Uncovering the protective mechanism of baicalin in treatment of fatty liver based on network pharmacology and cell model of NAFLD.

Excessive nonesterified fatty acids (NEFA) impair cellular metabolism and will induce fatty liver formation in dairy cows during the periparturient. Baicalin, an active flavonoid, has great potential efficacy in alleviating lipid accumulation and ameliorating the development of fatty liver disease. Nevertheless, its mechanism remains unclear. Here, the potential mechanism of baicalin on system levels was explored using network pharmacology and in vitro experiments. Firstly, the target of baicalin and fatty liver disease was predicted, and then the protein-protein interaction (PPI) network was constructed. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) (q-value) pathway enrichment is performed through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server. Finally, the results of the network analysis of the in vitro treatment of bovine hepatocytes by NEFA were confirmed. The results showed that 33 relevant targets of baicalin in the treatment of liver fatty were predicted by network pharmacology, and the top 20 relevant pathways were extracted by KEGG database. Baicalin treatment can reduce triglyceride (TAG) content and lipid droplet accumulation in NEFA-treated bovine hepatocytes, and the mechanism is related to inhibiting lipid synthesis and promoting lipid oxidation. The alleviating effect of baicalin on fatty liver may be related to the up-regulation of solute vector family member 4 (SLC2A4), Down-regulated AKT serine/threonine kinase 1 (AKT1), Peroxisome proliferator-activated receptor gamma (PPARG), Epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF), Interleukin 6 (IL-6) were associated. These results suggested that baicalin may modulate key inflammatory markers, and lipogenesis processes to prevent fatty liver development in dairy cows.

Elastic Nanofibrous Dressings with Mesenchymal Stem Cell-Recruiting and Protecting Characteristics for Promoting Diabetic Wound Healing.

Diabetic wounds that do not heal for a long time challenge global healthcare. Mesenchymal stem cell (MSC) therapy has positive significance in promoting diabetic wound healing. However, traditional MSC therapy involves exogenous MSCs, which brings many limitations and unsatisfactory treatment. Moreover, the maintenance of MSC viability and function is difficult because of the high level of reactive oxygen species (ROS) in diabetic wounds. Therefore, we developed a nanofibrous dressing to recruit and protect endogenous MSCs while avoiding the inherent disadvantages of exogenous MSCs. Ceria nanoparticles capable of ROS scavenging are integrated into the nanofibrous dressings, together with Apt19S, a DNA aptamer with affinity and selectivity for MSCs. In addition, the homogenization and freeze-drying technology give the nanofibrous dressings good elasticity, which protects the wound from external pressure. Further experiments in diabetic mice show that the dressing has excellent endogenous MSC recruitment and anti-inflammatory properties, thereby synergistically promoting diabetic wound healing. This study is expected to explore an efficient method of stem cell therapy, providing a new way to construct high-performance wound dressings.

A transparent p-coumaric acid-grafted-chitosan coating with antimicrobial, antioxidant and antifogging properties for fruit packaging applications.

The study aimed to develop a novel, transparent and non-toxic coating with antimicrobial, antioxidant, and antifogging properties. The p-coumaric acid-grafted chitosan (CS-PCA) was synthesized via a carbodiimide coupling reaction and then characterized. The CS-PCA coatings were further prepared using the casting method. The CS-PCA coatings obtained exhibited excellent transparency, UV-light barrier ability, and antifogging properties, as confirmed by spectroscopy and antifogging tests. The CS-PCA coatings showed stronger antioxidant capacity and antimicrobial properties against Escherichia coli, Staphylococcus aureus and Botrytis cinerea compared to CS. The multifunctional coatings were further coated on the polyethylene cling film and their effectiveness was confirmed through a strawberry preservation test. The decay of the strawberries was reduced by CS-PCA coated film at room temperature.

Hydrophobic Cross-Linked Chains Regulate High Wet Tissue Adhesion Hydrogel with Toughness, Anti-hydration for Dynamic Tissue Repair.

Hydrogel adhesion materials are widely reported for tissue engineering repair applications, however, wet tissue surface moisture can reduce the wet-adhesion properties and mechanical strength of hydrogels limiting their application. Here, anti-hydration gelatin-acrylic acid-ethylene dimethacrylate (GAE) hydrogels with hydrophobic cross-linked chains are constructed. The prepared GAE hydrogel is soaked in PBS (3 days) with a volume change of 0.6 times of the original and the adhesive strength, Young's modulus, toughness, and burst pressure are maintained by ≈70% of the original. A simple and universal method is used to introduce hydrophobic chains as cross-linking points to prepare hydrogels with anti-hydration, toughness, and high wet state adhesion. The hydrophobic cross-linked chains not only restrict the movement of molecular chains but also hinder the intrusion of water molecules. Antihydration GAE hydrogels exhibit good biocompatibility, slow drug release, and dynamic oral wet-state tissue repair properties. Therefore, the anti-hydration hydrogel has excellent toughness, wet tissue adhesion properties, and good prospects for biological applications.

Multifunctional wet-adhesive chitosan/acrylic conduit for sutureless repair of peripheral nerve injuries.

The incidence of peripheral nerve injury (PNI) is high worldwide, and a poor prognosis is common. Surgical closure and repair of the affected area are crucial to ensure the effective treatment of peripheral nerve injuries. Despite being the standard treatment approach, reliance on sutures to seal the severed nerve ends introduces several limitations and restrictions. This technique is intricate and time-consuming, and the application of threading and punctate sutures may lead to tissue damage and heightened tension concentrations, thus increasing the risk of fixation failure and local inflammation. This study aimed to develop easily implantable chitosan-based peripheral nerve repair conduits that combine acrylic acid and cleavable N-hydroxysuccinimide to reduce nerve damage during repair. In ex vivo tissue adhesion tests, the conduit achieved maximal interfacial toughness of 705 J m-2 ± 30 J m-2, allowing continuous bridging of the severed nerve ends. Adhesive repair significantly reduces local inflammation caused by conventional sutures, and the positive charge of chitosan disrupts the bacterial cell wall and reduces implant-related infections. This promises to open new avenues for sutureless nerve repair and reliable medical implants.

The Pharmacological Efficacy of Baicalin in Inflammatory Diseases.

Baicalin is one of the most abundant flavonoids found in the dried roots of Scutellaria baicalensis Georgi (SBG) belonging to the genus Scutellaria. While baicalin is demonstrated to have anti-inflammatory, antiviral, antitumor, antibacterial, anticonvulsant, antioxidant, hepatoprotective, and neuroprotective effects, its low hydrophilicity and lipophilicity limit the bioavailability and pharmacological functions. Therefore, an in-depth study of baicalin's bioavailability and pharmacokinetics contributes to laying the theoretical foundation for applied research in disease treatment. In this view, the physicochemical properties and anti-inflammatory activity of baicalin are summarized in terms of bioavailability, drug interaction, and inflammatory conditions.

A Network Pharmacology and Multi-Omics Combination Approach to Reveal the Effect of Strontium on Ca2+ Metabolism in Bovine Rumen Epithelial Cells.

Strontium (Sr) belongs to the same group in the periodic table as calcium (Ca). Sr level can serve as an index of rumen Ca absorption capacity; however, the effects of Sr on Ca2+ metabolism are unclear. This study aims to investigate the effect of Sr on Ca2+ metabolism in bovine rumen epithelial cells. The bovine rumen epithelial cells were isolated from the rumen of newborn Holstein male calves (n = 3, 1 day old, 38.0 ± 2.8 kg, fasting). The half maximal inhibitory concentration (IC50) of Sr-treated bovine rumen epithelial cells and cell cycle were used to establish the Sr treatment model. Transcriptomics, proteomics, and network pharmacology were conducted to investigate the core targets of Sr-mediated regulation of Ca2+ metabolism in bovine rumen epithelial cells. The data of transcriptomics and proteomics were analyzed using bioinformatic analysis (Gene Ontology and Kyoto Encyclopedia of genes/protein). Quantitative data were analyzed using one-way ANOVA in GraphPad Prism 8.4.3 and the Shapiro-Wilk test was used for the normality test. Results presented that the IC50 of Sr treatment bovine rumen epithelial cells for 24 h was 43.21 mmol/L, and Sr increased intracellular Ca2+ levels. Multi-omics results demonstrated the differential expression of 770 mRNAs and 2436 proteins after Sr treatment; network pharmacology and reverse transcriptase polymerase chain reaction (RT-PCR) revealed Adenosylhomocysteine hydrolase-like protein 2 (AHCYL2), Semaphoring 3A (SEMA3A), Parathyroid hormone-related protein (PTHLH), Transforming growth factor ß2 (TGF-ß2), and Cholesterol side-chain cleavage enzyme (CYP11A1) as potential targets for Sr-mediated Ca2+ metabolism regulation. Together these results will improve the current comprehension of the regulatory effect of Sr on Ca2+ metabolism and pave a theoretical basis for Sr application in bovine hypocalcemia.

Mimosa-Inspired Stimuli-Responsive Curling Bioadhesive Tape Promotes Peripheral Nerve Regeneration.

Trauma often results in peripheral nerve injuries (PNIs). These injuries are particularly challenging therapeutically because of variable nerve diameters, slow axonal regeneration, infection of severed ends, fragility of the nerve tissue, and the intricacy of surgical intervention. Surgical suturing is likely to cause additional damage to peripheral nerves. Therefore, an ideal nerve scaffold should possess good biocompatibility, diameter adaptability, and a stable biological interface for seamless biointegration with tissues. Inspired by the curl of Mimosa pudica, this study aimed to design and develop a diameter-adaptable, suture-free, stimulated curling bioadhesive tape (SCT) hydrogel for repairing PNI. The hydrogel is fabricated from chitosan and acrylic acid-N-hydroxysuccinimide lipid via gradient crosslinking using glutaraldehyde. It closely matches the nerves of different individuals and regions, thereby providing a bionic scaffold for axonal regeneration. In addition, this hydrogel rapidly absorbs tissue fluid from the nerve surface achieving durable wet-interface adhesion. Furthermore, the chitosan-based SCT hydrogel loaded with insulin-like growth factor-I effectively promotes peripheral nerve regeneration with excellent bioactivity. This procedure for peripheral nerve injury repair using the SCT hydrogel is simple and reduces the difficulty and duration of surgery, thereby advancing adaptive biointerfaces and reliable materials for nerve repair.

New techniques and methods for prevention and treatment of symptomatic traumatic neuroma: A systematic review.

Generally, axons located at the central end of the nerve system will sprout after injury. Once these sprouts cannot reach the distal end of the severed nerve, they will form a traumatic neuroma. Traumatic neuromas bring a series of complex symptoms to patients, such as neuropathic pain, skin abnormalities, skeletal abnormalities, hearing loss, and visceral damage. To date, the most promising and practical clinical treatments are drug induction and surgery, but both have their limitations. Therefore, it will be the mainstream trend to explore new methods to prevent and treat traumatic neuroma by regulating and remodeling the microenvironment of nerve injury. This work first summarized the pathogenesis of traumatic neuroma. Additionally, the standard methods of prevention and treatment on traumatic neuroma were analyzed. We focused on three essential parts of advanced functional biomaterial therapy, stem cell therapy, and human-computer interface therapy to provide the availability and value of preventing and treating a traumatic neuroma. Finally, the revolutionary development of the prevention and treatment on traumatic neuroma has been prospected. How to transform the existing advanced functional materials, stem cells, and artificial intelligence robots into clinical practical technical means as soon as possible for high-quality nerve repair and prevention of neuroma was further discussed.

Using bimetallic Au/Cu nanoplatelets for construction of facile and label-free inner filter effect-based photoluminescence sensing platform for sarcosine detection.

Herein, we report a facile and label-free method for sensitive and specific determination of prostate cancer biomarker sarcosine via using photoluminescent bimetallic Au/Cu nanoplatelets (AuCu NPs) to construct an inner filter effect (IFE)-based photoluminescence (PL) sensing platform. The AuCu NPs were formed by the cysteine-induced co-reduction reaction, which displayed bright PL with an emission peak at 560 nm. Meanwhile, the Cu(I) doping caused a maximum 25-fold enhancement of quantum yield (QY), compared with the native Au(I) complexes, i.e., from 0.85 to 21.5%. By integrating the AuCu NPs with p-phenylenediamine (PPD) oxidation reaction, an IFE-based sensor for sarcosine detection was constructed. In this method, sarcosine is oxidized under the catalysis of sarcosine oxidase (SOx) to yield H2O2. The latter further oxidizes PPD to form 2,5-diamino-N,N'-bis(p-aminophenyl)-l,4-benzoquinone di-imine (PPDox) in the presence of horseradish peroxidase (HRP). The UV-vis absorption spectrum of the PPDox can overlap well with the excitation and emission spectra of the AuCu NPs, resulting in the efficient quenching of the AuCu NPs via the IFE effect. Therefore, this IFE-based AuCu NPs/SOx/PPD/HRP sensing platform can be used for highly sensitive and specific sensing of sarcosine. The sensing platform showed two linear regions of the PL intensity of the AuCu NPs versus the concentration of sarcosine in the range of 0.5-5 µM and 5-100 µM with a detection limit (LOD) of 0.12 µM (S/N = 3). Furthermore, this IFE-based sensing platform could be developed into a paper-based biosensor for simple, instrument-free, and visual detection of sarcosine.

Rapid detection of miRNA via development of consecutive adenines (polyA)-based electrochemical biosensors.

Herein, we report rapid electrochemical detection of miRNA let-7a based on a DNA probe consisting of a polyA and Fc-co-labeled harpin structure (the polyA-H probe). The polyA-H probe could be facilely immobilized on Au surfaces through the interactions between polyA and Au, followed by its pre-hybridization with a single strand (S1). The probe's surface density could be optimized for minimizing steric hindrance via changing the polyA block length. The target let-7a could be rapidly amplified via loop-mediated isothermal amplification (LAMP) with four simplified primers, followed by inducing the formation of dimeric i-motif (DIM) structure via H+-induced rapid folding of two C-rich sequences of motif strand 1 and strand 2. It was found that, after introducing the as-formed DIM to hybridize the S1, the immobilized polyA20-H probe could rapidly revert to its hairpin structure, sending out a turn-on electrochemical signal of the Fc. The total time for detecting the let-7a was around 80 min, obviously less than that of most of electrochemical DNA sensors reported previously. The biosensor showed a linear relationship of the current response to the let-7a in the range of 10 fM to 50 nM with a limit of detection (LOD) of 5.1 fM. Our biosensors were further tested using human serum spiked with the let-7a and the extracts of the breast adenocarcinoma cells spiked with and without the let-7a, respectively. Satisfied results were obtained. This study shows a potential promising future of development of electrochemical biosensors for rapid detection of miRNAs in the application of clinical practice.

Chitin conduits modified with DNA-peptide coating promote the peripheral nerve regeneration.

Peripheral nerve injury (PNI) is one of the common clinical injuries which needs to be addressed. Previous studies demonstrated the effectiveness of using biodegradable chitin (CT) conduits small gap tubulization technology as a substitute for traditional epineurial neurorrhaphy. Aiming to improve the effectiveness of CT conduits in repairing PNI, we modified their surface with a DNA-peptide coating. The coating consisted of single strand DNA (ssDNA) and its complementary DNA'-peptide mimics. First, we immobilize ssDNA (DNA1 + 2) on CT conduits by carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) method to construct CT/DNA conduits. EDC/NHS was used to activate carboxyl groups of modified ssDNA for direct reaction with primary amines on the CT via amide bond formation. Then, DNA1'-BDNF + DNA2'-VEGF mimic peptide (RGI + KLT) were bonded to CT/DNA conduits by complementary base pairing principle at room temperature to form CT/RGI + KLT conduits. When the surrounding environment rose to a certain point (37 °C), the CT/RGI + KLT conduits achieved sustainable release of DNA'-peptide.In vitro, the CT conduits modified with the DNA-peptide coating promoted the proliferation and secretion of Schwann cells by maintaining their repair state. It also promoted the proliferation of human umbilical vein vessel endothelial cells and axon outgrowth of dorsal root ganglion explants.In vivo, CT/RGI + KLT conduits promoted regeneration of injured nerves and functional recovery of target muscles, which was facilitated by the synergistic contribution of angiogenesis and neurogenesis. Our research brings DNA and DNA-peptide hybrids into the realm of tissue engineering to repair PNI.

XT-type DNA hydrogels loaded with VEGF and NGF promote peripheral nerve regeneration via a biphasic release profile.

Peripheral nerve injury (PNI) remains an unresolved challenge in the medicine area. With the development of biomaterial science and tissue engineering, a variety of nerve conduits were widely applied for repairing long defect PNI. DNA materials are developing rapidly due to their multiple advantages. In the present study, we aim to combine a DNA hydrogel, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) to construct a new type of delivery system, which could achieve a biphasic release profile of VEGF and NGF by taking advantage of the different degradation rates between X- and T-type DNA. In vitro results showed that the DNA gel + VEGF/NGF system could promote proliferation, migration and myelination of Rat Schwann cells (RSC) while maintaining cell viability. In vivo results indicated a better effect of DNA gel + VEGF/NGF on promoting repair of long defect PNI than the hollow chitin conduits (CT), DNA gel or VEGF/NGF group. The new technology invention holds promising clinical application prospects for repairing PNI and may be used broadly after step-by-step improvement.

Strongly phosphorescent and water-soluble gold(I)-silver(I)-cysteine nanoplatelets via versatile small biomolecule cysteine-assisted synthesis for intracellular hypochlorite detection.

In biological systems, abnormal levels of hypochlorite (ClO-) could result in cell dysfunctions. Herein, we report a facile, one-step and green approach based on the versatile small biomolecule cysteine both serving as reducing agent and ligand for synthesizing the strongly photoluminencent and water-soluble Au(I)-Ag(I)-cysteine complexes nanoplatelets (Au(I)-Ag(I)-Cys nanoplatelets) for intracellular hypochlorite detection. Multiple spectroscopic and microscopical tools have been used to characterize the resultant Au(I)-Ag(I)-Cys nanoplatelets. It was found that with the cysteine-assisted synthesis approach, the Ag(I) doping to the Au(I) complexes could form the supramolecular organometallic nanoplatelets. Inside, the Au(I)-Ag(I) metallophilic interactions showing an Au to Ag charge transfer property were formed, thereby enhancing the photoluminescence (PL) intensity via the charge transfer from the bioligand's S to the metal-metal center. The quantum yield (QY) was measured to show a maximum 16-fold enhancement (i.e., from 0.85 to 13.8%). Interestingly, in the presence of ClO-, the metal-thiolate ligand structure of the as-synthesized Au(I)-Ag(I)-Cys nanoplatelets could be oxidatively damaged, causing the PL quenching, thereby producing the effect of biorecognition towards ClO- anions. The ClO--induced PL quenching produced two linear regions at ClO- concentrations of 0.01-5.0 µM and 5.0-1000 µM with a limit of detection (LOD) of 8.0 nM (S/N = 3). The ClO--induced PL quenching was specific over the other typical reactive oxygen species (ROS) and the potential interfering substances in biological samples. In addition, the Au(I)-Ag(I)-Cys nanoplatelets had good biocompatibility. Thus, they could be further developed as a biosensor for detecting endogenous ClO- anions in living cells.

An injectable and biodegradable nano-photothermal DNA hydrogel enhances penetration and efficacy of tumor therapy.

The biological barrier of solid tumors hinders deep penetration of nanomedicine, constraining anticancer treatment. Moreover, the inherent multidrug resistance (MDR) of cancer tissues may further limit the efficacy of anti-tumor nanomedicine. We synthesized highly permeable, photothermal, injectable, and positively charged biodegradable nucleic acid hydrogel (DNA-gel) nanoparticles to deliver cancer drugs. The nanoparticles are derived from photothermal materials containing black phosphorus quantum dots (BPQDs). The intra-tumoral BPQDs improve the sensitivity of tumor cells to photothermal therapy (PTT) and photodynamic treatment (PDT). Tumor cells take up the positively charged and controllable size DNA-gel nanoparticles, facilitating easy penetration and translocation of the particles across and within the cells. Mouse models demonstrated the anti-tumor activity of the DNA gel nanoparticles in vivo. In particular, the DNA gel nanoparticles enhanced clearance of both small and large tumor masses. Just 20 days after treatment, the tumor masses had been cleared. Compared to DOX chemotherapy alone, the DNA-gel treatment also significantly reduced drug resistance and improved the overall survival of mice with orthotopic breast tumors (83.3%, 78 d). Therefore, DNA gel nanoparticles are safe and efficient supplements for cancer therapy.

Biphasic synthesis of biodegradable urchin-like mesoporous organosilica nanoparticles for enhanced cellular internalization and precision cascaded therapy.

It is widely accepted that a small particle size and rough surface can enhance tumor tissue accumulation and tumor cellular uptake of nanoparticles, respectively. Herein, sub-50 nm urchin-inspired disulfide bond-bridged mesoporous organosilica nanoparticles (UMONs) featured with a spiky surface and glutathione (GSH)-responsive biodegradability were successfully synthesized by a facile one-pot biphasic synthesis strategy for enhanced cellular internalization and tumor accumulation. l-Arginine (LA) is encapsulated into the mesopores of UMONs, whose outer surface is capped with the gatekeeper of ultrasmall gold nanoparticles, i.e., UMONs-LA-Au. On the one hand, the mild acidity-activated uncapping of ultrasmall gold can realize a tumor microenvironment (TME)-responsive release of LA. On the other hand, the unique natural glucose oxidase (GOx)-mimicking catalytic activity of ultrasmall gold can catalyze the decomposition of intratumoral glucose to produce acidic hydrogen peroxide (H2O2) and gluconic acid. Remarkably, these products can not only further facilitate the release of LA, but also catalyze the LA-H2O2 reaction for an increased nitric oxide (NO) yield, which realizes synergistic catalysis-enhanced NO gas therapy for tumor eradication. The judiciously fabricated UMONs-LA-Au present a paradigm of TME-responsive nanoplatforms for both enhanced cellular uptake and tumor-specific precision cascaded therapy, which broadens the range of practical biomedical applications and holds a significant promise for the clinical translation of silica-based nanotheranostics.

Controllable synthesis of versatile mesoporous organosilica nanoparticles as precision cancer theranostics.

Despite the advantages of mesoporous silica nanoparticles (MSNs) in drug delivery, the inherent non-biodegradability seriously impedes the clinical translation of inorganic MSNs, so the current research focus has been turned to mesoporous organosilica nanoparticles (MONs) with higher biocompatibility and easier biodegradability. Recent remarkable advances in silica fabrication chemistry have catalyzed the emergence of a library of MONs with various structures and functions. This review will summarize the latest state-of-the-art studies on the precise control of morphology, structure, framework, particle size and pore size of MONs, which enables the precise synthesis of MONs with suitable engineering for precision stimuli-responsive drug delivery/release, bioimaging and synergistic therapy. Besides, the potential challenges about the future development of MONs are also outlooked with the intention of attracting more researchers to promote the clinical translation of MONs.

Functional DNA-based hydrogel intelligent materials for biomedical applications.

Deoxyribonucleic acid (DNA) nanotechnology is a relevant research field of nano-biotechnology, which has developed rapidly in recent years. Researchers have studied DNA far more than they have studied its genetic characteristics, and now it has evolved into the field of nanomedical materials. A variety of articles based on DNA nanostructures can be obtained by rational design and controllable preparation. In particular, intelligent DNA-based hydrogel materials have attracted significant attention as an essential representative of macro DNA materials. They have shown a wide range of applications, especially in the field of biomedical applications. DNA-based hydrogels have many unique and fascinating properties, such as, excellent biocompatibility, biodegradability, basic programmability, catalytic activities, therapeutic potential, and molecular recognition and bonds. The intelligent DNA hydrogel will undergo abrupt changes in the stimulation of temperature, pH value, ionic strength, and solvent composition. These factors can also be used for applications in intelligent materials that play an essential role in biomedical sciences. To date, intelligent DNA hydrogels have been reported for many applications, including controlled drug delivery, targeted gene therapy, cancer therapy, biosensors, protein production, and 3D cell cultures. However, the large-scale production of intelligent DNA hydrogels has not yet been realized, and the synergistic multifunctional integration has not been explored. This review summarizes the current state of DNA nanostructures, especially the intelligent DNA-based hydrogel materials, and focuses on design and engineering for bio-responsive use and proposes some reasonable prospects for the future development of intelligent DNA-based hydrogel materials.

Cellular Nanofiber Structure with Secretory Activity-Promoting Characteristics for Multicellular Spheroid Formation and Hair Follicle Regeneration.

Multicellular spheroids can mimic the in vivo microenvironment and maintain the unique functions of tissues, which has attracted great attention in tissue engineering. However, the traditional culture microenvironment with structural deficiencies complicates the culture and collection process and tends to lose the function of multicellular spheroids with the increase of cell passage. In order to construct efficient and functional multicellular spheroids, in this study, a chitosan/polyvinyl alcohol nanofiber sponge which has an open-cell cellular structure is obtained. The hair follicle (HF) regeneration model was employed to evaluate HF-inducing ability of dermal papilla (DP) multicellular spheroids which formed on the cellular structure nanofiber sponge. Through structural fine-tuning, the nanofiber sponge has appropriate elasticity for the creation of a three-dimensional dynamic microenvironment to regulate cellular behavior. The cellular structure nanofiber sponge tilts the balance of cell-substratum and cell-cell interactions to a state which is more conducive to the formation of controllable multicellular spheroids in a short time. More importantly, it improves the secretory activity of high-passaged dermal papilla cells and restores their intrinsic properties. Experiments using BALB/c nude mice show that cultured DP multicellular spheroids could effectively enhance HF-inducing ability. This novel system provides a simple and efficient strategy for multicellular spheroid formation and HF regeneration.

A controllable local drug delivery system based on porous fibers for synergistic treatment of melanoma and promoting wound healing.

A dual function system that inhibits tumor growth while promoting wound healing is very necessary for melanoma treatment since tumor killing and skin healing are two complementary and influential processes. Herein, a controllable local drug delivery system based on porous fiber membranes incorporated with CuS nanoparticles is designed for chemo-photothermal synergistic melanoma therapy and promoting wound healing. The porous structure on the fiber surface significantly increases the drug loading capacity of the membrane and the photothermal effect of incorporated CuS nanoparticles is used to control the drug release rate. Benefitting from the chemo-photothermal synergistic therapy, the composite membrane can effectively kill melanoma cells in vitro and inhibit tumor growth in vivo. Furthermore, the membrane can also significantly promote the cutaneous wound healing by providing mechanical support and releasing copper ions. Thus, this work provides new ideas for the development of multifunctional local treatment and postoperative care systems.