Nanofiber Aerogels with Precision Macrochannels and LL-37-Mimic Peptides Synergistically Promote Diabetic Wound Healing.

Fast healing of diabetic wounds remains a major clinical challenge. Herein, this work reports a strategy to combine nanofiber aerogels containing precision macrochannels and the LL-37-mimic peptide W379 for rapid diabetic wound healing. Nanofiber aerogels consisting of poly(glycolide-co-lactide) (PGLA 90:10)/gelatin and poly-p-dioxanone (PDO)/gelatin short electrospun fiber segments were prepared by partially anisotropic freeze-drying, crosslinking, and sacrificial templating with three-dimensional (3D)-printed meshes, exhibiting nanofibrous architecture and precision micro-/macrochannels. Like human cathelicidin LL-37, W379 peptide at a concentration of 3 µg/mL enhanced the migration and proliferation of keratinocytes and dermal fibroblasts in a cell scratch assay and a proliferation assay. In vivo studies show that nanofiber aerogels with precision macrochannels can greatly promote cell penetration compared to aerogels without macrochannels. Relative to control and aerogels with and without macrochannels, adding W379 peptides to aerogels with precision macrochannels shows the best efficacy in healing diabetic wounds in mice in terms of cell infiltration, neovascularization, and re-epithelialization. The fast re-epithelization could be due to upregulation of phospho-extracellular signal-regulated kinase (p38 MAPK) after treatment with W379. Together, the approach developed in this work could be promising for the treatment of diabetic wounds and other chronic wounds.

Ultra-absorptive Nanofiber Swabs for Improved Collection and Test Sensitivity of SARS-CoV-2 and other Biological Specimens.

Following the COVID-19 outbreak, swabs for biological specimen collection were thrust to the forefront of healthcare materials. Swab sample collection and recovery are vital for reducing false negative diagnostic tests, early detection of pathogens, and harvesting DNA from limited biological samples. In this study, we report a new class of nanofiber swabs tipped with hierarchical 3D nanofiber objects produced by expanding electrospun membranes with a solids-of-revolution-inspired gas foaming technique. Nanofiber swabs significantly improve absorption and release of proteins, cells, bacteria, DNA, and viruses from solutions and surfaces. Implementation of nanofiber swabs in SARS-CoV-2 detection reduces the false negative rates at two viral concentrations and identifies SARS-CoV-2 at a 10× lower viral concentration compared to flocked and cotton swabs. The nanofiber swabs show great promise in improving test sensitivity, potentially leading to timely and accurate diagnosis of many diseases.

3D Hybrid Nanofiber Aerogels Combining with Nanoparticles Made of a Biocleavable and Targeting Polycation and MiR-26a for Bone Repair.

The healing of large bone defects represents a clinical challenge, often requiring some form of grafting. Three-dimensional (3D) nanofiber aerogels could be a promising bone graft due to their biomimetic morphology and controlled porous structures and composition. miR-26a has been reported to induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and facilitate bone formation. Introducing miR-26a with a suitable polymeric vector targeting BMSCs could improve and enhance the functions of 3D nanofiber aerogels for bone regeneration. Herein, we first developed the comb-shaped polycation (HA-SS-PGEA) carrying a targeting component, biocleavable groups and short ethanolamine (EA)-decorated poly(glycidyl methacrylate) (PGMA) (abbreviated as PGEA) arms as miR-26a delivery vector. We then assessed the cytotoxicity and transfection efficiency of this polycation and cellular response to miR-26a-incorporated nanoparticles (NPs) in vitro. HA-SS-PGEA exhibited a stronger ability to transport miR-26a and exert its functions than the gold standard polyethyleneimine (PEI) and low-molecular-weight linear PGEA. We finally examined the efficacy of HA-SS-PGEA/miR-26a NPs loaded 3D hybrid nanofiber aerogels showing a positive effect on the cranial bone defect healing. Together, the combination of 3D nanofiber aerogels and functional NPs consisting of a biodegradable and targeting polycation and therapeutic miRNA could be a promising approach for bone regeneration.

Engineering Biomimetic Nanofiber Microspheres with Tailored Size, Predesigned Structure, and Desired Composition via Gas Bubble-Mediated Coaxial Electrospray.

Minimally invasive therapies avoiding surgical complexities evoke great interest in developing injectable biomedical devices. Herein, a versatile approach is reported for engineering injectable and biomimetic nanofiber microspheres (NMs) with tunable sizes, predesigned structures, and desired compositions via gas bubble-mediated coaxial electrospraying. The sizes and structures of NMs are controlled by adjusting processing parameters including air flow rate, applied voltage, distance, and spinneret configuration in the coaxial setup. Importantly, unlike the self-assembly method, this technique can be used to fabricate NMs from any material feasible for electrospinning or other nanofiber fabrication techniques. To demonstrate the versatility, open porous NMs are successfully fabricated that consist of various short nanofibers made of poly(ε-caprolactone), poly(lactic-co-glycolic acid), gelatin, methacrylated gelatin, bioglass, and magneto-responsive polymer composites. Open porous NMs support human neural progenitor cell growth in 3D with a larger number and more neurites than nonporous NMs. Additionally, highly open porous NMs show faster cell infiltration and host tissue integration than nonporous NMs after subcutaneous injection to rats. Such a novel class of NMs holds great potential for many biomedical applications such as tissue filling, cell and drug delivery, and minimally invasive tissue regeneration.

Tethering peptides onto biomimetic and injectable nanofiber microspheres to direct cellular response.

Biomimetic and injectable nanofiber microspheres (NMs) could be ideal candidate for minimally invasive tissue repair. Herein, we report a facile approach to fabricate peptide-tethered NMs by combining electrospinning, electrospraying, and surface conjugation techniques. The composition and size of NMs can be tuned by varying the processing parameters during the fabrication. Further, bone morphogenic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) mimicking peptides have been successfully tethered onto poly(ε-caprolactone) (PCL):gelatin:(gelatin-methacryloyl) (GelMA)(1:0.5:0.5) NMs through photocrosslinking of the methacrylic group in GelMA and octenyl alanine (OCTAL) in the modified peptides. The BMP-2-OCTAL peptide-tethered NMs significantly promote osteogenic differentiation of bone marrow-derived stem cells (BMSCs). Moreover, human umbilical vein endothelial cells (HUVECs) seeded on VEGF mimicking peptide QK-OCTAL-tethered NMs significantly up-regulated vascular-specific proteins, leading to microvascularization. The strategy developed in this work holds great potential in developing a biomimetic and injectable carrier to efficiently direct cellular response (Osteogenesis and Angiogenesis) for tissue repair.

Pharmacological Evaluation of Selected Medicinal Plants Used in the Management of Oral and Skin Infections in Ebem-Ohafia District, Abia State, Nigeria.

Oral and skin infections contribute significantly to the global health challenges responsible for the current trend of increased morbidity and premature death. The purpose of this study was to document medicinal plants used in the management of oral and skin infections in Ebem-Ohafia Local Government Area (LGA), Abia State, and to characterize the in vitro antioxidant and antibacterial activity. The thin layer chromatography (TLC) profiling of ten of the selected folklore medicine was carried out using a various solvent system of different polarity index. The antioxidant capacity of the plant extracts was evaluated using chemical-based methods, and its antibacterial effect was investigated using disc diffusion and microdilution methods. Sixty-one plant species belonging to 26 families were discovered, and the most frequently cited species are Euphorbiaceae (18.03%), Fabaceae (11.47%), and Asteraceae (11.47%). All the plant extracts showed a promising free radical scavenging activity and efficient ferric reducing antioxidant power in a concentration-dependent manner possibly due to their richness in polyphenol with TLC profiling showing maximum three bands of phytochemicals. Also, the plant extracts exhibited a mild to weak antibacterial activity against our panel of bacterial strains having MIC values ranging from 256 to > 512 µg/ mL reflected in their zone of inhibition at 10 µg/disc. The data obtained for Breynia nivosa (BN), Eleusine indica (EI), Cassia alata (CA), Chromolaena odorata (CO), and Acalypha hispida (AH) extracts substantiate the traditional use of these herbal remedies in the region and open the possibility for the development of cheaper and affordable drugs in the treatment of oral and skin infections. Further studies are needed to identify active ingredient with strong antibacterial and antioxidant capacities along with their molecular mechanisms.

Inflammatory proteins in nasal lavage of workers exposed to occupational agents.

BACKGROUND: Low-molecular-weight (LMW) and high-molecular-weight (HMW) agents have been recognized as causes of occupational rhinitis (OR). Immunological mechanisms underlying OR differ according to the type of exposure. While HMW agents act mainly through IgE-mediated mechanisms, LMW agents appear to act through both immunological and non-immunological mechanisms. OBJECTIVE: The objective of this study was to identify potential differences in the upper airways inflammatory response after exposure to LMW and HMW agents by specific inhalation challenge test (SIC). METHODS: Nasal lavage (NL) samples from 20 subjects who were exposed to HMW (n = 10, Group I) and LMW (n = 10, Group II) at their workplaces were collected after SIC with control and specific occupational agents. These samples were analysed for 47 inflammatory markers using multiplex bead technology. RESULTS: After exposure to specific agent, Group I exhibited higher concentrations of the following proteins compared to Group II: fibrinogen (median (interquartile range) Group I: 0.09 (0.00) µg/mL, Group II: 0.04 (0.05) µg/mL, P = .05); haptoglobin (Group I: 0.86 (0.01) µg/mL, Group II: 0.14 (0.20) µg/mL, P = .02); vascular cell adhesion molecule-1 (VCAM-1) (Group I: 0.34 (0.67) ng/mL, Group II: 0.11 (0.11) ng/mL, P = .01); vascular endothelial growth factor (VEGF) (Group I: 157.0 (154.0) pg/mL, Group II: 98.0 (20.25) pg/mL, P = .01); and vitamin D (VDBP) (Group I: 0.06 (0.13) µg/mL, Group II: 0.03 (0.03) µg/mL, P = .04). No statistically significant differences in proteins profiles were observed between the groups after exposure to control agent. Also, subjects exposed to HMW agents showed a significant increase in NL levels of C-reactive protein compared to control-day exposure. CONCLUSIONS AND CLINICAL RELEVANCE: Exposure to HMW and LMW agents by SIC induced a differential nasal airway response including acute-phase reactants proteins (fibrinogen, haptoglobin and CRP), cell adhesion molecules (VCAM-1), endothelial growth factors (VEGF) and VDBP.

Dual Stimuli-Responsive Vesicular Nanospheres Fabricated by Lipopolymer Hybrids for Tumor-Targeted Photodynamic Therapy.

Smart delivery system of photosensitizer chlorin e6 (Ce6) has been developed for targeted photodynamic therapy (PDT). Simple self-assemblies of the mixtures comprising soybean lecithin derived phosphatidylcholine (PC), phosphatidylethanolamine-poly(L-histidine)40 (PE-p(His)40), and folic acid (FA) conjugated phosphatidylethanolamine-poly(N-isopropylacrylamide)40 (PE-p(NIPAM)40-FA) in different ratios yield smart nanospheres characterized by (i) stable and uniform particle size (∼100 nm), (ii) positive surface charge, (iii) high hydrophobic drug (Ce6) loading efficiency up to 45%, (iv) covalently linked targeting moiety, (v) low cytotoxicity, and (vi) smartness showing p(His) block oriented pH and p(NIPAM) oriented temperature responsiveness. The Ce6-encapsulated vesicular nanospheres (Ce6@VNS) were used to confirm the efficiency of cellular uptake, intracellular distribution, and phototoxicity against KB tumor cells compared to free Ce6 at different temperature and pH conditions. The Ce6@VNS system showed significant photodynamic therapeutic efficiency on KB cells than free Ce6. A receptor-mediated inhibition study proved the site-specific delivery of Ce6 in targeted tumor cells.

TOX expression and role in CTCL.

BACKGROUND: Cutaneous T-cell lymphomas (CTCL) are skin malignancies including mycosis fungoides (MF) and CD30(+) lymphoproliferative disorders (LPD). In early disease, CTCL can be difficult to diagnose, especially in MF for which there is no reliable diagnostic marker. MF/CTCL have increased expression of thymocyte selection-associated HMG box protein (TOX). Although TOX has been proposed to be a diagnostic marker for MF, further validation studies are needed. Moreover, it is unclear what drives TOX expression or its role in MF/CTCL. OBJECTIVE: We hypothesize evaluation of TOX levels across a spectrum of CTCL, including MF precursor (large plaque parapsoriasis, LPP), will help elucidate the implications of altered TOX expression. MATERIALS AND METHODS: TOX staining was performed in MF, CD30(+) LPD, LPP as well as benign inflammatory dermatoses (BID) and normal skin (NS). CTCL cell lines were utilized to evaluate the regulation of TOX. RESULTS: Positive TOX expression was identified in 73.6% of MF cases and in 31.6% of BID/NS. TOX had a positive predictive value (PPV) for MF of 86.7% and a negative predictive value (NPV) of 48.1%. TOX expression in MF was detected more commonly in Black patients (P = 0.015) and less commonly in transformed MF (P = 0.045). LPP had positive TOX staining in 70.0%. In CTCL cells, GATA3 knockdown decreased TOX mRNA and protein expression. TOX expression also decreased in the presence of CTCL therapeutics. CONCLUSION: Our data indicate that TOX is useful as a diagnostic marker in MF. Moreover, TOX expression was evident in LPP, indicating it may have a previously unappreciated role in the development of MF. Finally, our data suggest that GATA3 regulates TOX, revealing insight into TOX regulation.

Loss of anterior cruciate ligament integrity and the development of radiographic knee osteoarthritis: a sub-study of the osteoarthritis initiative.

INTRODUCTION: The aim of this study was to determine whether loss of ACL integrity in an older cohort precedes the onset of radiographic OA (ROA). METHODS: Participants in this nested case-control study were selected from the Osteoarthritis Initiative (OAI) study who had risk factors for OA development but did not have ROA (Kellgren-Lawrence grading (KLG) of 0 or 1) in both knees at baseline. The MRIs were assessed for the presence of ACL tears. Case knees were defined by the development of ROA on knee radiographs between the 12 and 48 month visits. Their radiographs were assessed at P0 (time of onset of radiographic knee OA), 1 year prior to P0 (P-1) and at baseline. Controls were selected from amongst those who did not develop incident ROA and were matched to cases. RESULTS: 355 persons who developed ROA were matched to 355 controls. No relationship between loss of ACL integrity and incident ROA was found at any assessment time point. Odds ratios (OR) for baseline, 1 year prior to incident ROA (P1) and at point of occurrence of incident ROA (P0) were 2.00 (0.66-6.06), 2.5 (0.76-8.24) and 2.75 (0.85-8.88) respectively. A significant risk of incident ROA was found in participants who had a history of knee injury with an OR of 1.51 (1.05-2.16). CONCLUSION: Loss of ACL integrity does not confer a significantly increased risk of incident ROA in an older adult cohort. In contrast, a history of knee injury was associated with an increased risk of incident ROA.

Lipo-poly(L-histidine) hybrid materials with pH-sensitivity, intracellular delivery efficiency, and intrinsic targetability to cancer cells.

Biocompatible lipo-histidine hybrid materials conjugated with IR820 dye show pH-sensitivity, efficient intracellular delivery of doxorubicin (Dox), and intrinsic targetability to cancer cells. These new materials form highly uniform Dox-loaded nanosized vesicles via a self-assembly process showing good stability under physiological conditions. The Dox-loaded micelles are effective for suppressing MCF-7 tumors, as demonstrated in vitro and in vivo. The combined mechanisms of the EPR effect, active internalization, endosomal-triggered release, and drug escape from endosomes, and a long blood circulation time, clearly prove that the IR820 lipopeptide DDS is a safe theranostic agent for imaging-guided cancer therapy.

Genetic markers associated with progression in early mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is a rare, but potentially devastating malignancy. It classically presents with cutaneous patches and plaques and can progress to tumours on the skin with lymph node, blood and visceral involvement. While most patients with MF have a relatively benign disease course, a subset of patients will develop progressive disease that is often fatal. OBJECTIVE: The aim of this study was to identify genetic markers in early MF limited to the skin (stages IA-IIA) that distinguish those patients who will have progressive disease from those who will not, so that early appropriate treatment may be instituted. METHODS: The study includes 18 patients who were diagnosed with early stage MF at the time of biopsy and had follow-up to determine which patients developed progressive disease. RNA was extracted from skin biopsy specimens and analysed for expression of CD3, FOXP3, IFNγ, Interleukin (IL)-4, IL-13, KIR3DL2, MICB, PLS3 and STAT4 by quantitative real-time polymerase chain reaction. RESULTS/CONCLUSIONS: Reduced expression of FOXP3 and STAT4 and increased expression of IL-4 relative to CD3 expression levels were significantly associated with MF progression. Further studies will be needed to fully assess the usefulness of these genetic markers to predict disease progression and guide treatment options in patients diagnosed with early MF.

Current and Future Directions in Fluorescence Imaging-Guided Debridement.

Significance: Sterility and reduction of the bioburden are crucial for healing in chronic wounds such as diabetic foot ulcers. Although there are methods for measuring bioburdens, such as semiquantitative analysis of swab/biopsy samples, microbiological sampling, and molecular diagnostics, these tools are less accessible owing to costs or not being as quick as other methods. These methods are also dependent on clinical assessment by the clinician, and high bacterial burden may appear asymptomatic. Recent Advances: Autofluorescence (AF) imaging is a novel technology for identifying and quantifying chronic inhibitory bacterial load in chronic wounds. Eighty-seven percent of bacteria that frequent chronic wounds have fluorophores that fluoresce under violet light as red or cyan, depending on the type of fluorophore. Therefore, AF image-guided treatment is becoming increasingly effective for physicians to implement wound dressing changes and debridement because bacterial burdens are difficult to locate clinically. Critical Issue: Products such as the commercially available MolecuLight i:X and MolecuLight DX function as handheld cameras for physicians to use as a reference but require additional work to ensure that the photograph will be taken with adequate lighting. Future Directions: Designs for Vision Inc. introduced a device called REVEAL, an AF imaging form factor that allows the device to be worn on top of a pair of glasses, which the physician would wear intraoperatively. The benefits of this form factor include not requiring certain lighting conditions and not having to interpret the results using a handheld camera, allowing the device to be used during active surgical debridement.

New dimensions of electrospun nanofiber material designs for biotechnological uses.

Electrospinning technology has garnered wide attention over the past few decades in various biomedical applications including drug delivery, cell therapy, and tissue engineering. This technology can create nanofibers with tunable fiber diameters and functionalities. However, the 2D membrane nature of the nanofibers, as well as the rigidity and low porosity of electrospun fibers, lower their efficacy in tissue repair and regeneration. Recently, new avenues have been explored to resolve the challenges associated with 2D electrospun nanofiber membranes. This review discusses recent trends in creating different electrospun nanofiber microstructures from 2D nanofiber membranes by using various post-processing methods, as well as their biotechnological applications.

Development of bioactive short fiber-reinforced printable hydrogels with tunable mechanical and osteogenic properties for bone repair.

Personalized bone-regenerative materials have attracted substantial interest in recent years. Modern clinical settings demand the use of engineered materials incorporating patient-derived cells, cytokines, antibodies, and biomarkers to enhance the process of regeneration. In this work, we formulated short microfiber-reinforced hydrogels with platelet-rich fibrin (PRF) to engineer implantable multi-material core-shell bone grafts. By employing 3D bioprinting technology, we fabricated a core-shell bone graft from a hybrid composite hydroxyapatite-coated poly(lactic acid) (PLA) fiber-reinforced methacryolyl gelatin (GelMA)/alginate hydrogel. The overall concept involves 3D bioprinting of long bone mimic microstructures that resemble a core-shell cancellous-cortical structure, with a stiffer shell and a softer core with our engineered biomaterial. We observed a significantly enhanced stiffness in the hydrogel scaffold incorporated with hydroxyapatite (HA)-coated PLA microfibers compared to the pristine hydrogel construct. Furthermore, HA non-coated PLA microfibers were mixed with PRF and GelMA/alginate hydrogel to introduce a slow release of growth factors which can further enhance cell maturation and differentiation. These patient-specific bone grafts deliver cytokines and growth factors with distinct spatiotemporal release profiles to enhance tissue regeneration. The biocompatible and bio-responsive bone mimetic core-shell multi-material structures enhance osteogenesis and can be customized to have materials at a specific location, geometry, and material combination.

Anti-Inflammatory Peptide-Conjugated Silk Fibroin/Cryogel Hybrid Dual Fiber Scaffold with Hierarchical Structure Promotes Healing of Chronic Wounds.

Chronic wounds resulting from diabetes, pressure, radiation therapy, and other factors continue to pose significant challenges in wound healing. To address this, this study introduces a novel hybrid fibroin fibrous scaffold (FFS) comprising randomly arranged fibroin fibers and vertically aligned cryogel fibers (CFs). The fibroin scaffold is efficiently degummed at room temperature and simultaneously formed a porous structure. The aligned CFs are produced via directional freeze-drying, achieved by controlling solution concentration and freezing polymerization temperature. The incorporation of aligned CFs into the expanded fibroin fiber scaffold leads to enhanced cell infiltration both in vitro and in vivo, further elevating the hybrid scaffold's tissue compatibility. The anti-inflammatory peptide 1 (AP-1) is also conjugated to the hybrid fibrous scaffold, effectively transforming the inflammatory status of chronic wounds from pro-inflammatory to pro-reparative. Consequently, the FFS-AP1+CF group demonstrates superior granulation tissue formation, angiogenesis, collagen deposition, and re-epithelialization during the proliferative phase compared to the commercial product PELNAC. Moreover, the FFS-AP1+CF group displays epidermis thickness, number of regenerated hair follicles, and collagen density closer to normal skin tissue. These findings highlight the potential of random fibroin fibers/aligned CFs hybrid fibrous scaffold as a promising approach for skin tissue filling and tissue regeneration.

Decellularized extracellular matrix-decorated 3D nanofiber scaffolds enhance cellular responses and tissue regeneration.

The use of decellularized extracellular matrix products in tissue regeneration is quite alluring yet practically challenging due to the limitations of its availability, harsh processing techniques, and host rejection. Scaffolds obtained by either incorporating extracellular matrix (ECM) material or coating the surface can resolve these challenges to some extent. However, these scaffolds lack the complex 3D network formed by proteins and growth factors observed in natural ECM. This study introduces an approach utilizing 3D nanofiber scaffolds decorated with dECM to enhance cellular responses and promote tissue regeneration. Notably, the dECM can be customized according to specific cellular requirements, offering a tailored environment for enhanced therapeutic outcomes. Two types of 3D expanded scaffolds, namely radially aligned scaffolds (RAS) and laterally expanded scaffolds (LES) fabricated by the gas-foaming expansion were utilized. To demonstrate the proof-of-concept, human dermal fibroblasts (HDFs) seeded on these scaffolds for up to 8 weeks, resulted in uniform and highly aligned cells which deposited ECM on the scaffolds. These cellular components were then removed from the scaffolds through decellularization (e.g., SDS treatment and freeze-thaw cycles). The dECM-decorated 3D expanded nanofiber scaffolds can direct and support cell alignment and proliferation along the underlying fibers upon recellularization. An in vitro inflammation assay indicates that dECM-decorated LES induces a lower immune response than dECM-decorated RAS. Further, subcutaneous implantation of dECM-decorated RAS and LES shows higher cell infiltration and angiogenesis within 7 and 14 days than RAS and LES without dECM decoration. Taken together, dECM-decorated 3D expanded nanofiber scaffolds hold great potential in tissue regeneration and tissue modeling. STATEMENT OF SIGNIFICANCE: Decellularized ECM scaffolds have attained widespread attention in biomedical applications due to their intricate 3D framework of proteins and growth factors. Mimicking such a complicated architecture is a clinical challenge. In this study, we developed natural ECM-decorated 3D electrospun nanofiber scaffolds with controlled alignments to mimic human tissue. Fibroblasts were cultured on these scaffolds for 8 weeks to deposit natural ECM and decellularized by either freeze-thawing or detergent to obtain decellularized ECM scaffolds. These scaffolds were tested in both in-vitro and in-vivo conditions. They displayed higher cellular attributes with lower immune response making them a good grafting tool in tissue regeneration.

Mechanically resilient hybrid aerogels containing fibers of dual-scale sizes and knotty networks for tissue regeneration.

The structure and design flexibility of aerogels make them promising for soft tissue engineering, though they tend to come with brittleness and low elasticity. While increasing crosslinking density may improve mechanics, it also imparts brittleness. In soft tissue engineering, resilience against mechanical loads from mobile tissues is paramount. We report a hybrid aerogel that consists of self-reinforcing networks of micro- and nanofibers. Nanofiber segments physically entangle microfiber pillars, allowing efficient stress distribution through the intertwined fiber networks. We show that optimized hybrid aerogels have high specific tensile moduli (~1961.3 MPa cm3 g-1) and fracture energies (~7448.8 J m-2), while exhibiting super-elastic properties with rapid shape recovery (~1.8 s). We demonstrate that these aerogels induce rapid tissue ingrowth, extracellular matrix deposition, and neovascularization after subcutaneous implants in rats. Furthermore, we can apply them for engineering soft tissues via minimally invasive procedures, and hybrid aerogels can extend their versatility to become magnetically responsive or electrically conductive, enabling pressure sensing and actuation.

Copper-Cystine Biohybrid-Embedded Nanofiber Aerogels Show Antibacterial and Angiogenic Properties.

Copper-cystine-based high aspect ratio structures (CuHARS) possess exceptional physical and chemical properties and exhibit remarkable biodegradability in human physiological conditions. Extensive testing has confirmed the biocompatibility and biodegradability of CuHARS under diverse biological conditions, making them a viable source of essential Cu2+. These ions are vital for catalyzing the production of nitric oxide (NO) from the decomposition of S-nitrosothiols (RSNOs) found in human blood. The ability of CuHARS to act as a Cu2+ donor under specific concentrations has been demonstrated in this study, resulting in the generation of elevated levels of NO. Consequently, this dual function makes CuHARS effective as both a bactericidal agent and a promoter of angiogenesis. In vitro experiments have shown that CuHARS actively promotes the migration and formation of complete lumens by redirecting microvascular endothelial cells. To maximize the benefits of CuHARS, they have been incorporated into biomimetic electrospun poly(ε-caprolactone)/gelatin nanofiber aerogels. Through the regulated release of Cu2+ and NO production, these channeled aerogels not only provide antibacterial support but also promote angiogenesis. Taken together, the inclusion of CuHARS in biomimetic scaffolds could hold great promise in revolutionizing tissue regeneration and wound healing.

Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury.

OBJECTIVE: Post-traumatic osteoarthritis (PTOA) occurs after anterior cruciate ligament (ACL) injury. PTOA may be initiated by early expression of proteolytic enzymes capable of causing degradation of the articular cartilage at time of injury. This study investigated the production of three of these key proteases in multiple joint tissues after ACL injury and subsequent markers of cartilage turnover. METHODS: ACL transection was performed in adolescent minipigs. Collagenase (MMP-1 and MMP-13) and aggrecanase (ADAMTS-4) gene expression changes were quantified in the articular cartilage, synovium, injured ligament, and the provisional scaffold at days 1, 5, 9, and 14 post-injury. Markers of collagen degradation (C2C), synthesis (CPII) and aggrecan synthesis (CS 846) were quantified in the serum and synovial fluid. Histologic assessment of the cartilage integrity (OARSI scoring) was also performed. RESULTS: MMP-1 gene expression was upregulated in the articular cartilage, synovium and ligament after ACL injury. MMP-13 expression was suppressed in the articular cartilage, but upregulated 100-fold in the synovium and ligament. ADAMTS-4 was upregulated in the synovium and ligament but not in the articular cartilage. The concentration of collagen degradation fragments (C2C) in the synovial joint fluid nearly doubled in the first five days after injury. CONCLUSION: We conclude that upregulation of genes coding for proteins capable of degrading cartilage ECM is seen within the first few days after ACL injury, and this response is seen not only in chondrocytes, but also in cells in the synovium, ligament and provisional scaffold.