A Redox-Triggered Autophagy-Induced Nanoplatform with PD-L1 Inhibition for Enhancing Combined Chemo-Immunotherapy.

Epirubicin (EPI) alone can trigger mildly protective autophagy in residual tumor cells, resulting in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and leads to antiprogrammed death ligand 1 (anti-PD-1)/PD-L1 therapy resistance, posing a significant clinical challenge in tumor immunotherapy. The combination of checkpoint inhibitors targeting the PD-1/PD-L1 pathway and amplifying autophagy presents an innovative approach to tumor treatment, which can prevent tumor immune escape and enhance therapeutic recognition. Herein, we aimed to synthesize a redox-triggered autophagy-induced nanoplatform with SA&EA-induced PD-L1 inhibition. The hyaluronic acid (HA) skeleton and arginine segment promoted active nanoplatform targeting, cell uptake, and penetration. The PLGLAG peptide was cleaved by overexpressing matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment, and the PD-L1 inhibitor D-PPA was released to inhibit tumor immune escape. The intense autophagy inducers, STF-62247 and EPI, were released owing to the cleavage of disulfide bonds influenced by the high glutathione (GSH) concentration in tumor cells. The combination of EPI and STF induced apoptosis and autophagic cell death, effectively eliminating a majority of tumor cells. This indicated that the SA&EA nanoplatform has better therapeutic efficacy than the single STF@AHMPP and EPI@AHMPTP groups. This research provided a way to set up a redox-triggered autophagy-induced nanoplatform with PD-L1 inhibition to enhance chemo-immunotherapy.

3D printing of customized bioceramics for promoting bone tissue regeneration by regulating sympathetic nerve behavior.

Numerous studies have shown that there are multiple neural activities involved in the process of bone resorption and bone regeneration, and promoting osteogenesis by promoting neural network reconstruction is an effective strategy for repairing critical size bone defects. However, traumatic bone defects often cause activation of the sympathetic nervous system (SNS) in the damaged area, releasing excess catecholamines (CAs), resulting in a decrease in the rate of bone formation. Herein, a 3D-printed scaffold loaded with propranolol (PRN) is proposed to reduce CA concentrations in bone defect areas and promote bone regeneration through drug release. For this purpose, PRN-loaded methacrylated gelatin (GelMA) microspheres were mixed with low-concentration GelMA and perfused into a 3D-printed porous hydroxyapatite (HAp) scaffold. By releasing PRN, which can block ß-adrenergic receptors, it hinders the activation of sympathetic nerves and inhibits the release of excess CA by the SNS. At the same time, the composite scaffold recruits bone marrow mesenchymal stem cells (BMSCs) and promotes the differentiation of BMSCs in the direction of osteoblasts, which effectively promotes bone regeneration in the rabbit femoral condyle defect model. The results of the study showed that the release of PRN from the composite scaffold could effectively hinder the activation of sympathetic nerves and promote bone regeneration, providing a new strategy for the treatment of bone defects.

An injectable cartilage-coating composite with long-term protection, effective lubrication and chondrocyte nourishment for osteoarthritis treatment.

The osteoarthritic (OA) environment within articular cartilage poses significant challenges, resulting in chondrocyte dysfunction and cartilage matrix degradation. While intra-articular injections of anti-inflammatory drugs, biomaterials, or bioactive agents have demonstrated some effectiveness, they primarily provide temporary relief from OA pain without arresting OA progression. This study presents an injectable cartilage-coating composite, comprising hyaluronic acid and decellularized cartilage matrix integrated with specific linker polymers. It enhances the material retention, protection, and lubrication on the cartilage surface, thereby providing an effective physical barrier against inflammatory factors and reducing the friction and shear force associated with OA joint movement. Moreover, the composite gradually releases nutrients, nourishing OA chondrocytes, aiding in the recovery of cellular function, promoting cartilage-specific matrix production, and mitigating OA progression in a rat model. Overall, this injectable cartilage-coating composite offers promising potential as an effective cell-free treatment for OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) in the articular cartilage leads to chondrocyte dysfunction and cartilage matrix degradation. This study introduces an intra-articular injectable composite material (HDC), composed of decellularized cartilage matrix (dECMs), hyaluronan (HA), and specially designed linker polymers to provide an effective cell-free OA treatment. The linker polymers bind HA and dECMs to form an integrated HDC structure with an enhanced degradation rate, potentially reducing the need for frequent injections and associated trauma. They also enable HDC to specifically coat the cartilage surface, forming a protective and lubricating layer that enhances long-term retention, acts as a barrier against inflammatory factors, and reduces joint movement friction. Furthermore, HDC nourishes OA chondrocytes through gradual nutrient release, aiding cellular function recovery, promoting cartilage-specific matrix production, and mitigating OA progression.

DLP Fabrication of Multiple Hierarchical Biomimetic GelMA/SilMA/HAp Scaffolds for Enhancing Bone Regeneration.

Severe bone defects resulting from trauma and diseases remain a persistent clinical challenge. In this study, a hierarchical biomimetic microporous hydrogel composite scaffold was constructed by mimicking the hierarchical structure of bone. Initially, gelatin methacrylamide (GelMA) and methacrylic anhydride silk fibroin (SilMA) were synthesized, and GelMA/SilMA inks with suitable rheological and mechanical properties were prepared. Biomimetic micropores were then generated by using an aqueous two-phase emulsification method. Subsequently, biomimetic microporous GelMA/SilMA was mixed with hydroxyapatite (HAp) to prepare biomimetic microporous GelMA/SilMA/HAp ink. Hierarchical biomimetic microporous GelMA/SilMA/HAp (M-GSH) scaffolds were then fabricated through digital light processing (DLP) 3D printing. Finally, in vitro experiments were conducted to investigate cell adhesion, proliferation, and inward migration as well as osteogenic differentiation and vascular regeneration effects. In vivo experiments indicated that the biomimetic microporous scaffold significantly promoted tissue integration and bone regeneration after 12 weeks of implantation, achieving 42.39% bone volume fraction regeneration. In summary, this hierarchical biomimetic microporous scaffold provides a promising strategy for the repair and treatment of bone defects.

An injectable photocuring silk fibroin-based hydrogel for constructing an antioxidant microenvironment for skin repair.

Skin has a protein microenvironment dominated by functional collagen fibers, while oxidative stress caused by injury can greatly slow down the progress of wound healing. Here, methacrylated dopamine was incorporated into methacrylated silk fibroin molecule chains to develop an injectable hydrogel with photocuring properties for constructing an antioxidant skin protein microenvironment. This silk fibroin-based hydrogel (SF-g-SDA) showed good tensile and adhesion properties for adapting to the wound shape and skin movement, exhibited stable mechanical properties, good biodegradability and cytocompatibility, and promoted cell adhesion and vascularization in vitro. In addition, its phenolic hydroxyl-mediated antioxidant properties effectively protected cells from damage caused by oxidative stress and supported normal cellular life activities. In animal experiments, SF-g-SDA achieved better skin repair effects in comparison to commercial Tegaderm™ in vivo, showing its ability to accelerate wound healing, improve collagen deposition and alignment in newly fabricated tissues, and promote neovascularization and hair follicle formation. These experimental results indicated that the SF-g-SDA hydrogel is a promising wound dressing.

Molecular co-assembled strategy tuning protein conformation for cartilage regeneration.

The assembly of oligopeptide and polypeptide molecules can reconstruct various ordered advanced structures through intermolecular interactions to achieve protein-like biofunction. Here, we develop a "molecular velcro"-inspired peptide and gelatin co-assembly strategy, in which amphiphilic supramolecular tripeptides are attached to the molecular chain of gelatin methacryloyl via intra-/intermolecular interactions. We perform molecular docking and dynamics simulations to demonstrate the feasibility of this strategy and reveal the advanced structural transition of the co-assembled hydrogel, which brings more ordered ß-sheet content and 10-fold or more compressive strength improvement. We conduct transcriptome analysis to reveal the role of co-assembled hydrogel in promoting cell proliferation and chondrogenic differentiation. Subcutaneous implantation evaluation confirms considerably reduced inflammatory responses and immunogenicity in comparison with type I collagen. We demonstrate that bone mesenchymal stem cells-laden co-assembled hydrogel can be stably fixed in rabbit knee joint defects by photocuring, which significantly facilitates hyaline cartilage regeneration after three months. This co-assembly strategy provides an approach for developing cartilage regenerative biomaterials.

Engineered Microchannel Scaffolds with Instructive Niches Reinforce Endogenous Bone Regeneration by Regulating CSF-1/CSF-1R Pathway.

Structural and physiological cues provide guidance for the directional migration and spatial organization of endogenous cells. Here, a microchannel scaffold with instructive niches is developed using a circumferential freeze-casting technique with an alkaline salting-out strategy. Thereinto, polydopamine-coated nano-hydroxyapatite is employed as a functional inorganic linker to participate in the entanglement and crystallization of chitosan molecules. This scaffold orchestrates the advantage of an oriented porous structure for rapid cell infiltration and satisfactory immunomodulatory capacity to promote stem cell recruitment, retention, and subsequent osteogenic differentiation. Transcriptomic analysis as well as its in vitro and in vivo verification demonstrates that essential colony-stimulating factor-1 (CSF-1) factor is induced by this scaffold, and effectively bound to the target colony-stimulating factor-1 receptor (CSF-1R) on the macrophage surface to activate the M2 phenotype, achieving substantial endogenous bone regeneration. This strategy provides a simple and efficient approach for engineering inducible bone regenerative biomaterials.

Hierarchical Scaffold with Directional Microchannels Promotes Cell Ingrowth for Bone Regeneration.

Bone regenerative scaffolds with a bionic natural bone hierarchical porous structure provide a suitable microenvironment for cell migration and proliferation. Here, a bionic scaffold (DP-PLGA/HAp) with directional microchannels is prepared by combining 3D printing and directional freezing technology. The 3D printed framework provides structural support for new bone tissue growth, while the directional pore embedded in the scaffolds provides an express lane for cell migration and nutrition transport, facilitating cell growth and differentiation. The hierarchical porous scaffolds achieve rapid infiltration and adhesion of bone marrow mesenchymal stem cells (BMSCs) and improve the expression of osteogenesis-related genes. The rabbit cranial defect experiment presents significant new bone formation, demonstrating that DP-PLGA/HAp offers an effective means to guide cranial bone regeneration. The combination of 3D printing and directional freezing technology might be a promising strategy for developing bone regenerative biomaterials.

A facile Immunoregulatory Constructional Design by Proanthocyanidin Optimizing Directional Chitosan Microchannel.

Improving the interconnected structure and bioregulatory function of natural chitosan is beneficial for optimizing its performance in bone regeneration. Here, a facile immunoregulatory constructional design is proposed for developing instructive chitosan by directional freezing and alkaline salting out. The molecular dynamics simulation confirmed the assembly kinetics and structural features of various polyphenols and chitosan molecules. Along with the in vitro anti-inflammatory, antioxidative, promoting bone mesenchymal stem cell (BMSC) adhesion and proliferation performance, proanthocyanidin optimizing chitosan (ChiO) scaffold presented an optimal immunoregulatory structure with the directional microchannel. Transcriptome analysis in vitro further revealed the cytoskeleton- and immune-regulation effect of ChiO are the key mechanism of action on BMSC. The rabbit cranial defect model (Φ = 10 mm) after 12 weeks of implantation confirmed the significantly enhanced bone reconstitution. This facile immunoregulatory directional microchannel design provides effective guidance for developing inducible chitosan scaffolds.

Injectable Microgels with Hybrid Exosomes of Chondrocyte-Targeted FGF18 Gene-Editing and Self-Renewable Lubrication for Osteoarthritis Therapy.

Abnormal silencing of fibroblast growth factor (FGF) signaling significantly contributes to joint dysplasia and osteoarthritis (OA); However, the clinical translation of FGF18-based protein drugs is hindered by their short half-life, low delivery efficiency and the need for repeated articular injections. This study proposes a CRISPR/Cas9-based approach to effectively activate the FGF18 gene of OA chondrocytes at the genome level in vivo, using chondrocyte-affinity peptide (CAP) incorporated hybrid exosomes (CAP/FGF18-hyEXO) loaded with an FGF18-targeted gene-editing tool. Furthermore, CAP/FGF18-hyEXO are encapsulated in methacrylic anhydride-modified hyaluronic (HAMA) hydrogel microspheres via microfluidics and photopolymerization to create an injectable microgel system (CAP/FGF18-hyEXO@HMs) with self-renewable hydration layers to provide persistent lubrication in response to frictional wear. Together, the injectable CAP/FGF18-hyEXO@HMs, combined with in vivo FGF18 gene editing and continuous lubrication, have demonstrated their capacity to synergistically promote cartilage regeneration, decrease inflammation, and prevent ECM degradation both in vitro and in vivo, holding great potential for clinical translation.

Hollow Copper Sulfide Photothermal Nanodelivery Platform Boosts Angiogenesis of Diabetic Wound by Scavenging Reactive Oxygen Species.

Sharply rising oxidative stress and ineffectual angiogenesis have imposed restrictions on diabetic wound healing. Here, a photothermal-responsive nanodelivery platform (HHC) was prepared by peroxidase (CAT)-loaded hollow copper sulfide dispersed in photocurable methacrylamide hyaluronan. The HHC could scavenge reactive oxygen species (ROS) and promote angiogenesis by photothermally driven CAT and Cu2+ release. Under near-infrared light irradiation, the HHC presented safe photothermal performance (<43 °C), efficient bacteriostatic ability against E. coli and S. aureus. It could rapidly release CAT into the external environment for decomposing H2O2 and oxygen generation to alleviate oxidative stress while promoting fibroblast migration and VEGF protein expression of endothelial cells by reducing intracellular ROS levels. The nanodelivery platform presented satisfactory therapeutic effects on murine diabetic wound healing by modulating tissue inflammation, promoting collagen deposition and increasing vascularization in the neodermis. This HHC provided a viable strategy for diabetic wound dressing design.

Nucleation Domains in Biomineralization: Biomolecular Sequence and Conformational Features.

Biomolecules play a vital role in the regulation of biomineralization. However, the characteristics of practical nucleation domains are still sketchy. Herein, the effects of the representative biomolecular sequence and conformations on calcium phosphate (Ca-P) nucleation and mineralization are investigated. The results of computer simulations and experiments prove that the line in the arrangement of dual acidic/essential amino acids with a single interval (Bc (Basic) -N (Neutral) -Bc-N-Ac (Acidic)- NN-Ac-N) is most conducive to the nucleation. 2α-helix conformation can best induce Ca-P ion cluster formation and nucleation. "Ac- × × × -Bc" sequences with α-helix are found to be the features of efficient nucleation domains, in which process, molecular recognition plays a non-negligible role. It further indicates that the sequence determines the potential of nucleation/mineralization of biomolecules, and conformation determines the ability of that during functional execution. The findings will guide the synthesis of biomimetic mineralized materials with improved performance for bone repair.

Cationic Biopolymeric Scaffold of Chelating Nanohydroxyapatite Self-Regulates Intraoral Microenvironment for Periodontal Bone Regeneration.

Periodontal bone defect is a common but longstanding healthcare issue since traditional bone grafts have limited functionalities in regulating complex intraoral microenvironments. Here, a porous cationic biopolymeric scaffold (CSC-g-nHAp) with microenvironment self-regulating ability was synthesized by chitosan-catechol chelating the Ca2+ of nanohydroxyapatite and bonding type I collagen. Chitosan-catechol's inherent antibacterial and antioxidant abilities endowed this scaffold with desirable abilities to eliminate periodontal pathogen infection and maintain homeostatic balances between free radical generation and elimination. Meanwhile, this scaffold promoted rat bone marrow stromal cells' osteogenic differentiation and achieved significant ectopic mineralization after 4 weeks of subcutaneous implantation in nude mice. Moreover, after 8 weeks of implantation in the rat critical-sized periodontal bone defect model, CSC-g-nHAp conferred 5.5-fold greater alveolar bone regeneration than the untreated group. This cationic biopolymeric scaffold could regulate the local microenvironment through the synergistic effects of its antibacterial, antioxidant, and osteoconductive activities to promote solid periodontal bone regeneration.

Components and physical properties of hydrogels modulate inflammatory response and cartilage repair.

Collagen and hyaluronic acid are commonly applied in cartilage tissue engineering, yet there has been limited investigation into their inflammatory response, a crucial factor in articular cartilage repair. This study aimed to evaluate the impact of components and physical properties of hydrogels on inflammatory response and cartilage repair. Three kinds of hydrogels with comparable storage moduli at low frequencies were designed and fabricated, namely, methacrylic anhydride-modified hyaluronic acid hydrogel (HAMA), methacrylic anhydride-modified type I collagen hydrogel (CMA) and unmodified type I collagen hydrogel (Col). HAMA hydrogel was unfavorable for adhesion and spreading of BMSCs. Furthermore, HAMA hydrogel stimulated rapid migration and pro-inflammatory M1 polarization of macrophages, leading to persistent and intense inflammation, which was unfavorable for cartilage repair. CMA and Col hydrogels possessed the same component and facilitated the adhesion, spreading and proliferation of BMSCs. Compared with CMA hydrogel, Col hydrogel induced rapid migration and moderate M1 polarization of macrophages at the early stage of injury, which was mainly influenced by its fast dissolution rate, small pore size fiber network structure and rapid stress relaxation. In addition, the phenotype of macrophages timely transformed into anti-inflammatory M2 due to the properties of the collagen component, which shortened the duration of inflammation and enhanced cartilage repair. The results indicated that moderate macrophage activation adjusted by hydrogel components and physical properties was critical in modulating inflammation and cartilage regeneration.

Optimization of exosome-based cell-free strategies to enhance endogenous cell functions in tissue regeneration.

Exosomes, nanoscale extracellular vesicles, play a crucial role in intercellular communication, owing to their biologically active cargoes such as RNAs and proteins. In recent years, they have emerged as a promising tool in the field of tissue regeneration, with the potential to initiate a new trend in cell-free therapy. However, it's worth noting that not all types of exosomes derived from cells are appropriate for tissue repair. Thus, selecting suitable cell sources is critical to ensure their efficacy in specific tissue regeneration processes. Current therapeutic applications of exosomes also encounter several limitations, including low-specific content for targeted diseases, non-tissue-specific targeting, and short retention time due to rapid clearance in vivo. Consequently, this review paper focuses on exosomes from diverse cell sources with functions specific to tissue regeneration. It also highlights the latest engineering strategies developed to overcome the functional limitations of natural exosomes. These strategies encompass the loading of specific therapeutic contents into exosomes, the endowment of tissue-specific targeting capability on the exosome surface, and the incorporation of biomaterials to extend the in vivo retention time of exosomes in a controlled-release manner. Collectively, these innovative approaches aim to synergistically enhance the therapeutic effects of natural exosomes, optimizing exosome-based cell-free strategies to boost endogenous cell functions in tissue regeneration. STATEMENT OF SIGNIFICANCE: Exosome-based cell-free therapy has recently emerged as a promising tool for tissue regeneration. This review highlights the characteristics and functions of exosomes from different sources that can facilitate tissue repair and their contributions to the regeneration process. To address the functional limitations of natural exosomes in therapeutic applications, this review provides an in-depth understanding of the latest engineering strategies. These strategies include optimizing exosomal contents, endowing tissue-specific targeting capability on the exosome surface, and incorporating biomaterials to extend the in vivo retention time of exosomes in a controlled-release manner. This review aims to explore and discuss innovative approaches that can synergistically improve endogenous cell functions in advanced exosome-based cell-free therapies for a broad range of tissue regeneration.

Polyvinyl-alcohol, chitosan and graphene-oxide composed conductive hydrogel for electrically controlled fluorescein sodium transdermal release.

Accurate and controlled release of drug molecules is crucial for transdermal drug delivery. Electricity, as an adjustable parameter, offers the potential for precise and controllable drug delivery. However, challenges exist in selecting the appropriate drug carrier, electrical parameters, and release model to achieve controlled electronic drug release. To overcome these challenges, this study designed a functional hydrogel using polyvinyl alcohol, chitosan, and graphene oxide as components that can conduct electricity, and constructed a drug transdermal release model using fluorescein sodium salt with proper electrical parameters. The results demonstrated that the hydrogel system exhibited low cytotoxicity, good conductivity, and desirable drug delivery characteristics. The study also integrated the effects of drug release and tissue repair promotion under electrical stimulation. Cell growth was enhanced under low voltage direct current pulses, promoting cell migration and the release of VEGF and FGF. Furthermore, the permeability of fluorescein sodium salt in the hydrogel increased with direct current stimulation. These findings suggest that the carbohydrate polymers hydrogel could serve as a drug carrier for controlled release, and electrical stimulation offers new possibilities for functional drug delivery and transdermal therapy.

Icariin-loaded 3D-printed porous Ti6Al4V reconstruction rods for the treatment of necrotic femoral heads.

Avascular necrosis of the femoral head is a prevalent hip joint disease. Due to the damage and destruction of the blood supply of the femoral head, the ischemic necrosis of bone cells and bone marrow leads to the structural changes and the collapse of the femoral head. In this study, an icariin-loaded 3D-printed porous Ti6Al4V reconstruction rod (referred to as reconstruction rod) was prepared by 3D printing technology. The mechanical validity of the reconstruction rod was verified by finite element analysis. Through infilling of mercapto hyaluronic acid hydrogel containing icariin into the porous structure, the loading of icariin was achieved. The biological efficacy of the reconstruction rod was confirmed through in vitro cell experiments, which demonstrated its ability to enhance MC3T3-E1 cell proliferation and facilitate cellular adhesion and spreading. The therapeutic efficacy of the reconstruction rod was validated in vivo through a femoral head necrosis model using animal experiments. The results demonstrated that the reconstruction rod facilitated osteogenesis and neovascularization, leading to effective osseointegration between bone and implant. This study provides innovative strategy for the treatment of early avascular necrosis of the femoral head. STATEMENT OF SIGNIFICANCE: The bioactivity of medical titanium alloy implants plays an important role in bone tissue engineering. This study proposed a medicine and device integrated designed porous Ti6Al4V reconstruction rod for avascular necrosis of the femoral head, whose macroscopic structure was customized by selective laser melting. The bionic porous structure of the reconstruction rod promoted the growth of bone tissue and formed an effective interface integration. Meanwhile, the loaded icariin promoted new bone and vascular regeneration, and increased the bone mass and bone density. Therefore, the implantation of reconstruction rod interfered with the further development of necrosis and provided a positive therapeutic effect. This study provides innovative strategies for the treatment of early avascular necrosis of femoral head.

Nanocomposite hydrogel based on chitosan/laponite for sealing and repairing tracheoesophageal fistula.

Tracheoesophageal fistula (TEF) is an abnormal connection between the trachea and esophagus that severely impairs quality of life. Current treatment options have limitations, including conservative treatment, surgical repair, and esophageal stent implantation. Here, we introduced laponite (LP) nano-clay to improve chitosan-based hydrogels' rheological properties and mechanical properties and developed an endoscopically injectable nanocomposite shear-thinning hydrogel to seal and repair fistulas as an innovative material for the treatment of TEF. Excellent injectability, rheological properties, mechanical strength, self-healing, biodegradability, biocompatibility, and tissue repair characterize the new hydrogel. The introduction of LP nano-clay improves the gel kinetics problem of hydrogels to realize the sol-gel transition immediately after injection, avoiding gel flow to non-target sites. The addition of LA nano-clay can significantly improve the rheological properties and mechanical strength of hydrogels, and hydrogel with LP content of 3 % shows better comprehensive performance. The nanocomposite hydrogel also shows good cytocompatibility and can promote wound repair by promoting the migration of HEEC cells and the secretion of VEGF and FGF. These findings suggest that this nanocomposite hydrogel is a promising biomaterial for TEF treatment.

Efficient Osteogenic Activity of PEEK Surfaces Achieved by Femtosecond Laser-Hydroxylation.

Poly(etheretherketone) (PEEK) is regarded as an attractive orthopedic material because of its good biocompatibility and mechanical properties similar to natural bone. The efficient activation methods for the surfaces of PEEK matrix materials have become a hot research topic. In this study, a method using a femtosecond laser (FSL) followed by hydroxylation was developed to achieve efficient bioactivity. It produces microstructures, amorphous carbon, and grafted -OH groups on the PEEK surface to enhance hydrophilicity and surface energy. Both experimental and simulation results show that our modification leads to a superior ability to induce apatite deposition on the PEEK surface. The results also demonstrate that efficient grafting of C-OH through FSL-hydroxylation can effectively enhance cell proliferation and osteogenic differentiation compared to other modifications, thus improving osteogenic activity. Overall, FSL hydroxylation treatment is proved to be a simple, efficient, and environmentally friendly modification method for PEEK activation. It could expand the applications of PEEK in orthopedics, as well as promote the surface modification and structural design of other polymeric biomaterials to enhance bioactivity.

Hydrophobic Tetracycline Immobilized in Fibrous Hyaluronan Regulates Adhesive Collagen-Based Hydrogel Stability for Infected Wound Healing.

Collagen-based hydrogels have a significant impact on wound healing, but they suffer from structural instability and bacterial invasion in infected wounds. Here, electrospun nanofibers of esterified hyaluronan (HA-Bn/T) are developed to immobilize the hydrophobic antibacterial drug tetracycline by π-π stacking interaction. Dopamine-modified hyaluronan and HA-Bn/T are employed simultaneously to stabilize the structure of collagen-based hydrogel by chemically interweaving the collagen fibril network and decreasing the rate of collagen degradation. This renders it injectable for in situ gelation, with suitable skin adhesion properties and long-lasting drug release capability. This hybridized interwoven hydrogel promotes the proliferation and migration of L929 cells and vascularization in vitro. It presents satisfactory antibacterial ability against Staphylococcus aureus and Escherichia coli. The structure also retains the functional protein environment provided by collagen fiber, inhibits the bacterial environment of infected wounds, and modulates local inflammation, resulting in neovascularization, collagen deposition, and partial follicular regeneration. This strategy offers a new solution for infected wound healing.