Modulating of Bouligand Structure and Chirality Constructed Bionically Based on the Self-Assembly of Chitin Whiskers.

Chitin can self-assemble into a liquid crystal phase with supramolecular chirality and Bouligand structure, which is widely found in the exoskeletons of arthropods. However, bionically replicating this structure via the self-assembly of chitin whiskers (CHWs) is still a challenge. Here, the effects of several internal and external parameters on the self-assembly of CHWs were revealed based on liquid crystal phase, chirality, Bouligand structure, and rheological properties. The formation of chiral liquid crystal phase and Bouligand structure largely depends on the concentration of CHWs and, meanwhile, is affected by the aspect ratio and zeta potential of CHWs and the self-assembly time. Impressively, introducing electrolytes and changing pH significantly affect the thickness of the electrical double layer, thereby also affecting the self-assembly of CHWs. This study offers a comprehensive understanding of CHWs' self-assembly process, which is beneficial for the bionic design of new nature-inspired functional materials with chiral characteristic and Bouligand structure.

N-acyl homoserine lactone mediating initial adhesion of microalgal biofilm formation.

While pioneering methods have demonstrated that bacterial N-acyl homoserine lactone (AHL) signaling molecules can influence the growth and self-aggregation of suspended microalgae, whether AHLs can affect the initial adhesion to a carrier has remained an open question. Here we revealed that the microalgae exhibited different adhesion potential under AHL mediation, where the performance was affiliated to both AHL types and concentrations. The result can be well explained by the interaction energy theory, where the energy barrier between the carriers and the cells varied due to AHL mediation. Depth analyses revealed that AHL acted through modifying the properties of the surface electron donor of the cells, which were dependent upon three major components, i.e., extracellular protein (PN) secretion, the PN secondary structure, and the PN amino acid composition. These findings expand the known diversity of AHLs mediation on microalgal initial adhesion and metabolisms, which may interface with other major cycles and become helpful to theoretically guide the application of AHLs in microalgal culture and harvesting.

Novel Digital Light Processing Printing Strategy Using a Collagen-Based Bioink with Prospective Cross-Linker Procyanidins.

Three-dimensional (3D) bioink plays a vital role in the construction of tissues and organs by 3D bioprinting. Collagen has outstanding biocompatibility and is widely used in the field of tissue engineering. However, due to poor mechanical properties and slow self-assembly, it is challenging to manufacture high-precision 3D bioprinted collagen scaffolds. Herein, a novel digital light processing (DLP) bioink which can satisfy the printing of complex structures has been developed. This photocurable bioink is based on collagen and supplemented with a small amount of procyanidins (PA) as a cross-linking agent. The low concentration of collagen gives the bioink good fluidity and excellent biocompatibility, and a small amount of PA increases the cross-linking density of the system to obtain better mechanical properties. Using commercial digital light processing (DLP) printers, this collagen-based ink can effectively print structures with micrometer resolution, and the fidelity of the 3D structures can reach above 90%. Cells were able to be loaded in the bioink and distributed uniformly in the collagen scaffold in an unscathed way. This photocurable collagen bioink has broad application potential in DLP 3D bioprinting.

Impacts of chitosan oligosaccharide (COS) on angiogenic activities.

It has been proved that chitosan oligosaccharide (COS) has a more favorable therapeutic applications such as wound healing and anti-tumor treatment, and can affect angiogenesis. For better understanding the effect of COS on angiogenic activities at cellular level, COS with different concentration and degree of polymerization (DP) were used to culture human umbilical vein endothelial cells (HUVECs) in this work. Cell proliferation activity, cell morphology, cell migration and angiogenesis associated factor expression of HUVECs were evaluated. The results indicated that COS at a high concentration of 400 µg/mL (COS(400)) and DP of 6 (Chitinhexaose Hydrochloride, COS6) had inhibitory effect on angiogenic activities of HUVECs. Specifically, COS(400) and COS6 inhibited cell proliferation activity, cell migration, and vascular endothelial cell growth factor (VEGF) expression of HUVECs. While COS at a low concentration (<400 µg/mL) and suitable polymerization degrees (DP < 6) had little significant effect on cell proliferation, migration, and VEGF expression of HUVECs, showing dose-dependent effect. These findings provided insight for the potential use of COS, for broadening its future applications in biomedical fields and functional materials area. It also helped guide the design and synthesis of chitosan-based materials as an angiogenesis inhibitor for anti-angiogenic therapy.

Clay Nanotubes Aligned with Shear Forces for Mesenchymal Stem Cell Patterning.

Aligned halloysite nanotubes on solid substrates are fabricated by a shearing method with brush assistance. These clay nanotubes are aligned by shear force in strip-like patterns accomplished with drying ordering at elevated temperatures. The nanotubes' orientation is governed by "coffee-ring" formation mechanisms depending on the dispersion concentration, nanotube charge, and speed of thermos-evaporation. Polarized light irradiated through the patterns demonstrates birefringence and confirms the orientation. Scanning electron microscopy and atomic force microscopy show that the nanotubes are aligned along the direction of the wetting lines above 4 wt%, while they are not oriented at lower concentrations. Halloysite concentration, drying temperature, and type of brush fibers affect the pattern ordering. The aligned halloysite systems on glass, tissue culture plates, and polymer films, provide a promising platform for biocell guiding. Human foreskin fibroblasts proliferated well on the aligned clay patterns and the cell orientation agrees with the nanotube direction. Human bone mesenchymal stem cells (HBMSCs) are also cultured on the organized halloysite coating. The clay patterns support HBMSC proliferation with alignment, and such nanostructured substrates promote osteogenesis differentiation without growth factors. This facile method for preparing aligned halloysite patterns on solid substrates is very promising for surface modification in biotissue engineering.

Fabrication of chitin/graphene oxide composite sponges with higher bilirubin adsorption capacity.

Chitin/graphene oxide (Ch/GO) composite sponges had been synthesized in 11 wt% NaOH/4 wt% urea aqueous solution by a simple method. The structure, thermal stability and mechanical properties of the composite sponges were investigated by scanning electron microscopy, Fourier-transform infrared spectroscopy, wide-angle X-ray diffraction, thermogravimetric analysis, and compressive strength measurements. The results revealed that chitin and GO were mixed homogeneously. Interestingly, the composite sponges showed meso-macroporous structure, which played an important role in improving their adsorption properties. Besides, thermal stability and mechanical properties were significantly improved compared with pure chitin sponges. Taking advantages of these fantastic characteristics, the maximum adsorption capacity of composite sponges for bilirubin was up to 422.9 mg/g under the optimized condition, which was not only significantly higher than the adsorption capacities of pure chitin sponges, but also superior to those of many reported adsorbents for removal of bilirubin. Furthermore, blood compatibility evaluations confirmed that this blended sponges had negligible hemolysis and coagulation. Therefore, this work provided a potential possibility to offer Ch/GO composite sponges for removal of bilirubin.

Study on the interaction mechanism between cefradine and Chlamydomonas reinhardtii in water solutions under dark condition.

Our research investigated the hormesis effect of cefradine on the specific growth rates (µ) of single-celled algae (Chlamydomonas reinhardtii) from aqueous solutions. We found the specific growth rate of C. reinhardtii slightly increased with cefradine concentrations within the range 0.5-10 mg/L. Effects of algae density, initial solution pH, and temperature on the adsorption batch assays were investigated. The optimum conditions for cefradine adsorption occurred at a density of 5 × 106 algae cells/mL, a solution pH of 7.0, and a temperature of 25.0 °C. A Box-Behnken design was employed to evaluate correlations between influential factors and cefradine adsorption. The results showed a significant interaction between algae density and temperature. The maximum removal rate could reach 50.13% under the optimal conditions. Additionally, the adsorption mechanisms were explored through Langmuir and Freundlich isotherm equations, adsorption kinetics, and thermodynamics. The results suggested that the adsorption process was monolayer, spontaneous, and endothermic with an increase in randomness at the algae-solution interface, which followed a pseudo-second-order model. All the data indicated that the alga performed a better removal capacity in the antibiotic-containing wastewater treatment process. This study lays the groundwork for a better understanding of the interaction mechanism between cefradine and Chlamydomonas reinhardtii in water solutions under dark condition.

Self-Assembling Halloysite Nanotubes into Concentric Ring Patterns in a Sphere-on-Flat Geometry.

Highly ordered and concentric ring patterns consisting of halloysite nanotubes (HNTs) with hierarchical cholesteric architectures are prepared by evaporation-induced self-assembly in a sphere-on-flat geometry. The structure and properties of HNTs are investigated. HNTs show a perfect tubular morphology on the nanoscale with high dispersion stability in water. Upon drying the HNTs aqueous suspension in a sphere-on-flat confined space, regular concentric HNTs rings are formed on the substrate via a self-assembly process. The widths of the inner and outer rings and the spacing between the adjacent rings increase with an increase in the concentration of the HNTs suspension. The highly ordered and concentric HNTs rings show a pronounced Maltese cross-like pattern under crossed polarizers, which suggests the formation of hierarchical cholesteric architectures. Scanning electron microscopy and atomic force microscopy observations show a disclination alignment of HNTs in the ring strips, especially with a high concentration of the HNTs suspension. The patterned rough surfaces of the HNTs show low cytotoxicity and can be used as a cell-supporting scaffold. The HNTs rings can guide the growth and orientation of C2C12 myoblast cells perpendicular to the rings. This work provides a simple, repeatable, mild, and high-efficiency method for obtaining HNTs with hierarchical architectures, which show potential for a large variety of applications, for example, in vascular grafts and skin regeneration.

Fabrication of Hydroxyapatite Nanofiber via Electrospinning as a Carrier for Protein.

Hydroxyapatite (HAp) nanoscale fibers were produced by combining electrospinning and a sol­gel system. The fibers were electrospun from a mixture of polymer-calcium phosphate (CaP) sol, then subjected to heat treatment. XRD, FTIR, SEM and TEM with HRTEM analyses confirmed HAp nanofibers with the average fiber diameters varied from 80 to 110 nm can be produced. The effects of concentrations of CaP sol and thermal treatment on the structure of nanofiber were studied. Decreasing the concentration of sol in the mixture can produce HAp fibers with smaller diameters; while higher concentrations of the sol resulted in HAp ceramic fibers with porous structures. The possibility of using HAp nanofiber particles as a controlled release carrier of protein was examined. The amount of protein adsorbed onto HAp fibers decreased as the concentration of the sol and the temperature of heat treatment increased. The sustained release of Bovine serum albumin (BSA) from HAp nanofiber was observed. The study provides information relevant to the fabrication and bioapplication of ceramic nanofiber.

Monoclinic Hydroxyapatite Nanoplates Hybrid Composite with Improved Compressive Strength, and Porosity for Bone Defect Repair: Biomimetic Synthesis and Characterization.

Calcium phosphate cement (CPC) has been used for bone restoration despite its intrinsic fragile property. In order to enhance the CPC mechanical properties, biopolymers were introduced as filler to prepare CPC based cements. Chitosan/tetracalcium phosphate (TTCP)/dicalcium phosphate anhydrous (DCPA) based cement for bone repair has been prepared in the study. Solidification of the prepared cement was carried out in a simulate body fluid at 37 degrees C. The introduction of chitosan improved the mechanical performance of the as-prepared CPC hybrid nanocomposite. FTIR, SEM, TEM, HRTEM, XRD, and SAED were used to characterize the CPC nanocomposite. Data simulations have been performed to assist in determining the crystalline phase/s in the CPC hybrid nanocomposite. Based on the SAED, HRTEM measurements and data simulations, a monoclinic phase of hydroxyapatite (HAP) with a plate-like structure was obtained in the CPC system, which is believed to be responsible for the observed enhancement in CPC mechanical properties. The obtained composite has a biocompatibility comparable to that of commercial sample.

[Effect of Chit-oligosaccharide/Collagen Composite Gels on Pre-osteoblastic MC3T3-E1s Differentiation].

Chit-oligosaccharide(COS)is a low-molecular,water-soluble mass with higher biological activity,which can be absorbed by human body easily and interact with cells directly.Based on the excellent biological properties of collagen(Col)and COS,a series of Col and COS composite hydrogel(Col/COSn)was constructed in this study.The effect of composite hydrogel on cells proliferation,differentiation and related osteogenic gene expression was evaluated on pre-osteoblast MC3T3-E1 s.The experimental results showed that all the Col/COS composite gels could promote the growth of MC3T3-E1 s,proliferation and bone related gene expression compared to that of pure Col gels.And there was significant difference among the composite hydrogel groups with different degrees of polymerization of COS.The effect of the composite gel which contained chitotetraose(COS4)or chitohexaose(COS6)on the cells proliferation was better than that of other groups,while on cells differentiation and related osteogenic gene expression the composite gel contained chitopentaose(COS5)was the best in all the groups.

Investigation of the antimicrobial activity and biocompatibility of magnesium alloy coated with HA and antimicrobial peptide.

Implant-associated infection is one of the biggest problems in orthopedic surgery. Antimicrobial peptides (AMPs) are well-known components of the innate immunity and less susceptible to the development of pathogen resistance compared to conventional antibiotics. Magnesium alloys as potential biodegradable bone implants have been received much attention in biomaterials field. This study investigated the deposition of calcium phosphate (CaP) coatings and loading of AMPs on the magnesium alloy surface by a biomimetic method. Scanning electron microscope (SEM) results presented that a microporous and plate-like CaP coating was processed on the magnesium alloy surface. X-ray diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis showed the main component of coating was hydroxyapatite (HA). Degradation assay in vitro showed that the HA coating deposited onto the magnesium alloy was corroded more slowly than the bare one. The amount of AMP loaded in the HA coating was 11.16±1.99 µg/cm2. The AMP loaded onto HA coatings had slow release for 7 days. The AMP-loaded coating showed antimicrobial activity against Staphylococcus aureus. Its bacterial inhibition rate exceeded 50% after 4 days and the antibacterial effect was sustained for 7 days. The coated magnesium alloys loaded with AMP could improve rat bone marrow mesenchymal stem cells (rBMMSCs) proliferation. Furthermore, it could also promote alkaline phosphatase (ALP) activity of rBMMSCs. Both radiographic evaluation and histopathology analysis demonstrated that implantation of the coated magnesium alloy into the rabbit femoral condyle had promoted bone repair and showed anti-inflammatory effect. The results showed that the AMP loaded onto HA coatings on the magnesium alloy surface could be considered an ideal orthopedic implant against S. aureus infection.

Improved stability and cell response by intrinsic cross-linking of multilayers from collagen I and oxidized glycosaminoglycans.

Stability of surface coatings against environmental stress, such as pH, high ionic strength, mechanical forces, and so forth, is crucial for biomedical application of implants. Here, a novel extracellular-matrix-like polyelectrolyte multilayer (PEM) system composed of collagen I (Col I) and oxidized glycosaminoglycans (oGAGs) was stabilized by intrinsic cross-linking due to formation of imine bonds between aldehydes of oxidized chondroitin sulfate (oCS) or hyaluronan (oHA) and amino groups of Col I. It was also found that Col I contributed significantly more to overall mass in CS-Col I than in HA-Col I multilayer systems and fibrillized particularly in the presence of native and oxidized CS. Adhesion and proliferation studies with murine C3H10T1/2 embryonic fibroblasts demonstrated that covalent cross-linking of oGAG with Col I had no adverse effects on cell behavior. By contrast, it was found that cell size and polarization was more pronounced on oGAG-based multilayer systems, which corresponded also to the higher stiffness of cross-linked multilayers as observed by studies with quartz crystal microbalance (QCM). Overall, PEMs prepared from oGAG and Col I give rise to stable PEM constructs due to intrinsic cross-linking that may be useful for making bioactive coatings of implants and tissue engineering scaffolds.

In Situ Construction of Morphologically Different Hydroxyapatite-Mineralized Structures on a Three-Dimensional Bionic Chitin Scaffold.

Slow healing at the tendon-bone interface is a prominent factor in the failure of tendon repair surgeries. The development of functional biomaterials with 3D gradient structures is urgently needed to improve tendon-bone integration. The crystalline form of hydroxyapatite (HAP) has a crucial impact on cell behavior, which directly influences protein adsorption, such as bone morphogenetic protein 2, the adhesion, proliferation, and osteogenic differentiation with cells. This work aimed to generate gradient mineral structures in situ by stabilizing calcium and phosphate ions using a polymer-induced liquid precursor process. To regulate the crystalline growth of HAP at the interface of ß-chitin, this work made use of the surface properties of the organic matrix found in cuttlefish bone. These techniques allowed us to prepare an organic-inorganic composite gradient scaffold comprising plate-like HAP mineralized in situ on the surface of the scaffold and fibrous HAP in the scaffold's interior. Organic-inorganic composite gradient materials are anticipated for use in tendon-bone healing produced via the in situ construction of gradient-distributed HAP mineralization layers having varying crystalline morphologies on chitin scaffolds that possess a three-dimensional bionic structure.

Creating a bionic scaffold via light-curing liquid crystal ink to reveal the role of osteoid-like microenvironment in osteogenesis.

Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics, including viscoelasticity and liquid crystal (LC) state. Thus, integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair. Despite extensive research on viscoelasticity, the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials. Moreover, the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood. Here, we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink. By utilizing these LC scaffolds as 3D research models, we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation, while viscoelasticity operates via mechanotransduction pathways. Additionally, our investigation revealed a synergistic effect between LC state and viscoelasticity, amplifying cell-protein interactions and osteogenic mechanotransduction processes. Furthermore, the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing. Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis, offering valuable insights for the biomimetic design of bone repair scaffolds.

A Wood-Derived Periosteum for Spatiotemporal Drug Release: Boosting Bone Repair through Anisotropic Structure and Multiple Functions.

Existing artificial periostea face many challenges, including difficult-to-replicate anisotropy in mechanics and structure, poor tissue adhesion, and neglected synergistic angiogenesis and osteogenesis. Here, inspired by natural wood (NW), a wood-derived elastic artificial periosteum is developed to mimic the structure and functions of natural periosteum, which combines an elastic wood (EW) skeleton, a polydopamine (PDA) binder layer, and layer-by-layer (LBL) biofunctional layers. Specifically, EW derived from NW is utilized as the anisotropic skeleton of artificial periosteum to guide cell directional behaviors, moreover, it also shows a similar elastic modulus and flexibility to natural periosteum. To further enhance its synergistic angiogenesis and osteogenesis, surface LBL biofunctional layers are designed to serve as spatiotemporal release platforms to achieve sequential and long-term release of pamidronate disodium (PDS) and deferoxamine (DFO), which are pre-encapsulated in chitosan (CS) and hyaluronic acid (HA) solutions, respectively. Furthermore, the combined effect of PDA coating and LBL biofunctional layers enables the periosteum to tightly adhere to damaged bone tissue. More importantly, this novel artificial periosteum can boost angiogenesis and bone formation in vitro and in vivo. This study opens up a new path for biomimetic design of artificial periosteum, and provides a feasible clinical strategy for bone repair.

Exosome-loaded hyaluronic acid hydrogel composite with oxygen-producing 3D printed polylactic acid scaffolds for bone tissue repair and regeneration.

Bone defects can interfere with bone healing by disrupting the local environment, resulting in vascular damage and hypoxia. Under these conditions, insufficient oxygen availability is a significant factor that exacerbates disease by blocking angiogenesis or osteogenesis. Exosomes play a crucial role in intercellular communication and modulation of inflammation to aid bone regeneration. However, the distance between exosomes and areas of damage can hinder efficient bone generation and cell survival. To overcome this limitation, we fabricated a continuous oxygen-supplying composite scaffold, with the encapsulation of calcium peroxide in a polylactic acid three-dimensional (3D) printing construct (CPS), as both an oxygen source and hydroxyapatite (HAP) precursor. Furthermore, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were incorporated into hyaluronic acid (HA) hydrogels to stimulate cell growth and modulate inflammation. The release of exosomes into cells leads to an increase in alkaline phosphatase production. In vivo results demonstrated that the composite scaffold regulated the inflammatory microenvironment, relieved tissue hypoxia, and promoted new bone formation. These results indicate that the synergistic effect of exosomes and oxygen promoted the proliferation of BMSCs, alleviated inflammation and exhibited excellent osteogenic properties. In conclusion, this osteogenic functional composite scaffold material offers a highly effective approach for bone repair.

Multiple-Effect Combined Hydrogels: "Temporal Regulation" Treatment of Osteosarcoma-Associated Bone Defects with Switchable Hyperthermia and Bioactive Agents.

Achieving the clinically staged treatment of osteosarcoma-associated bone defects encounters the multiple challenges of promptly removing postoperative residual tumor cells and bacterial infection, followed by bone reconstruction. Herein, a core/shell hydrogel with multiple-effect combination is designed to first exert antitumor and antibacterial activities and then promote osteogenesis. Specifically, doxorubicin (DOX) is loaded by magnesium-iron-based layered double hydroxide (LDH) to prepare LDOX, which is introduced into a thermo-sensitive hydrogel to serve as an outer shell of the core/shell hydrogel, meanwhile, LDH-contained liquid crystal hydrogel, abbreviated as LCgel-L, is served as an inner core. At the early stage of treatment, the dissociation of the outer shell triggered by moderate hyperthermia led to the thermo-sensitive release of LDOX, which can be targeted for the release of DOX within tumor cells, thereby promptly removing postoperative residual tumor cells based on the synergistic effect of photothermal therapy (PTT) and DOX, and postoperative bacterial infection can also be effectively prevented by PTT simultaneously. More importantly, the dissociation of the outer shell prompted the full exposure of the inner core, which will exert osteogenic activity based on the synergy of liquid crystal hydrogel as well as LDH-induced mild hyperthermia and ion effects, thereby enabling "temporal regulation" treatment of osteosarcoma-associated bone defects. This study provides a valuable insight for the development of osteosarcoma-associated bone repair materials.

Chitin whisker/chitosan liquid crystal hydrogel assisted scaffolds with bone-like ECM microenvironment for bone regeneration.

Natural bone exhibits a complex anisotropic and micro-nano hierarchical structure, more importantly, bone extracellular matrix (ECM) presents liquid crystal (LC) phase and viscoelastic characteristics, providing a unique microenvironment for guiding cell behavior and regulating osteogenesis. However, in bone tissue engineering scaffolds, the construction of bone-like ECM microenvironment with exquisite microstructure is still a great challenge. Here, we developed a novel polysaccharide LC hydrogel supported 3D printed poly(l-lactide) (PLLA) scaffold with bone-like ECM microenvironment and micro-nano aligned structure. First, we prepared a chitin whisker/chitosan polysaccharide LC precursor, and then infuse it into the pores of 3D printed PLLA scaffold, which was previously surface modified with a polydopamine layer. Next, the LC precursor was chemical cross-linked by genipin to form a hydrogel network with bone-like ECM viscoelasticity and LC phase in the scaffold. Subsequently, we performed directional freeze-casting on the composite scaffold to create oriented channels in the LC hydrogel. Finally, we soaked the composite scaffold in phytic acid to further physical cross-link the LC hydrogel through electrostatic interactions and impart antibacterial effects to the scaffold. The resultant biomimetic scaffold displays osteogenic activity, vascularization ability and antibacterial effect, and is expected to be a promising candidate for bone repair.

Synergistic effect of Mn-Si-COS on wound immune microenvironment by inhibiting excessive skin fibrosis mediated with ROS/TGF-ß1/Smad7 signal.

Excessive oxidative stress and inflammation often impede wound healing and ultimately lead to excessive skin fibrosis formation. It was known that the structural properties of biomaterials can affect the healing and immune response of surrounding tissues. In this work, a composite structure of Mn-Si-chitooligosaccharides (COS) was designed (COS@Mn-MSN) and the ability of regulating wound microenvironment for inhibiting skin fibrosis was investigated. In order to reduce the negative effects of Mn, the nano-level Mn was doped into MSN to minimize its content. The results show that Mn in COS@Mn-MSN showed significant ability of scavenging excess intracellular ROS within 1 d. The Si released from COS@Mn-MSN can shift M2 macrophage polarization in the later stage (1-3 d), showing anti-inflammatory effect. Macrophage (RAW264.7) were activated alternatively by COS released from COS@Mn-MSN, with upregulated expression of anti-inflammatory factors (IL-10 and CD206) and downregulated expression of pro-inflammatory factors (TNF-α, CD80, and IL-1ß) in the whole time. The expression of fibrosis associated factor TGF-ß1 and CD26 in fibroblast cells (L929) were inhibited by COS and Si. Besides, the inflammatory microenvironment mediated by COS@Mn-MSN downregulated Smad-7 gene expression and upregulated Col-1α gene expression. With the function of reducing oxidative stress (0-1 d), the TGF-ß1 inhibition (1-3 d) and anti-inflammatory effects (0-3 d), COS@Mn-MSN could inhibit excessive skin fibrosis formation mediated with ROS/TGF-ß1/Smad7 signal. Therefore, the prepared COS@Mn-MSN shows great potential to active scarless wound therapy.