Peripheral Antimicrobial Peptide Gomesin Induces Membrane Protrusion, Folding, and Laceration.

Optical microscopy shows that the peripheral antimicrobial peptide (AMP) gomesin does not disrupt the bacterial membrane by forming stable transmembrane pores but induces lipid accumulation domains, which is followed by a sudden burst near the domains. The molecular action mechanisms of gomesin on vesicle and planar bilayer membranes are investigated in this work using coarse-grained molecular dynamics simulations. By comparing the membrane morphology and property changes induced by gomesin and the pore-forming AMP melittin, we determined that the amphiphilic shape of the AMPs is a key factor affecting the mechanism of cell death. The binding of wedge-shaped gomesin, with a small hydrophobic surface, onto the membrane induces protrusion and folding of the outer monolayer followed by sudden membrane lacerations at the axillae of the protuberances. Alternatively, cylinder-shaped melittins with comparable hydrophilic and hydrophobic surfaces destroy membranes by forming stable pores coexisting with exocytosis-like buddings and endocytosis-like invaginations. The multiple actions of AMPs on the bacterial membrane suggest diverse paradigms for designing molecular carriers for delivering drugs to the cell.

Peptide-Lipid Interaction Sites Affect Vesicles' Responses to Antimicrobial Peptides.

This article presents coarse-grained molecular dynamics simulations of pore-forming antimicrobial peptide melittin and its interactions with vesicles composed of a mixture of zwitterionic and anionic phospholipids. Besides creating holes in the membrane, the adsorption of melittin also induces vesicle budding, which can develop into vesiculation at high peptide concentrations, as well as vesicle invagination, which can eventually result in a corrugated membrane surface. These rich morphology changes are mediated by the curvature of the vesicles and the peptide concentration. Highly curved vesicles favor the recruitment of melittins with a higher density of binding sites. The peptides mainly penetrate into the membrane surface in monomers via hydrophobic interaction. Lowly curved vesicles recruit melittins with a low density of binding sites. Surplus peptides are prone to form oligomers and shallowly adsorb on the surface of membrane via electrostatic interaction. The penetration of monomers induces membrane pore formation and positive membrane curvature, which promote vesicle budding. The adsorption of oligomers induces negative membrane curvature, which promotes vesicle invagination. This work demonstrates that antimicrobial peptides adopt multiple actions to destroy bacterial membranes.

Facile one-pot synthesis of multifunctional polyphosphazene nanoparticles as multifunctional platform for tumor imaging.

By integrating imaging and drug-delivery in a single system, fluorescent nano-multifunctional imaging platforms can offer simultaneous diagnosis and therapy to diseases like cancer. However, the synthesis of such system involves a tedious, time-consuming, and multi-step process. Herein we report a facile method based on simple ultrasonication to synthesize highly cross-linked, monodispersed fluorescent polyphosphazene nanoparticles from hexachlorocyclotriphosphazene (HCCP) and dichlorofluorescein (FD). Various functional groups (folic acid, PEG-NH2, and methylene blue) can be "fastened" in situ onto the poly(cyclotriphosphazene-co-dichlorofluorescein) (PCTPDF) nanoparticles to expand its application as nano-multifunctional platform. All the nanoparticles were characterized spectrophotometrically, and morphology was established by the images obtained from scanning electron microscope (SEM). The synthesized multifunctional nanoparticles exhibited low toxicity and penetrated through the cytomembranes of human colon cancer (HCT 116) cells. When applied to in vivo tumor imaging using biologically engineered mouse model, methylene blue functionalized (PCTPDF@MB) nanoparticles exhibited excellent photodynamic activity and imaging ability. Thus, PCTPDF nanoplatform based on multi-functional fluorescent nanoparticles might offer an efficient solution to new age theranostics. Apart from diagnostics application, PCTPDF, as a nanoplatform, could also be utilized to achieve more comprehensive application in modern analytic chemistry. Graphical Abstract The table of contents.

Nuclear Factor I-C promotes proliferation and differentiation of apical papilla-derived human stem cells in vitro.

The transcription factor Nuclear Factor I-C (NFIC) has been implicated in the regulation of tooth root development, where it may be anticipated to impact on the behavior of stem cells from the apical papilla (SCAPs) and root odontoblast activity. We hypothesized that NFIC may provide an important target for promoting dentin/root regeneration. In the present study, the effects of NFIC on the proliferation and differentiation of SCAPs were investigated. Over-expression of NFIC increased cell proliferation, mineralization nodule formation and alkaline phosphatase (ALP) activity in SCAPs. Furthermore, NFIC up-regulated the mRNA levels of odontogenic-related markers, ALP, osteocalcin and collagen type I as well as dentin sialoprotein protein levels. In contrast, knockdown of NFIC by si-RNA inhibited the mineralization capacity of SCAPs and down-regulated the expression of odontogenic-related markers. In conclusion, the results indicated that upregulation of NFIC activity in SCAPs may promote osteo/odontoblastic differentiation of SCAPs.

Importance of CBCT setup verification for optical-guided frameless radiosurgery.

The purpose of this study is to quantify the discrepancy between optical guidance platform (OGP) frameless localization system (Varian) and Trilogy on-board imaging (OBI) system (Varian) for setting up phantom and stereotactic radiosurgery (SRS) patient; and to determine whether cone-beam CT (CBCT) is necessary for OGP patient setup, and compare CBCT and orthogonal kV-kV in term of their verification capability. Three different phantoms were used in the study: a custom-made phantom, a Penta-Guide phantom, and a RANDO phantom. Five patients using both OGP and CBCT setup and 14 patients using CBCT setup alone were analyzed. One patient who had big couch shifts discrepancy between OGP and CBCT was selected for further investigation. Same patient's CBCT and planning CT were fused. A RANDO phantom simulation experiment was performed using OGP setup with both CBCT and orthogonal kV-kV verification. For all of three phantom experiments, the shifts performed by CBCT beam and orthogonal kV-kV were all within 1 mm. Among five SRS patients using OGP setup, three had 3D couch corrections more than 3 mm. The image fusion of CBCT and planning CT clearly illustrated a tilt of bite-block in a patient's mouth. For 14 SRS patients using CBCT-guided setup, overall 3D correction was 3.3 ± 1.5 mm. RANDO phantom experiment demonstrated how a tilted bite-block caused isocenter shift. CBCT-calculated shifts are the same as expected, but kV-kV results differed by 1-2 mm if the initial head position is tilted. The bite-block tilting in patient's mouth is a major reason for the cause of positioning error for OGP frameless SRS setup. CBCT verification is necessary. CBCT provides more accurate couch corrections than orthogonal kV-kV when head was tilted. OGP is useful for detecting patient movement, but it does not necessarily imply that the isocenter has moved.

Peptide-Driven Proton Sponge Nano-Assembly for Imaging and Triggering Lysosome-Regulated Immunogenic Cancer Cell Death.

Triggering lysosome-regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning an "immune-cold" tumor "hot"-a key challenge faced by cancer immunotherapies. Proton sponge such as high-molecular-weight branched polyethylenimine (PEI) is excellent at rupturing lysosomes, but its therapeutic application is hindered by uncontrollable toxicity due to fixed charge density and poor understanding of resulted cell death mechanism. Here, a series of proton sponge nano-assemblies (PSNAs) with self-assembly controllable surface charge density and cell cytotoxicity are created. Such PSNAs are constructed via low-molecular-weight branched PEI covalently bound to self-assembling peptides carrying tetraphenylethene pyridinium (PyTPE, an aggregation-induced emission-based luminogen). Assembly of PEI assisted by the self-assembling peptide-PyTPE leads to enhanced surface positive charges and cell cytotoxicity of PSNA. The self-assembly tendency of PSNAs is further optimized by tuning hydrophilic and hydrophobic components within the peptide, thus resulting in the PSNA with the highest fluorescence, positive surface charge density, cell uptake, and cancer cell cytotoxicity. Systematic cell death mechanistic studies reveal that the lysosome rupturing-regulated pyroptosis and necroptosis are at least two causes of cell death. Tumor cells undergoing PSNA-triggered ICD activate immune cells, suggesting the great potential of PSNAs to trigger anticancer immunity.

Rational Designs of Biomaterials for Combating Oral Biofilm Infections.

Oral biofilms, which are also known as dental plaque, are the culprit of a wide range of oral diseases and systemic diseases, thus contributing to serious health risks. The manner of how to achieve good control of oral biofilms has been an increasing public concern. Novel antimicrobial biomaterials with highly controllable fabrication and functionalization have been proven to be promising candidates. However, previous reviews have generally emphasized the physicochemical properties, action mode, and application effectiveness of those biomaterials, whereas insufficient attention has been given to the design rationales tailored to different infection types and application scenarios. To offer guidance for better diversification and functionalization of anti-oral-biofilm biomaterials, this review details the up-to-date design rationales in three aspects: the core strategies in combating oral biofilm, as well as the biomaterials with advanced antibiofilm capacity and multiple functions based on the improvement or combination of the abovementioned antimicrobial strategies. Thereafter, insights on the existing challenges and future improvement of biomaterial-assisted oral biofilm treatments are proposed, hoping to provide a theoretical basis and reference for the subsequent design and application of antibiofilm biomaterials.

A miniaturized ultrasound transducer for monitoring full-mouth oral health: a preliminary study.

OBJECTIVE: To customize a miniaturized ultrasound transducer to access full-mouth B-mode, color Doppler, and spectral Doppler imaging for monitoring oral health. METHODS: A customized periodontal ultrasound transducer SS-19-128 (19 MHz, 128 channels) 1.8-cm wide and 1-cm thick was developed and connected to a data acquisition (DAQ) system. B-mode, color Doppler, and spectral Doppler data could all be collected with SS-19-128. The imaging resolution and penetration capacity of SS-19-128 were characterized on phantoms. The gingival thickness was measured on 11 swine teeth by SS-19-128 for comparison with conventional transgingival probing via Bland-Altman analysis and Pearson correlation. Five human subjects were then recruited to demonstrate B-mode and Doppler imaging by SS-19-128. RESULTS: The axial and lateral spatial resolution at 5.5 mm depth is 102.1 µm and 142.9 µm, respectively. The penetration depth in a tissue-mimicking phantom is over 30 mm. In vivo B-mode imaging of all 28 teeth was demonstrated on one human subject, and imaging of tooth #18 was accessed on five human subjects. Gingival thickness measurement compared with transgingival probing showed a bias of -0.015 mm and SD of 0.031 mm, and a r = 0.9235 (p < 0.0001) correlation. In vivo color and spectral Doppler imaging of the supraperiosteal artery in human gingiva was performed to generate hemodynamic information. CONCLUSIONS: The small size of SS-19-128 offers important advantages over existing ultrasound technology-more specifically, whole-mouth scanning/charting reminiscent of radiography. This is nearly a two-fold increase in the number of teeth that can be assessed versus conventional transducers.

Deep learning assisted sparse array ultrasound imaging.

This study aims to restore grating lobe artifacts and improve the image resolution of sparse array ultrasonography via a deep learning predictive model. A deep learning assisted sparse array was developed using only 64 or 16 channels out of the 128 channels in which the pitch is two or eight times the original array. The deep learning assisted sparse array imaging system was demonstrated on ex vivo porcine teeth. 64- and 16-channel sparse array images were used as the input and corresponding 128-channel dense array images were used as the ground truth. The structural similarity index measure, mean squared error, and peak signal-to-noise ratio of predicted images improved significantly (p < 0.0001). The resolution of predicted images presented close values to ground truth images (0.18 mm and 0.15 mm versus 0.15 mm). The gingival thickness measurement showed a high level of agreement between the predicted sparse array images and the ground truth images, as indicated with a bias of -0.01 mm and 0.02 mm for the 64- and 16-channel predicted images, respectively, and a Pearson's r = 0.99 (p < 0.0001) for both. The gingival thickness bias measured by deep learning assisted sparse array imaging and clinical probing needle was found to be <0.05 mm. Additionally, the deep learning model showed capability of generalization. To conclude, the deep learning assisted sparse array can reconstruct high-resolution ultrasound image using only 16 channels of 128 channels. The deep learning model performed generalization capability for the 64-channel array, while the 16-channel array generalization would require further optimization.

Emerging Liquid Metal Biomaterials: From Design to Application.

Liquid metals (LMs) as emerging biomaterials possess unique advantages including their favorable biosafety, high fluidity, and excellent electrical and thermal conductivities, thus providing a unique platform for a wide range of biomedical applications ranging from drug delivery, tumor therapy, and bioimaging to biosensors. The structural design and functionalization of LMs endow them with enhanced functions such as enhanced targeting ability and stimuli responsiveness, enabling them to achieve better and even multifunctional synergistic therapeutic effects. Herein, the advantages of LMs in biomedicine are presented. The design of LM-based biomaterials with different scales ranging from micro-/nanoscale to macroscale and various components is explored in-depth to promote the understanding of structure-property relationships, guiding their performance optimization and applications. Furthermore, the related advanced progress in the development of LM-based biomaterials in biomedicine is summarized. Current challenges and prospects of LMs in the biomedical field are also discussed.

A Nucleus-Targeted Nanosystem Integrated with Photodynamic Therapy and Chemotherapy.

Minimally invasive photodynamic therapy, destroying lesions with a light-activated photosensitizer, has been increasingly performed since it is highly efficiency, safe, synergistically compatible, repeatable, and minimally-invasive, with few adverse reactions. However, the most present photosensitizer or nanodrug delivery system containing a photosensitizer can target tumor cells but rarely cell nuclei. In this regard, the nucleus-targeting drug delivery system has been developed aiming impair tumor cells in an efficient and direct manner. In this study, the cationic liposome (Clip) drug delivery system integrated with low dose nucleus-targeting chemotherapeutic drug Doxorubicin (DOX) and photosensitizer AlPcS4 (Clip-AlPcS4@DOX) was synthesized. Among them, Clip was used to efficiently load drugs into cells almost at the same time, low dose DOX was used to open the channel for the materials to enter the nucleus on the premise of ensuring low cytotoxicity and then introduced photosensitizer into the nucleus, AlPcS4 photosensitizer was used to damage directly and efficiently through the photodynamic therapy (PDT) effect after entering the nucleus. In summary, a nucleus-targeting nanodrug delivery system (Clip-AlPcS4@DOX) was designed and synthesized and could be induced cell apoptosis more quickly and efficiently. Therefore, it could be a promising nucleus-targeting nanosized reagent integrating the PDT and chemotherapy for gastric therapy.

Posterior photoacoustic/ultrasound imaging of the periodontal pocket with a compact intraoral transducer.

Periodontitis is a public issue and imaging periodontal pocket is important to evaluate periodontitis. Regular linear transducers have limitations in imaging the posterior teeth due to their geometry restrictions. Here we characterized a transducer that can image the posterior teeth including assessment of periodontal pockets via a combination of photoacoustic and ultrasound imaging. Unlike conventional transducer design, this device has a toothbrush-shaped form factor with a side-view transducer to image molars (total size: 1 ×1.9 cm). A laser diode was integrated as the light source to reduce the cost and size and facilitates clinical transition. The in vivo imaging of a molar of a periodontal patient demonstrated that the transducer could image in the posterior area of gum in vivo; the value determined by imaging was within 7 % of the value measured clinically.

Near-infrared light-triggered polypyrrole promotes C2C12 cell differentiation and inhibits TNF-α induced myotube atrophy.

Treatment of skeletal muscle atrophy and strengthening the muscles remain a challenge in modern medicine. Studies have shown that photobiomodulation can inhibit skeletal muscle atrophy and aid in functional recovery. Near-infrared radiation (NIR) therapy has emerged as a complementary therapy for the treatment of skeletal muscle atrophy, but its underlying mechanism remains unclear. Polypyrrole (PPy) is an organic polymer with strong near-infrared absorption, which can generate heat from absorbed NIR. In this study, MHC immunofluorescence staining was performed on C2C12 myoblasts to investigate the differentiation of C2C12 cells after NIR-triggered PPy exposure. As TNF-α-induced C2C12 myotubes were used as a model of muscular atrophy. Giemsa staining was used to determine the myotube diameter. Western blot analysis was performed to examine the proteins involved in the differentiation and atrophy of muscle cells, as well as in the Akt/P70S6K signaling pathway. PPy triggered by NIR promoted the differentiation of C2C12 cells, inhibited C2C12 myotube atrophy caused by TNF-α, and downregulated the expression levels of Atrogin-1 and MuRF 1 protein. In addition, we determined that Akt/P70S6K signaling pathway activity plays a crucial role in the therapeutic effect of NIR-triggered polypyrrole, which was further confirmed by the administration of the Akt inhibitor GDC0068. The optimal conditions for these effects were a PPy concentration of 0.125 mg/ml and NIR exposure for 80 s. We show that the photothermal effect of PPy triggered by near-infrared light can increase the beneficial effects of NIR, promote the differentiation of C2C12 cells, and improve C2C12 myotube atrophy, laying a foundation for its future clinical use.

MMP-2 Inhibitor-Mediated Tumor Microenvironment Regulation Using a Sequentially Released Bio-Nanosystem for Enhanced Cancer Photo-Immunotherapy.

Combining photodynamic therapy (PDT) with natural killer (NK) cell-based immunotherapy has shown great potential against cancers, but the shedding of NK group 2, member D ligands (NKG2DLs) on tumor cells inhibited NK cell activation in the tumor microenvironment. Herein, we assembled microenvironment-/light-responsive bio-nanosystems (MLRNs) consisting of SB-3CT-containing ß-cyclodextrins (ß-CDs) and photosensitizer-loaded liposomes, in which SB-3CT was considered to remodel the tumor microenvironment. ß-CDs and liposomes were linked by metalloproteinase 2 (MMP-2) responsive peptides, enabling sequential release of SB-3CT and chlorin e6 triggered by the MMP-2-abundant tumor microenvironment and 660 nm laser irradiation, respectively. Released SB-3CT blocked tumor immune escape by antagonizing MMP-2 and promoting the NKG2D/NKG2DL pathway, while liposomes were taken up by tumor cells for PDT. MLRN-mediated photo-immunotherapy significantly induced melanoma cell cytotoxicity (83.31%), inhibited tumor growth (relative tumor proliferation rate: 1.13% of that of normal saline) in the xenografted tumor model, and enhanced tumor-infiltrating NK cell (148 times) and NKG2DL expression (9.55 and 16.52 times for MICA and ULBP-1, respectively), achieving a synergistic effect. This study not only provided a simple insight into the development of new nanomedicine for programed release of antitumor drugs and better integration of PDT and immunotherapy but also a novel modality for clinical NK cell-mediated immunotherapy against melanoma.

Photoacoustic imaging of posterior periodontal pocket using a commercial hockey-stick transducer.

SIGNIFICANCE: Photoacoustic imaging has shown advantages over the periodontal probing method in measuring the periodontal probing depth, but the large size of conventional photoacoustic transducers prevents imaging of the more posterior teeth. AIM: Our aim is to develop a photoacoustic imaging system to image the more posterior periodontal pocket. APPROACH: We report a clinical "hockey-stick"-style transducer integrated with fibers for periodontal photoacoustic imaging. Cuttlefish ink labeled the periodontal pocket as the photoacoustic contrast agent. RESULTS: We characterized the imaging system and then measured the pocket depth of 35 swine teeth. Three raters evaluated the performance of the hockey-stick transducer. The measurements between the Williams probing (gold standard) and the photoacoustic methods were blinded but highly correlated. We showed a bias of ∼0.3 mm for the imaging-based technique versus Williams probing. The minimum inter-reliability was over 0.60 for three different raters of varying experience, suggesting that this approach to measure the periodontal pocket is reproducible. Finally, we imaged three pre-molars of a human subject. We could access more upper and posterior teeth than conventional linear transducers. CONCLUSIONS: The unique angle shape of the hockey-stick transducer allows it to image more posterior teeth than regular linear transducers. This study demonstrated the ability of a hockey-stick transducer to measure the periodontal pocket via photoacoustic imaging.

Experts' consensus on space management of mixed dentition.

The mixed dentition stage is the period between primary and permanent dentition. The following biological processes are complicated and variable: jaw growth, development of inherited permanent teeth embryo, physiological absorption of primary teeth, restoration of surrounding alveolar bones, and growth and function establishment of soft tissues. For the normal development of the jaw, the establishment of the good occlusion relationship, development, and function of soft tissue is very important, whether or not the primary teeth are normally replaced by the permanent teeth in the mixed dentition stage. The eruption space is linked to the normal replacement of primary and permanent teeth. The presence of a mixed dentition space results in the incidence and progression of malocclusion and impacts the normal growth and development of the occlusion, jaw, and face. Space management in the mixed dentition stage is a crucial means to prevent and reduce malocclusion. The following were discussed and analyzed: the possible space problems, why the size of the space was affected, the content that needs to be assessed, and the methods of space management in the mixed dentition that can be used to unify and standardize the management of mixed dentition. This paper was developed to serve as a guide for regulated space management during the mixed dentition period.

Synthesis and photovoltaic properties of ester group functionalized polythiophene derivatives.

To increase the open circuit voltage (V(OC)) of polymer solar cells (PSCs) based on polythiophene, two new ester group functionalized polythiophene derivatives, PCTDT and PCTBDT, were designed and synthesized via alternating copolymerization of thiophene-3-carboxylate (CT) with the 2,2'-bithiophene (DT) and benzodithiophene (BDT) units, respectively. The resulting copolymers exhibited broad and strong absorptions in the visible region, which was similar to that of the commonly used poly(3-hexylthiophene) (P3HT). Through cyclic voltammetry measurements, it was found that both copolymers showed lower HOMO energy levels (-5.27 eV for PCTDT and -5.36 eV for PCTBDT) than that of P3HT (-5.03 eV), indicating that the HOMO energy level could be efficiently reduced by introducing the ester group into the polymer side chain. Photovoltaic properties of the copolymers blended with [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) as electron acceptor were investigated. The obtained two devices possessed both relatively large short circuit current (I(SC)) and higher V(OC) than that of P3HT:PCBM blend. For PCTBDT:PCBM blend, a power conversion efficiency (PCE) up to 2.32%, an I(SC) of 6.94 mA · cm(-2), and a V(OC) of 0.80 V were observed while PCTDT:PCBM system demonstrated a PCE of 1.75% with a V(OC) of 0.68 V.

Motion-compensated noninvasive periodontal health monitoring using handheld and motor-based photoacoustic-ultrasound imaging systems.

Simultaneous visualization of the teeth and periodontium is of significant clinical interest for image-based monitoring of periodontal health. We recently reported the application of a dual-modality photoacoustic-ultrasound (PA-US) imaging system for resolving periodontal anatomy and periodontal pocket depths in humans. This work utilized a linear array transducer attached to a stepper motor to generate 3D images via maximum intensity projection. This prior work also used a medical head immobilizer to reduce artifacts during volume rendering caused by motion from the subject (e.g., breathing, minor head movements). However, this solution does not completely eliminate motion artifacts while also complicating the imaging procedure and causing patient discomfort. To address this issue, we report the implementation of an image registration technique to correctly align B-mode PA-US images and generate artifact-free 2D cross-sections. Application of the deshaking technique to PA phantoms revealed 80% similarity to the ground truth when shaking was intentionally applied during stepper motor scans. Images from handheld sweeps could also be deshaken using an LED PA-US scanner. In ex vivo porcine mandibles, pigmentation of the enamel was well-estimated within 0.1 mm error. The pocket depth measured in a healthy human subject was also in good agreement with our prior study. This report demonstrates that a modality-independent registration technique can be applied to clinically relevant PA-US scans of the periodontium to reduce operator burden of skill and subject discomfort while showing potential for handheld clinical periodontal imaging.

Reversible photoswitchable fluorescence in thin films of inorganic nanoparticle and polyoxometalate assemblies.

A novel type of inorganic hybridized ultrathin film consisting of Preyssler-type polyoxometalates K(14)[Na(H(2)O)P(5)W(30)O(110)] (Na-POMs) and CdSe@CdS nanoparticles (NPs) was prepared on the solid substrates by a layer-by-layer assembly technique. The film exhibits reversible fluorescence switching behavior under control of irradiation with either UV light or visible light, which is ascribed to the selective occurrence of fluorescence resonance energy transfer between luminescent NPs and different states of photochromic Na-POMs.

Synthetic/natural blended polymer fibrous meshes composed of polylactide, gelatin and glycosaminoglycan for cartilage repair.

Electrospinning is a common and effective technology used for the fabrication of biomimetic nanofibers targeting tissue regeneration applications. As for cartilage regeneration, nanofibers containing natural components derived from cartilage extracellular matrix (ECM) are preferred. However, it is not easy an task to electrospin glycosaminoglycan (GAG) like hyaluronic acid (HA) and chondroitin sulfate (CS) by themselves. In this study, HA and/or CS were co-electrospun with poly(L-lactide) (PLLA) or PLLA/gelatin (1:1 in weight ratio) to obtain GAG-containing composite nanofibers. All the prepared composite nanofibers were non-cytotoxic, able to support cell attachment, spread and proliferation. In the differentiation studies, the PLLA/GAG and the PLLA/gelatin/GAG nanofibers demonstrated stronger capacities in promoting the chondrogenic differentiation of both the bone marrow mesenchymal stromal cells (BMSCs) and chondrocytes than the respective PLLA and PLLA/gelatin nanofibers, even in the proliferation medium without extra inductive factors. The incorporation of gelatin greatly improved the hydrophilicity of the fibrous meshes. At the meantime, the PLLA/gelatin/GAG nanofibers were more efficient than the PLLA/GAG nanofibers in enhancing the chondrogenic differentiation. It was found that the PLLA/gelatin/HA/CS (HA and CS in 1:1 weight ratio) nanofibers demonstrated a stronger synergetic effect on up-regulating chondrogenesis than both the PLLA/gelatin/HA and the PLLA/gelatin/CS nanofibers, when the GAG amounts in all the preparations were controlled as 3 wt.%. Herein, GAG-containing composite nanofibers were successfully electrospun and their potentials for cartilage repair were proved.