The fabrication of biomineralized fiber-aligned PLGA scaffolds and their effect on enhancing osteogenic differentiation of UCMSC cells.

The key factor of scaffold design for bone tissue engineering is to mimic the microenvironment of natural bone extracellular matrix (ECM) and guide cell osteogenic differentiation. The biomineralized fiber-aligned PLGA scaffolds (a-PLGA/CaPs) was developed in this study by mimicking the structure and composition of native bone ECM. The aligned PLGA fibers was prepared by wet spinning and then biomineralized via an alternate immersion method. Introduction of a bioceramic component CaP onto the PLGA fibers led to changes in surface roughness and hydrophilicity, which showed to modulate cell adhesion and cell morphology of umbilical cord mesenchymal stem cells (UCMSCs). It was found that organized actin filaments of UCMSCs cultured on both a-PLGA and a-PLGA/CaP scaffolds appeared to follow contact guidance along the aligned fibers, and those cells grown on a-PLGA/CaP scaffolds exhibited a more polarized cellular morphology. The a-PLGA/CaP scaffold with multicycles of mineralization facilitated the cell attachment on the fiber surfaces and then supported better cell adhesion and contact guidance, leading to enhancement in following proliferation and osteogenic differentiation of UCMSCs. Our results give some insights into the regulation of cell behaviors through design of ECM-mimicking structure and composition and provide an alternative wet-spun fiber-aligned scaffold with HA-mineralized layer for bone tissue engineering application.

Wearable electrochemical glucose sensor of high flexibility and sensitivity using novel mushroom-like gold nanowires decorated bendable stainless steel wire sieve.

Long-term high blood glucose levels brings extremely detrimental effect on diabetic patients, such as blindness, renal failure, and cardiovascular diseases. Therefore, there is an urgent need to develop highly flexible and sensitive sensors for precisely non-invasive and continuous monitoring glucose levels. Herein, we present a highly flexible and sensitive wearable sensor for non-enzymatic electrochemical glucose analysis with vertically aligned mushroom-like gold nanowires (v-AuNWs) chemically grown on stainless steel wire sieve (SSWS) as integrated electrode. Owing to the unique nanostructures and excellent catalysis of the v-AuNWs, the as-fabricated glucose sensors exhibit superior flexibility and excellent electro-catalytic capability. In detail, these sensors display rapid response towards glucose within 5 s, and the sensor constructed with v-AuNWs for growth time of 15 min shows the highest sensitivity of 180.1 µA mM-1 cm-2 within a wide linear range of 6.5 × 10-4 mM-12.0 mM and the lowest detection limit of 0.65 µM (S/N = 3). It is noteworthy that due to the good ductility of the v-AuNWs and their strong contact with the SSWS substrate, these glucose sensors exhibit no obvious response variation after repeated bending for 100 times at bending angle of 180°. Additionally, the glucose sensors display superior anti-interfering capability as well as desirable repeatability. More importantly, these glucose sensors can be attached on human skin to determine sweat glucose reliably and analyze glucose concentration in human serum in vitro.

Effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen for diabetic foot ulcers.

Diabetic foot ulcers were a significant complication of diabetes and were accompanied by delayed wound healing. To compare the effect of topical application electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) dressing with alginate dressing when treating diabetic foot ulcers (DFUs). A single-center, prospective, randomized, patient-blinded clinical trial was conducted from July 1, 2023, to December 26, 2023. The clinical trial registration was completed on August 28, 2023 (ClinicalTrials.gov Identifier: NCT06014437). The eligible patients with DFUs of 1-20 cm2 present for at least 1 month and with Wagner grade 1 or 2. They were randomized 1:1 to receive PLCL/Fg or alginate dressing. Participants received PLCL/Fg dressing 1-3 times per week or alginate dressing 3 times per week for 12 weeks. A total of 52 patients (33 men [63.5 %]; mean [SD] age, 63.1 [11.9] years; mean [SD] diabetes time, 8.3 [4.6] years) with DFUs were assessed for this study. The DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 3.8 [3.2] cm2) were randomized to receive either the PLCL/Fg dressing (n = 26) or the alginate dressing (n = 26) for as long as 12 weeks. In this study, the incidence of complete healing included 22 patients (91.7 %) in the PLCL/Fg group and 14 (63.6 %) in the alginate group during the 12-week treatment period (P = 0.003). The treatment-related adverse events that occurred were 5 (20.8 %) in the PLCL/Fg group and 4 (18.1 %) in the comparator group. In this randomized clinical trial, PLCL/Fg dressing showed beneficial effects in DFUs treatment of wound surface reduction and regulating the wound microenvironment.

Silver doped-silica nanoparticles reinforced poly (ethylene glycol) diacrylate/hyaluronic acid hydrogel dressings for synergistically accelerating bacterial-infected wound healing.

Various cutaneous wounds are easily infected with external bacteria, which might result in a chronic wound and ongoing consequences. However, the appropriate development of biomaterials for the controllable delivery of antibacterial silver (Ag) and the simultaneous enhancement of mechanical adhesiveness remains an urgent challenge. Herein, we proposed a double network (DN) hydrogel dressings based on a covalent network of polyethylene glycol diacrylate (PEGDA) and a coordination network between catechol-modified hyaluronic acid (C-HA) and Ag-doped mesoporous silica nanoparticle (AMSN) for promoting the bacterial-infected full-thickness skin wound regeneration. This distinctive dual cross-linked structure of PEGDA/C-HA-AMSN significantly improved physicochemical properties, including gelation time, mechanical performance, and tissue adhesion strength. Importantly, PEGDA/C-HA-AMSN served as a hydrogel dressing that can respond to the acidic environment of bacterial-infected wounds leading to the controllable and optimized delivery of Ag, enabling the durable antibacterial activity accompanied by favorable cytocompatibility and angiogenesis capability. Further in vivo studies validated the higher efficacy of hydrogel dressings in treating wound healing by the synergistic antibacterial, anti-inflammatory, and pro-vascular strategies, meaning the prominent potential of the prepared dressings for overcoming the concerns of wound theranostics.

Preclinical animal study of electrospun poly (l-lactide-co-caprolactone) and formulated porcine fibrinogen for full-thickness diabetic wound regeneration.

Diabetic foot ulcer is one of the most serious chronic complications of diabetes mellitus. It may lead to amputation of the lower extremities for diabetics. Our study was to evaluate the effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) wound dressing on animal wound model. A blend ratio of PLCL/Fg scaffold was 4 (PLCL):1 (Fg). The scanning electron microscopy findings showed that the fibers' diameter was 122.5 ± 80.3 nm, and the tensile strength was 9.2 ± 0.2 MPa. In-vivo study of the hog normal model demonstrated that PLCL/Fg dressing had better biocompatibility, degradability, and ability to restore the skin's normal structure. We evaluated the wound healing processes in the rat diabetic model by macroscopic observation and histological observation at 1, 2, and 3 post-operation weeks. In our study, the PLCL/Fg group performed better 3 weeks after surgery, in terms of macroscopic healing and scarring. After surgery, the PLCL/Fg group showed better fibroblast accumulation, tissue granulation, and collagen expression than the control group. Topical treatment with PLCL/Fg dressing effectively enhanced wound healing in both normal and hyperglycemic conditions, suggesting that it may possess wound-healing potential.

Fabrication and properties of interweaved poly(ether ether ketone) composite scaffolds.

This paper interweaved scaffolds with poly(ether ether ketone) (PEEK) and poly(lactic acid)/Walnut shell/hydroxypatite (PLA/WS/HA) composites by using fused filament fabrication technology, although there was a huge difference in thermal property term between PLA and PEEK. In order to keep mechanical properties of PEEK scaffold and remedy the stress loss produced by pores, PLA/WS/HA composites were used to fill the pores with gradient form outside-in (0.4-0.8 mm, 0.6-1.0 mm, 0.8-1.2 mm and 1.6-2.0 mm). The thermal stability, tensile and compression properties, tensile fracture surface morphology, cytotoxicity and in vivo experiment were investigated. The results showed: the scaffolds were intact without any flashes and surface destruction, and kept a well thermal stability. Compared with the PEEK porous scaffolds, the tensile fracture stress and strain, compression yield stress and strain of interweaved scaffolds were dramatically enhanced by 24.1%, 438%, 359.1% and 921.2%, respectively, and they climbed to the climax at 8 wt% of WS. In vivo experiment showed that the degradation of PLA/WS/HA composites synchronized with the adhesion, proliferation and ingrowth of bone cells, keeping the stable biomechanical properties of interweaved scaffolds. Those experiments showed that interweaved PEEK-PLA/WS/HA scaffolds had the potential to be used as bone implant in tissue engineering.

Halloysites modified polyethylene glycol diacrylate/thiolated chitosan double network hydrogel combined with BMP-2 for rat skull regeneration.

Hydrogel serve as bone tissue engineering have lately received great attention for their good biocompatibility and structures similar to natural extracellular matrices. However, a single component polymer hydrogel is generally detrimental to cell adhesion due to the weaker mechanical properties, which limits their application considerably. In an effort to overcome this disadvantage, we adopt an unconventional dual network hydrogels consisting of the polyethylene glycol diacrylate (PEGDA) covalent network, a thiolated chitosan (TCS) ion crosslinking network and thiolated halloysites (T-HNTs) as reinforcing filler. In addition, bone morphogenetic protein-2 (BMP-2) was loaded into the prepared dual network (DN) hydrogel to improve the bone regeneration function of the DN hydrogel. The resulting PEGDA/TCS/T-HNTs hydrogels showed favourable mechanical property, higher crosslinking density, the lower swelling degree, excellent biocompatibility and cell adhesion ability. The histomorphometric and immunohistochemical analyses revealed the excellent bone regeneration ability for composite hydrogel after implant into rat skull defect. Thus, our results indicated that composite scaffold can be applied as a new bone regeneration biomaterial to be applied as a local drug delivery system with good bone induction performance.

PLLA/POSS Nanofibers Loaded with Multitargeted pANG Composite Nanoparticles for Promotion of Vascularization in Shear Flow.

In vitro prevascularization is particularly important for the clinical application of tissue engineering scaffolds that require vascularization. The principal challenge is simulating the dynamic in vivo environment to promote the continuous growth of blood vessels. In this study, two targeting polypeptides are linked to the two ends of an amphiphilic block copolymer, polyethyleneimine-b-poly(lactide-co-3(S)-methyl-morpholine-2,5-dione)-b-polyethyleneimine (PEI-PLMD-PEI), and self-assembled to form positively charged nanoparticles (NPs), which can bind to negatively charged pANG through electrostatic interactions; the polypeptides are finally loaded into PLLA/polyhedral oligomeric silsesquioxane (POSS) porous fibers to prepare untargeted nanofibers (unTFs), targeted porous nanofibers (TFBs), and targeted nanofiber bundles. The effects of the porous nanofibers on human umbilical vein endothelial cell (HUVEC) transfection, spreading, proliferation, morphology, and expression of related factors are investigated under the action of shear flow force. The results show that the PLLA/POSS nanofibers can maintain stable release of multitargeted NPs for nearly 45 days. Both the dual-targeted porous NPs and shear flow improve the pANG transfection efficiency and promote cell proliferation, and they have a good synergistic effect. These results provide a potential strategy for designing HUVEC-specific gene carriers and using shear flow to enhance endothelialization.

Recurrence of an internal carotid artery aneurysm after complete exclusion by a Willis covered stent.

Treatment of selective intracranial aneurysms treated with a Willis covered stent is safe and effective. We describe a previously unreported case of a large, irregular, carotid-ophthalmic aneurysm that was treated with a Willis covered stent. An immediate angiogram after the procedure showed complete occlusion of the aneurysm. However, a six-month follow-up angiogram demonstrated contrast media filling of the aneurysm neck. To the best of our knowledge, this is the first report of a recurrent aneurysm treated with a Willis covered stent because of a membrane partially isolated with the stent. This case suggests that an aneurysm that is treated with a Willis covered stent might recanalise, and the risk of aneurysm rupture persists when the membrane of the stent is isolated with the stent. Therefore, follow-up angiography is necessary, even if an immediate angiogram shows complete aneurysm occlusion. Long-term follow-up is required, and the final outcome of such a case is still unknown.

Antibacterial poly (ethylene glycol) diacrylate/chitosan hydrogels enhance mechanical adhesiveness and promote skin regeneration.

Various functional active hydrogels have been widely applied in tissue regeneration, especially in fields of wound repair as they are similar to the natural extracellular matrix (ECM) and can maintain moist at the wound site. However, preparing a hydrogel with multifunctional properties including high mechanical properties, excellent biocompatibility and long-term antibacterial activity is still a challenge. Herein, we developed a series of double network hydrogels based on poly (ethylene glycol) diacrylate (PEGDA) and chitosan (CS) or thiolated chitosan (TCS). The hydrogels presented in situ forming properties, good mechanical strength, adhesiveness, antibacterial activity and biocompatibility. The sample with the optimal formula of 15 wt% of PEGDA and 2 wt% of CS or TCS showed excellent mechanical adhesiveness, sustained release of antibacterial peptide and plasmid DNA, and it significantly accelerated in vivo wound healing process in a full-thickness skin defect model by reducing the inflammation and promoting the angiogenesis, meaning that the prepared hydrogels are excellent candidates for wound dressing.

Functional polyhedral oligomeric silsesquioxane reinforced poly(lactic acid) nanocomposites for biomedical applications.

Polyhedral oligomeric silsesquioxane reinforced poly (L-lactic acid) nanocomposites (PLLA/POSS) were prepared to overcome the insufficient mechanical properties of PLLA. In order to improve the compatibility between the nanofillers and matrix, PLLA chains were grafted onto the POSS nanoparticles via microwave-assisted ring opening polymerization (ROP). Herein, a series of interface-modified polyhedral oligomeric silsesquioxane (POSS-(PLLA)32) nanoparticles with various PLLA tail lengths were synthesized and the influence of the structure and additional amount of POSS nanoparticles on the properties of PLLA based nanocomposites were studied. POSS nanoparticles exhibit effective nucleation activity and lead to a significant improvement in the mechanical strength, thermal stability and biocompatibility of the resulting nanocomposites. The addition of 6 wt% POSS-(PLLA)32 600 shows the optimal mechanical properties owing to has the longest PLLA tail length on POSS core, which possesses the optimal interfacial compatibility between POSS nanoparticles and PLLA. The Young's modulus improved by 57% and the tensile strength increased by 26.5% compared with neat PLLA. Moreover, the introduction of POSS nanoparticles lead to a porous fiber structure when processed by electrospinning and the nanofibrous scaffold effectively promoted cells adhesion and spreading. These results demonstrate the potential applications of the PLLA/POSS nanocomposites in tissue engineering and regenerative medicine.

Reduction-responsive shell cross-linked micelles derived from amphiphilic triblock copolymer as anticancer drug delivery carrier.

Stimuli-responsive crosslinked micelles are attractive carriers for in vivo delivery of water-insoluble therapeutic drugs due to their excellent stability during the blood circulation and high therapeutic effect resulting from the intelligent break-up of the crosslinked structure triggered by intracellular conditions as well as the subsequent fast drug release. Herein, novel amphiphilic triblock copolymer poly(l-lactide)-b-poly(allyl glycidyl ether/propanedithiol)-b-poly(ethylene glycol) (PLLA-b-P(AGE-SH)-b-PEG) was designed and synthesized by combining two successive ring-opening polymerizations and subsequent "thio-ene" reaction. Due to their unique amphiphilic architecture, copolymer PLLA-b-P(AGE-SH)-b-PEG could self-assemble into core-shell micelles, and the stimuli-responsive crosslinked micelles (SCMs) were obtained by crosslinking the P(AGE-SH) segments in the micellar shell under redox condition. The SCMs exhibited good stability against extensive dilution and slow sustained drug release in a simulated normal physiologycal environment, but fast release in the presence of GSH. As revealed by the cytotoxicity assay, the micelles from the copolymer PLLA-b-P(AGE-SH)-b-PEG showed excellent biocompatibility against HEK293T cells. Due to these combined good properties, the stimuli-responsive crosslinked micelles from PLLA-b-P(AGE-SH)-b-PEG are proposed to be an ideal carrier for the in vivo delivery of water-insoluble therapeutics.

Stereocomplexed micelle formation through enantiomeric PLA-based Y-shaped copolymer for targeted drug delivery.

In this study, a novel stereocomplexed micelle system was prepared from the self-assembly of enantiomeric PLA-based Y-shaped copolymers, i.e. folic acid-adamantane/ß-cyclodextrin-b-[poly(D-lactide)]2 (FA-AD/CD-b-(PDLA)2) and poly(2-dimethylaminoethyl methacrylate)-b-[poly(L-lactide)]2 (PDMAEMA-b-(PLLA)2) in aqueous solution. The newly designed Y-shaped copolymer FA-AD/CD-b-(PDLA)2 was prepared by a combination of "click" reaction and host guest interaction between FA-AD and CD-b-(PDLA)2. In addition, enantiomeric Y-shaped PDMAEMA-b-(PLLA)2 copolymer was synthesized through ring-opening polymerization (ROP) of L-lactide using three-head initiator with bromo and -OH at distal ends, followed by atom transfer radical polymerization (ATRP) of DMAEMA to obtain the desired macromolecular architecture. The resultant copolymers and their intermediates were characterized by 1H nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC) techniques. Due to the strong stereocomplexation interaction, FA-AD/CD-b-(PDLA)2 and PDMAEMA-b-(PLLA)2 mixture could self-assemble into stable mixed micelles in aqueous solution. Further, the stereocomplexed micelles exhibited excellent biocompatibility as revealed in the cytotoxicity assay. Together with the intrinsic biodegradability of PLA, it is envisioned that the stereocomplexed micelles developed in this study can be used as a promising nanocarrier for targeting drug delivery.

Time-of-flight secondary ion mass spectrometry analyses of vancomycin.

As an antibiotic that prevents and treats infections caused by Gram-positive bacteria such as Staphylococcus aureus, vancomycin incorporated in a biodegradable polymer poly(lactide-co-glycolide) provides opportunities to construct controlled-release drug delivery systems. Developments associated with this promising system have been largely concentrated on areas of drug delivery kinetics and biodegradability. In order to provide surface analytical approaches to this important system, the authors demonstrate applicability of time-of-flight secondary ion mass spectrometry (TOF-SIMS) in three-dimensional molecular imaging for a model system consisting of alternating layers of ploy(lactide-co-glycolide) and vancomycin. TOF-SIMS imaging clarified that the two chemicals can undergo phase separation when dimethyl sulfoxide is used as the solvent. The authors identified two diagnostic ions that are abundant and structural moieties of vancomycin. The results on TOF-SIMS imaging and depth profiling vancomycin provide useful information for further applications of TOF-SIMS in the development of antibiotic drug delivery systems involving the use of vancomycin.

Scaffold composed of porous vancomycin-loaded poly(lactide-co-glycolide) microspheres: A controlled-release drug delivery system with shape-memory effect.

Loading antibiotics in a biodegradable polymer matrix is an excellent way to control its release kinetics, which eliminates side effects caused by conventional administrations of the drug. This approach is especially beneficial for bone regeneration when using a scaffold made of a biodegradable polymer loaded with drug agents capable of controllable releases. In this case, the scaffold serves as a mechanical support to tissue formation and the drug agents may provide biomolecules to assist the tissue formation and/or provide antibiotics to prevent tissues from infections. Towards this goal, we have developed an approach to make vancomycin-loaded poly(lactide-co-glycolide) (PLGA) microspheres, from which we made scaffolds by compression molding. In this article we concentrate on characterizing the porosity and drug release profiles, as well as verifying shape-memory effect of the scaffolds. The scaffold was biodegradable and showed a much slower drug release profile than microspheres. We confirmed that our PLGA scaffolds recovered to their permanent shapes when heated to 45°C. We believe that these scaffolds will find applications in bone regeneration where both the use of antibiotics against infection and accommodation to spatial restrictions may be required.

Poly(L-lactide) crystallization topography directs MC3T3-E1 cells response.

Biomaterial surface topography significantly influences cellular form and function. Using poly(L-lactic acid) films with normal spherulites, banded spherulites, and amorphous surfaces as model substrates, we conducted a systematic assessment of the role for polymer crystallization induced surface morphologies on cell growth and contact guidance. Microscopy and image analysis showed that the MC3T3-E1 cells spread out in a random fashion on the amorphous substrate. At 24 h post-seeding, MC3T3-E1 cells on both types of spherulite surfaces were elongated and aligned along the spherulite radius direction. For the banded spherulite surface with radial stripes and coupling annular grooves, the cell orientation and cell nuclear localization were related to the grooves structure. With increasing time, this orientation preference was weaker. These results demonstrate that the patterning of polymer crystallization structure provide important signals for guiding cells to exhibit characteristic orientation and morphology especially in the early stages of regeneration.

Zirconium oxide ceramic foam: a promising supporting biomaterial for massive production of glial cell line-derived neurotrophic factor.

This study investigated the potential application of a zirconium oxide (ZrO2) ceramic foam culturing system to the production of glial cell line-derived neurotrophic factor (GDNF). Three sets of ZrO2 ceramic foams with different pore densities of 10, 20, and 30 pores per linear inch (PPI) were prepared to support a 3D culturing system. After primary astrocytes were cultured in these systems, production yields of GDNF were evaluated. The biomaterial biocompatibility, cell proliferation and activation of cellular signaling pathways in GDNF synthesis and secretion in the culturing systems were also assessed and compared with a conventional culturing system. In this study, we found that the ZrO2 ceramic foam culturing system was biocompatible, using which the GDNF yields were elevated and sustained by stimulated cell proliferation and activation of signaling pathways in astrocytes cultured in the system. In conclusion, the ZrO2 ceramic foam is promising for the development of a GDNF mass production device for Parkinson's disease treatment.