Photoactive Poly-L-Lysine gel with resveratrol-magnesium metal polyphenol network: A promising strategy for preventing tracheal anastomotic complications following surgery.

Postoperative complications at the anastomosis site following tracheal resection are a prevalent and substantial concern. However, most existing solutions primarily focus on managing symptoms, with limited attention given to proactively preventing the underlying pathological processes. To address this challenge, we conducted a drug screening focusing on clinically-relevant polyphenolic compounds, given the growing interest in polyphenolic compounds for their potential role in tissue repair during wound healing. This screening led to the identification of resveratrol as the most promising candidate for mitigating tracheal complications, as it exhibited the most significant efficacy in enhancing the expression of vascular endothelial growth factor (VEGF) while concurrently suppressing the pivotal fibrosis factor: transforming growth factor-beta 1 (TGF-ß1), showcasing its robust potential in addressing these issues. Building upon this discovery, we further developed an innovative photosensitive poly-L-lysine gel integrated with a resveratrol-magnesium metal polyphenol network (MPN), named Res-Mg/PL-MA. This design allows for the enables sustained release of resveratrol and synergistically enhances the expression of VEGF and also promotes resistance to tensile forces, aided by magnesium ions, in an anastomotic tracheal fistula animal models. Moreover, the combination of resveratrol and poly-L-lysine hydrogel effectively inhibits bacteria, reduces local expression of key inflammatory factors, and induces polarization of macrophages toward an anti-inflammatory phenotype, as well as inhibits TGF-ß1, consequently decreasing collagen production levels in an animal model of post-tracheal resection. In summary, our novel Res-Mg/PL-MA hydrogel, through antibacterial, anti-inflammatory, and pro-vascularization mechanisms, effectively prevents complications at tracheal anastomosis, offering significant promise for translational applications in patients undergoing tracheal surgeries.

Exudate Absorbing and Antimicrobial Hydrogel Integrated with Multifunctional Curcumin-Loaded Magnesium Polyphenol Network for Facilitating Burn Wound Healing.

Burns are among the most common causes of trauma worldwide. Reducing the healing time of deep burn wounds has always been a major challenge. Traditional dressings not only require a lengthy medical procedure but also cause unbearable pain and secondary damage to patients. In this study, we developed an exudate-absorbing and antimicrobial hydrogel with a curcumin-loaded magnesium polyphenol network (Cur-Mg@PP) to promote burn wound healing. That hydrogel was composed of an ε-poly-l-lysine (ε-PLL)/polymer poly(γ-glutamic acid) (γ-PGA) hydrogel (PP) and curcumin-loaded magnesium polyphenol network (Cur-Mg). Because of the strong water absorption property of ε-PLL and γ-PGA, Cur-Mg@PP powder can quickly absorb the wound exudate and transform into a moist and viscous hydrogel, thus releasing payloads such as magnesium ion (Mg2+) and curcumin (Cur). The released Mg2+ and Cur demonstrated good therapeutic efficacy on analgesic, antioxidant, anti-inflammation, angiogenesis, and tissue regeneration. Our findings provide a strategy for accelerating burn wound healing.

Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions.

Lymph nodes (LNs) are important hubs for metastatic cell arrest and growth, immune modulation, and secondary dissemination to distant sites through a series of mechanisms, and it has been proved that lymph node metastasis (LNM) is an essential prognostic indicator in many different types of cancer. Therefore, it is important for oncologists to understand the mechanisms of tumor cells to metastasize to LNs, as well as how LNM affects the prognosis and therapy of patients with cancer in order to provide patients with accurate disease assessment and effective treatment strategies. In recent years, with the updates in both basic and clinical studies on LNM and the application of advanced medical technologies, much progress has been made in the understanding of the mechanisms of LNM and the strategies for diagnosis and treatment of LNM. In this review, current knowledge of the anatomical and physiological characteristics of LNs, as well as the molecular mechanisms of LNM, are described. The clinical significance of LNM in different anatomical sites is summarized, including the roles of LNM playing in staging, prognostic prediction, and treatment selection for patients with various types of cancers. And the novel exploration and academic disputes of strategies for recognition, diagnosis, and therapeutic interventions of metastatic LNs are also discussed.

Biodegradable Implants for Internal Fixation of Fractures and Accelerated Bone Regeneration.

Bone fractures have always been a burden to patients due to their common occurrence and severe complications. Traditionally, operative treatments have been widely used in the clinic for implanting, despite the fact that they can only achieve bone fixation with limited stability and pose no effect on promoting tissue growth. In addition, the nondegradable implants usually need a secondary surgery for implant removal, otherwise they may block the regeneration of bones resulting in bone nonunion. To overcome the low degradability of implants and avoid multiple surgeries, tissue engineers have investigated various biodegradable materials for bone regeneration, whereas the significance of stability of long-term bone fixation tends to be neglected during this process. Combining the traditional orthopedic implantation surgeries and emerging tissue engineering, we believe that both bone fixation and bone regeneration are indispensable factors for a successful bone repair. Herein, we define such a novel idea as bone regenerative fixation (BRF), which should be the main future development trend of biodegradable materials.

Multifunctional calcium polyphenol networks reverse the hostile microenvironment of trauma for preventing postoperative peritoneal adhesions.

Abdominal adhesions, a commonly observed complication of abdominal surgery, have a high incidence and adversely affect patients' physical and mental health. The primary causes of abdominal adhesions are intraoperative trauma, acute inflammatory response, bleeding, and foreign body infection. Because most current treatment approaches for abdominal adhesions are limited, improved and novel postoperative anti-adhesion regimens are urgently needed. In this study, we developed calcium polyphenol network (CaPN) microspheres based on the self-assembly of the natural triphenolic compound gallic acid and Ca2+ in solution. The physicochemical properties of CaPNs, including their hemostatic, antibacterial, antioxidant, and anti-inflammatory activities, were investigated in vitro. Bleeding and cecal-abdominal wall adhesion models were established to observe the hemostatic activity of CaPNs and their preventive effect on postoperative abdominal wall adhesion in vivo. The results showed that CaPNs significantly reduced inflammation, oxidative stress, fibrosis, and abdominal adhesion formation and had good hemostatic and antibacterial properties. Our findings suggest a novel strategy for the prevention of postoperative adhesions.

Wet-adhesive γ-PGA/ε-PLL hydrogel loaded with EGF for tracheal epithelial injury repair.

Following the global COVID-19 pandemic, the incidence of tracheal epithelial injury is increasing. However, the repair of tracheal epithelial injury remains a challenge due to the slow renewal rate of tracheal epithelial cells (TECs). In traditional nebulized inhalation treatments, drugs are enriched in the lungs or absorbed into the blood, reducing drug concentration at the tracheal injury site. In this study, we prepared an epidermal growth factor (EGF)-loaded gamma-polyglutamic acid (γ-PGA)/epsilon-poly-L-lysine (ε-PLL) (PP) hydrogel (EGF@PP) to promote the repair of tracheal epithelial injury. Epidermal growth factor promotes the proliferation of TECs and enhances vascularization, thereby accelerating injury repair. The PP hydrogel exhibits outstanding wet adhesion, slow drug release, and antibacterial and anti-inflammatory properties, making it suitable for application in the airways and creating an environment conducive to epithelial repair. Here, we established a rabbit model of tracheal injury using a laser to destroy the tracheal epithelium and delivered EGF@PP powder to the injury site under fiberoptic bronchoscopy guidance. Our findings revealed that this was an effective therapeutic strategy for accelerating the repair of tracheal epithelial injury.

Curcumin-zinc framework encapsulated microneedle patch for promoting hair growth.

Hair loss is a growing esthetic condition driven by complex mechanisms that has numerous psycho-social implications. Conventional drug applications usually focus on a single treatment target, and the penetration depth restricts the post-delivery effect. Method: We fabricated a curcumin-zinc framework (ZnMOF) encapsulated gamma-polyglutamic acid (γ-PGA) microneedle patch (ZnMOF-MN) as a multifunctional biosafe transdermal drug delivery system. ZnMOF was characterized with the field emission scanning electron microscope (FE-SEM), dynamic light scattering (DLS), elemental mapping, and X-ray diffraction (XRD). The topographical and hygroscopic features of ZnMOF-MN were characterized with SEM. The in vitro ZnMOF release profile and the in vivo penetration of ZnMOF-MN were also evaluated. The anti-oxidant, anti-apoptosis, and antiandrogen effects of ZnMOF solution and ZnMOF-MN extract were studied on mouse dermal papilla cells (DPCs). Two animal models (in C57BL/6 mice), including androgenic alopecia (AGA) model and wound healing model, were used to identify the therapeutic effect of ZnMOF-MN on hair regrowth and wound healing in vivo. Hair follicles, surrounding vessels (CD31+), and proliferating cells (Ki67+) were evaluated by histological staining. Results: ZnMOF crystals were cone-shaped nanoparticles with a size distribution of 424.9 ± 59.01 nm. ZnMOF-MN patch can create temporary holes in the skin to directly and evenly deliver bioactive ZnMOF particles to the targeted depth and achieve a steady and sustained release of Zn2+ and curcumin. In vitro, ZnMOF significantly improved the viability of DPCs against the excess reactive oxygen species (ROS) and inhibited the apoptosis induced by zinc deficiency. In addition, it also reversed the inhibitory effects of dihydrotestosterone (DHT) infiltration. Moreover, the ZnMOF-MN treatment has been proved to accelerate wound healing and increase hair follicles in wound healing models, and improved the hair regrowth in AGA animal models. Enhanced capillary density and cell proliferation observed in the CD31+ and Ki67+ staining of ZnMOF-MN group in both animal models also suggested that ZnMOF can facilitate angiogenesis and promote cell proliferation in the skin, respectively. Conclusion: The ZnMOF-MN treatment is a comprehensive solution with excellent therapeutic efficacy and patient-friendly features for promoting hair growth under various clinical conditions.

Carnobacterium maltaromaticum boosts intestinal vitamin D production to suppress colorectal cancer in female mice.

Carnobacterium maltaromaticum was found to be specifically depleted in female patients with colorectal cancer (CRC). Administration of C. maltaromaticum reduces intestinal tumor formation in two murine CRC models in a female-specific manner. Estrogen increases the attachment and colonization of C. maltaromaticum via increasing the colonic expression of SLC3A2 that binds to DD-CPase of this bacterium. Metabolomic and transcriptomic profiling unveils the increased gut abundance of vitamin D-related metabolites and the mucosal activation of vitamin D receptor (VDR) signaling in C. maltaromaticum-gavaged mice in a gut microbiome- and VDR-dependent manner. In vitro fermentation system confirms the metabolic cross-feeding of C. maltaromaticum with Faecalibacterium prausnitzii to convert C. maltaromaticum-produced 7-dehydrocholesterol into vitamin D for activating the host VDR signaling. Overall, C. maltaromaticum colonizes the gut in an estrogen-dependent manner and acts along with other microbes to augment the intestinal vitamin D production to activate the host VDR for suppressing CRC.

Construction of 3D-Bioprinted cartilage-mimicking substitute based on photo-crosslinkable Wharton's jelly bioinks for full-thickness articular cartilage defect repair.

Three-dimensional (3D) bioprinted cartilage-mimicking substitutes for full-thickness articular cartilage defect repair have emerged as alternatives to in situ defect repair models. However, there has been very limited breakthrough in cartilage regeneration based on 3D bioprinting owing to the lack of ideal bioinks with printability, biocompatibility, bioactivity, and suitable physicochemical properties. In contrast to animal-derived natural polymers or acellular matrices, human-derived Wharton's jelly is biocompatible and hypoimmunogenic with an abundant source. Although acellular Wharton's jelly can mimic the chondrogenic microenvironment, it remains challenging to prepare both printable and biologically active bioinks from this material. Here, we firstly prepared methacryloyl-modified acellular Wharton's jelly (AWJMA) using a previously established photo-crosslinking strategy. Subsequently, we combined methacryloyl-modified gelatin with AWJMA to obtain a hybrid hydrogel that exhibited both physicochemical properties and biological activities that were suitable for 3D bioprinting. Moreover, bone marrow mesenchymal stem cell-loaded 3D-bioprinted cartilage-mimicking substitutes had superior advantages for the survival, proliferation, spreading, and chondrogenic differentiation of bone marrow mesenchymal stem cells, which enabled satisfactory repair of a model of full-thickness articular cartilage defect in the rabbit knee joint. The current study provides a novel strategy based on 3D bioprinting of cartilage-mimicking substitutes for full-thickness articular cartilage defect repair.

Oxidative Stimuli-Responsive "Pollen-Like" Exosomes from Silver Nanoflowers Remodeling Diabetic Wound Microenvironment for Accelerating Wound Healing.

The hostile oxidative wound microenvironment, defective angiogenesis, and uncontrolled release of therapeutic factors are major challenges in improving the diabetic wound healing. Herein, adipose-derived-stem-cell-derived exosomes (Exos) are first loaded into Ag@bovine serum albumin (BSA) nanoflowers (Exos-Ag@BSA NFs) to form a protective "pollen-flower" delivery structure, which are further encapsulated into the injectable collagen (Col) hydrogel (Exos-Ag@BSA NFs/Col) for concurrent remodeling of the oxidative wound microenvironment and precise release of Exos. The Exos-Ag@BSA NFs can selectively dissociate in an oxidative wound microenvironment, which triggers sustained release of Ag ions (Ag+ ) and cascades controllable release of "pollen-like" Exos at the target site, thus protecting Exos from oxidative denaturation. Such a wound-microenvironment-activated release property of Ag+ and Exos effectively eliminates bacteria and promotes the apoptosis of impaired oxidative cells, resulting in improved regenerative microenvironment. Additionally, Exos-Ag@BSA NFs/Col markedly accelerates wound healing and regeneration in vivo in a diabetic murine silicone-splinted excisional wound model by promoting blood perfusion, tissue granulation, collagen deposition, neovascularization, angiogenesis, and re-epithelization. It is anticipated that this work will inspire the development of more delicate and disease-specific therapeutic systems for clinical wound management.

In situ electrospun aloe-nanofiber membrane for chronic wound healing.

Alleviating excessive inflammation while accelerating chronic wound healing to prevent wound infection has remained challenging, especially during the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 when patients experienced difficulties with receive appropriate healthcare. We addressed this issue by developing handheld electrospun aloe-nanofiber membranes (ANFMs) with convenient, environmentally friendly properties and a therapeutic capacity for wound closure. Our results showed that ANFMs fabricated with high molecular weight polyvinyl alcohol (PVA) to form fibers during electrospinning had uniform fibrous architecture and a porous structure. Given the value of aloe gel in accelerating wound healing, liquid extracts from ANFMs significantly downregulated the expression of the pro-inflammatory genes, interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), and markedly suppress the generation of reactive oxygen species (ROS) induced by lipopolysaccharide in RAW264.7 macrophages. These results indicated the excellent antioxidant and anti-inflammatory effects of ANFMs. After implantation into a mouse diabetic wound model for 12 days in situ, ANFMs notably expedited chronic wound healing via promoting angiogenesis and enhancing cell viability. Our ANFMs generated by handheld electrospinning in situ healed chronic wounds offer a convenient and promising alternative for patients to heal their own wounds under variable conditions.

Intelligent microneedle patch with prolonged local release of hydrogen and magnesium ions for diabetic wound healing.

Diabetes mellitus, an epidemic with a rapidly increasing number of patients, always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization, decreased angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Herein, a poly (lactic-co-glycolic acid) (PLGA)-based microneedle patch loaded with magnesium hydride (MgH2) (MN-MgH2) is manufactured for defeating diabetic wounds. The application of microneedle patch contributes to the transdermal delivery and the prolonged release of MgH2 that can generate hydrogen (H2) and magnesium ions (Mg2+) after reaction with body fluids. The released H2 reduces the production of ROS, transforming the pathological microenvironment induced by diabetes mellitus. Meanwhile, the released Mg2+ promotes the polarization of pro-healing M2 macrophages. Consequently, cell proliferation and migration are improved, and angiogenesis and tissue regeneration are enhanced. Such intelligent microneedle patch provides a novel way for accelerating wound healing through steadily preserving and releasing of H2 and Mg2+ locally and sustainably.

A highly selective fluorescent sensor for chlortetracycline based on histidine-templated copper nanoclusters.

In this study, histidine-protected copper nanoclusters (Cu NCs@His) were established by using a one-pot method, which histidine and ascorbic acid were applied as the template and reducing agent, respectively. The as-developed Cu NCs@His endued green emission wavelength at 494 nm with the excitation of 378 nm. The Cu NCs@His exhibited green fluorescence under UV light (365 nm). Using Cu NCs@His as a pattern nanosensor, the fluorescent "turn off" mechanism was fabricated for the determination of chlortetracycline in the light of the linear decrease of fluorescence intensities around 494 nm. The chlortetracycline conducted as a quencher, leading to reveal an excellent linear relationship between ln(F0/F) of Cu NCs@His and chlortetracycline concentrations with the range of 0.5-200 µM, and the detection limit was 0.876 µM. The fluorescence quenching of Cu NCs@His revealed excellent selectivity for chlortetracycline over other potential interfering substances in the human body. This strategy was exhibited to be a convenient sensing platform for the detection of chlortetracycline in real medical samples, which could unfold a brand new and direct system for the sensing of chlortetracycline in real samples.

MXenes-integrated microneedle combined with asiaticoside to penetrate the cuticle for treatment of diabetic foot ulcer.

Patients with diabetic foot ulcers usually suffer from inefficient epithelisation and angiogenesis accompanied by chronic wound healing. Diabetic foot ulcers remain a major challenge in clinical medicine; however, traditional treatments are incapable of transdermal drug delivery, resulting in a low drug delivery rate. We report the development of Ti2C3 MXenes-integrated poly-γ-glutamic acid (γ-PGA) hydrogel microneedles to release asiaticoside (MN-MXenes-AS). Asiaticoside was loaded into PGA-MXenes hydrogel to facilitate cell proliferation while regulating angiogenesis. The characterisation and mechanical strength of the microneedles were investigated in vitro, and the wound-healing efficacy of the microneedles was confirmed in diabetic mice. MXenes significantly improved the mechanical strength of microneedles, while γ-PGA hydrogels provided a moist microenvironment for wound healing. Mice treated with MN-MXenes-AS demonstrated obvious improvements in wound healing process. We successfully fabricated an MXenes-integrated microneedle that possesses sufficient rigidity to penetrate the cuticle for subcutaneous drug delivery, thereby accelerating diabetic wound healing. We demonstrated that MN-MXenes-AS is effective in promoting growth both in vivo and in vitro. Collectively, our data show that MN-MXenes-AS accelerated the healing of diabetic foot ulcers, supporting the use of these microneedles in the treatment of chronic wounds.

3'untranslated regions of tumor suppressor genes evolved specific features to favor cancer resistance.

Cancer-related genes have evolved specific genetic and genomic features to favor tumor suppression. Previously we reported that tumor suppressor genes (TSGs) acquired high promoter CpG dinucleotide frequencies during evolution to maintain high expression in normal tissues and resist cancer-specific downregulation. In this study, we investigated whether 3'untranslated regions (3'UTRs) of TSGs have evolved specific features to carry out similar functions. We found that 3'UTRs of TSGs, especially those involved in multiple histological types and pediatric cancers, are longer than those of non-cancer genes. 3'UTRs of TSGs also exhibit higher density of binding sites for RNA-binding proteins (RBPs), particularly those having high affinities to C-rich motifs. Both longer 3'UTR length and RBP binding sites enrichment are correlated with higher gene expression in normal tissues across tissue types. Moreover, both features together with the correlated N6-methyladenosine modification and the extent of protein-protein interactions are positively associated with the ability of TSGs to resist cancer-specific downregulation. These results were successfully validated with independent datasets. Collectively, these findings indicate that TSGs have evolved longer 3'UTR with increased propensity to RBP binding, N6-methyladenosine modification and protein-protein interactions for optimizing their tumor-suppressing functions.

Use of mesoporous polydopamine nanoparticles as a stable drug-release system alleviates inflammation in knee osteoarthritis.

Osteoarthritis drugs are often short-acting; therefore, to enhance their efficacy, long-term, stable-release, drug-delivery systems are urgently needed. Mesoporous polydopamine (MPDA), a natural nanoparticle with excellent biocompatibility and a high loading capacity, synthesized via a self-aggregation-based method, is frequently used in tumor photothermal therapy. Here, we evaluated its efficiency as a sustained and controlled-release drug carrier and investigated its effectiveness in retarding drug clearance. To this end, we used MPDA as a controlled-release vector to design a drug-loaded microsphere system (RCGD423@MPDA) for osteoarthritis treatment, and thereafter, tested the efficacy of the system in a rat model of osteoarthritis. The results indicated that at an intermediate drug-loading dose, MPDA showed high drug retention. Furthermore, the microsphere system maintained controlled drug release for over 28 days. Our in vitro experiments also showed that drug delivery using this microsphere system inhibited apoptosis-related cartilage degeneration, whereas MPDA-only administration did not show obvious cartilage degradation improvement effect. Results from an in vivo osteoarthritis model also confirmed that drug delivery via this microsphere system inhibited cartilage damage and proteoglycan loss more effectively than the non-vectored drug treatment. These findings suggest that MPDA may be effective as a controlled-release carrier for inhibiting the overall progression of osteoarthritis. Moreover, they provide insights into the selection of drug-clearance retarding vectors, highlighting the applicability of MPDA in this regard.

One-step synthesis of blue emission copper nanoclusters for the detection of furaltadone and temperature.

Polyvinyl pyrrolidone (PVP), playing roles as a templating agent, can be applied to prepare blue-emitting copper nanoclusters (Cu NCs@PVP) on the basis of a rapid chemical reduction synthesis method. The Cu NCs@PVP displayed a blue emission wavelength at 430 nm and the corresponding quantum yield (QY) could reach 10.4%. Subsequently, the as-synthesized Cu NCs@PVP were used for the trace analysis of furaltadone based on the inner filter effect (IFE) between Cu NCs@PVP and furaltadone, which caused the fluorescence to be effectively quenched. Additionally, this proposed determination platform based on the Cu NCs@PVP for furaltadone sensing possessed an excellent linear range from 0.5 to 100 µM with a lower detection limit of 0.045 µM (S/N = 3). Meanwhile, the Cu NCs@PVP also could be applied for the sensing of temperature. Furthermore, the practicability of the sensing platform has been successfully verified by measuring furaltadone in real samples, affirming its potential to increase fields for the determination of furaltadone.

Synergistic effects of mechanical stimulation and crimped topography to stimulate natural collagen development for tendon engineering.

Suitable scaffold structures and mechanical loading are essential for functional tendon engineering. However, the bipolar fibril structure of native tendon collagen is yet to be recaptured in engineered tendons. This study compared the development of Achilles tendons of postnatal rats with and without (via surgical section) mechanical loading to define the mechanism of mechanical stimulation-mediated tendon development. The results demonstrated that the severed tendons weakened mechanically and exhibited disorganization without a bipolar fibril superstructure. Proteomic analysis revealed differentially expressed key regulatory molecules related to the collagen assembly process, including decreased fibromodulin, keratocan, fibroblast growth factor-1, and increased lumican and collagen5a1 in the severed tendons with immunohistochemical verification. Additionally, a complex regulatory network of mechanical stimulation-mediated collagen assembly in a spatiotemporal manner was also revealed using bioinformatics analysis, wherein PI3K-Akt and HDAC4 may be the predominant signaling pathways. A wavy microgrooved surface (Y = 5.47sin(0.015x)) that biomimics tendon topography was observed to enhance the expression of collagen assembly molecules under mechanical loading, and the aforementioned pathways are particularly involved and verified with their respective inhibitors of LY-294002 and LMK-235. Furthermore, an electrospun crimped nanofiber scaffold (approximately 2 µm fiber diameter and 0.12 crimpness) was fabricated to biomimic the tenogenic niche environment; this was observed to be more effective on enhancing collagen production and assembly under mechanical stimulation. In conclusion, the synergistic effect between topographical niche and mechanical stimulation was observed to be essential for collagen assembly and maturation and should be applied to functional tendon engineering in the future. STATEMENT OF SIGNIFICANCE: In biomaterial-mediated tendon regeneration, mechanical stimulation is essential for tendon collagen assembly. However, the underlying mechanisms remain not fully defined, leading to the failure of the native-like collagen regeneration. In this study, a mechanical stimulation deprivation model of rat tendon was established to reveal the mechanisms in tendon development and define the key regulatory molecules including small leucine-rich proteoglycans, lysyl oxidase and collagen V. After ensuring the importance of biomimetic structure in tendon remodeling, crimped nanofibers were developed to verify these regulatory molecules, and demonstrated that mechanical stimulation significantly enhanced collagen assembly via PIK3 and HDAC4 pathways in biomaterial-regulated tendon regeneration. This study provides more insightful perspectives in the physiologically remodeling progression of tendon collagen and design of tendon scaffolds.

Carboxymethyl chitosan-grafted polyvinylpyrrolidone-iodine microspheres for promoting the healing of chronic wounds.

Chronic wounds that fail to heal are the most common complications experienced by diabetic patients, and current treatment remains unsatisfactory, mainly due to the vulnerability of diabetic wounds to bacterial infections. Chitosan derivatives are widely used to treat chronic wounds due to their excellent hydrophilicity, biodegradability, and antimicrobial activity and substantial contribution to tissue regeneration. However, the antimicrobial effect of chitosan is not sufficient due to the complicated pathological mechanism of diabetes mellitus. Here, we prepared carboxymethyl chitosan-grafted polyvinylpyrrolidone-iodine (CMC-g-PVPI) microspheres and used them to treat chronic wounds. Carboxymethyl chitosan (CMC) was used as the skeleton and was grafted with polyvinylpyrrolidone-iodine (PVPI) to form a CMC-g-PVPI complex hydrogel and CMC-g-PVPI microspheres, which formed as a result of the high shearing dispersion of the complex hydrogel. In vivo experiments on diabetic wounds revealed significantly accelerated wound closure in the presence of the microspheres, demonstrating the excellent potential of CMC-g-PVPI to promote skin wound regeneration under diabetic conditions.