkably targeted the cancer cells due to uncovered long linear chains of targeting agent (PLArg). The process of gene release and activating apoptotic pathway were enhanced by NIR thermal therapy, which could disrupt the electrostatic interactions and release the protein corona and genes from the surface of nanoplatforms. In conclusion, modification of nanoplatforms with targeting agents could alter the composition of corona toward well interaction with cell and deliver the therapeutic agent. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFUs) often remain untreated because they are difficult to heal, caused by reduced skin sensitivity and impaired blood vessel formation. In this study, we propose a novel approach to manage DFUs using a multifunctional hydrogel made from a combination of alginate and gum arabic. To enhance the healing properties of the hydrogel, we immobilized nerve growth factor (NGF), within specially designed mesoporous silica nanoparticles (MSN). The MSNs were then incorporated into the hydrogel along with carnosine (Car), which further improves the hydrogel's therapeutic properties. The hydrogel containing the immobilized NGF (SiNGF) could control the sustain release of NGF for >21 days, indicating that the target hydrogel (AG-Car/SiNGF) can serve as a suitable reservoir managing diabetic wound regeneration. In addition, Car was able to effectively reduce inflammation and significantly increase angiogenesis compared to the control group. Based on the histological results obtained from diabetic rats, the target hydrogel (AG-Car/SiNGF) reduced inflammation and improved re-epithelialization, angiogenesis, and collagen deposition. Specific staining also confirmed that AG-Car/SiNGF exhibited improved tissue neovascularization, transforming growth factor-beta (TGFβ) expression, and nerve neurofilament. Overall, our research suggests that this newly developed composite system holds promise as a potential treatment for non-healing diabetic wounds. [Display omitted] [ABSTRACT FROM AUTHOR]