A combination therapy for androgenic alopecia based on quercetin and zinc/copper dual-doped mesoporous silica nanocomposite microneedle patch.

A nanocomposite microneedle (ZCQ/MN) patch containing copper/zinc dual-doped mesoporous silica nanoparticles loaded with quercetin (ZCQ) was developed as a combination therapy for androgenic alopecia (AGA). The degradable microneedle gradually dissolves after penetration into the skin and releases the ZCQ nanoparticles. ZCQ nanoparticles release quercetin (Qu), copper (Cu2+) and zinc ions (Zn2+) subcutaneously to synergistically promote hair follicle regeneration. The mechanism of promoting hair follicle regeneration mainly includes the regulation of the main pathophysiological phenomena of AGA such as inhibition of dihydrotestosterone, inhibition of inflammation, promotion of angiogenesis and activation of hair follicle stem cells by the combination of Cu2+ and Zn2+ ions and Qu. This study demonstrates that the systematic intervention targeting different pathophysiological links of AGA by the combination of organic drug and bioactive metal ions is an effective treatment strategy for hair loss, which provides a theoretical basis for development of biomaterial based anti-hair loss therapy.

A novel "hot spring"-mimetic hydrogel with excellent angiogenic properties for chronic wound healing.

The treatment of chronic wounds is a major challenge in regenerative medicine, and angiogenesis is known to be critical for chronic wound healing. Hot springs with temperature in the range of 30-45 °C can promote blood circulation, and some hot spring elements including iron and silicon are also known to be active in promoting angiogenesis. Inspired by the hot spring function, we designed a novel bioactive photothermal hydrogel with "hot spring effect" based on fayalite (FA) and N, O-carboxymethyl chitosan (NOCS), which releases bioactive ions and has heating function to create hot ion environment in wound area. The hot spring-mimetic hydrogel showed significant enhancement of angiogenesis and chronic wound healing in vivo due to the in situ heating through photothermal effect combined with the bioactive ions (Fe2+ and SiO44-) released from the hydrogel. It is further confirmed that the synergetic effect of the mild heating and bioactive ions on angiogenesis was mainly because of the activation of different angiogenic factors and signaling pathways. Our study suggests that the hot spring-mimetic approach may be an effective strategy to design bioactive materials for promoting angiogenesis and tissue regeneration.

Design of a biofluid-absorbing bioactive sandwich-structured Zn-Si bioceramic composite wound dressing for hair follicle regeneration and skin burn wound healing.

The deep burn skin injures usually severely damage the dermis with the loss of hair follicle loss, which are difficult to regenerate. Furthermore, severe burns often accompanied with large amount of wound exudates making the wound moist, easily infected, and difficult to heal. Therefore, it is of great clinical significance to develop wound dressings to remove wound exudates and promote hair follicle regeneration. In this study, a sandwich-structured wound dressing (SWD) with Janus membrane property was fabricated by hot compression molding using hydrophilic zinc silicate bioceramics (Hardystonite, ZnCS) and hydrophobic polylactic acid (PLA). This unique organic/inorganic Janus membrane structure revealed excellent exudate absorption property and effectively created a dry wound environment. Meanwhile, the incorporation of ZnCS bioceramic particles endowed the dressing with the bioactivity to promote hair follicle regeneration and wound healing through the release of Zn2+ and SiO3 2- ions, and this bioactivity of the wound dressing is mainly attributed to the synergistic effect of Zn2+ and SiO3 2- to promote the recruitment, viability, and differentiation of hair follicle cells. Our study demonstrates that the utilization of the Janus membrane and synergistic effect of different type bioactive ions are effective approaches for the design of wound dressings for burn wound healing.

PDA/Cu Bioactive Hydrogel with "Hot Ions Effect" for Inhibition of Drug-Resistant Bacteria and Enhancement of Infectious Skin Wound Healing.

Quick and effective sterilization of drug-resistant bacteria inevitably became an ever-growing global challenge. In this study, a multifunctional composite (PDA/Cu-CS) hydrogel mainly composed of polydopamine (PDA) and copper-doped calcium silicate ceramic (Cu-CS) was prepared. It was confirmed that PDA/copper (PDA/Cu) complexing in the composite hydrogel played a key role in enhancing the photothermal performance and antibacterial activity. Through a unique "hot ions effect", created by the heating of Cu ions through the photothermal effect of the composite hydrogel, the hydrogel showed high-efficiency, quick, and long-term inhibition of methicillin-resistant Staphylococcus aureus and Escherichia coli. In addition, the hydrogel possessed remarkable bioactivity to stimulate angiogenesis. The in vivo results confirmed that the "hot ions effect" of the composite hydrogel removed existing infection in the wound area efficiently and significantly promoted angiogenesis and collagen deposition during infectious skin wound healing. Our results suggested that the design of multifunctional hydrogels with "hot ions effect" may be an effective therapeutic approach for the treatment of infectious wounds.

Design of a Multifunctional Biomaterial Inspired by Ancient Chinese Medicine for Hair Regeneration in Burned Skin.

In deep burn injuries, the dermis of the skin is often severely damaged, and hair follicles are also lost and lose the potential for regeneration. Therefore, the development of wound dressings that promote hair follicle regeneration has important clinical significance. In this study, inspired by an ancient Chinese medicine prescription, a novel fibrous membrane (P/Qu/Cup; P, PCL; Qu, quercetin; Cup, cuprorivaite, CaCuSi4O10) containing quercetin-copper (Qu-Cu) chelates was fabricated by using quercetin and a highly bioactive bioceramic (CaCuSi4O10) incorporated in PCL/gelatin electrospun fibers. The fibrous membrane can effectively release Qu and Cu ions to induce proliferation, migration, and differentiation of skin and hair follicle related cells, and the Qu, Cu ions, and Si ions released from the composite membrane revealed synergistic activity to stimulate hair follicle regeneration and wound healing. Our study demonstrated that the analysis of the common components in ancient Chinese prescription is an effective approach to design novel bioactive materials for regenerative medicine.

Bioinspired multifunctional biomaterials with hierarchical microstructure for wound dressing.

Developing multifunctional wound dressing with desired mechanical strength is of great significance for the treatment of different types of skin wounds. Inspired by the close relationship between strength and hierarchical structure of nacre, hierarchical and porous graphene oxide-chitosan-calcium silicate (GO-CTS-CS) film biomaterials are fabricated by a combination of vacuum filtration-assisted assembly and freeze-drying methods. The bioinspired hierarchical materials emulate an orderly porous lamellar micron-scale structure and the "brick-and-mortar"-layered nanostructure. The hierarchical microstructure endows the GO-CTS-CS biomaterials with good tensile strength, compatible breathability, and water absorption. Furthermore, the hierarchical GO-CTS-CS biomaterials exhibit ideal photothermal performance, leading to significant photothermal antibacterial and antitumor efficacy. Further, the hierarchical GO-CTS-CS biomaterials show stimulatory effect on in vivo chronic wound healing. Therefore, such a high performance and multifunctional biomaterial is believed to offer a promising alternative to traditional wound dressing in future. STATEMENT OF SIGNIFICANCE: Although it is an effective strategy to prepare high-performance materials by mimicking the hierarchical microstructure of nacre, the preparation of nacre-inspired materials in tissue engineering fields still needs to be investigated. In this work, we prepared a nacre-inspired multifunctional graphene oxide-chitosan-calcium silicate (GO-CTS-CS) biomaterial with a hierarchical microstructure. The hierarchical microstructure endows the biomaterials with desired properties of strength, breathability, and water absorption. Further, the hierarchical GO-CTS-CS biomaterial showed good photothermal antibacterial/antitumor and wound healing effects. This work may provide an approach to combine the preparation of multifunctional biomaterials with bioinspired engineering by constructing a hierarchical microstructure, indicating that the assembling hierarchical microstructure in biomaterials is of great importance for tissue engineering and regenerative medicine.

Multifunctional Zn doped hollow mesoporous silica/polycaprolactone electrospun membranes with enhanced hair follicle regeneration and antibacterial activity for wound healing.

Due to the complexity of the skin tissue structure, the regeneration of the entire skin, including skin appendages such as hair follicles, is a big challenge. In addition, skin trauma is often accompanied by bacterial infections that delay the wound healing. Therefore, developing wound dressings, which promote hair follicle regeneration and inhibit bacterial infection in the wound healing process, is of great clinical significance. In this study, Zn doped hollow mesoporous silica nanospheres (HMZS) were synthesized by a sol-gel method and a novel wound healing dressing was prepared by incorporation of drug ciprofloxacin hydrochloride (CiH)-loaded Zn containing mesoporous silica nanospheres (CiH-HMZS) into polycaprolactone (PCL) electrospun fibers. The CiH-HMZS/P nano-composite electrospun fibers exhibit the ability to promote angiogenesis and skin regeneration by releasing Si ions, and the activity to enhance hair follicle regeneration and inhibit bacterial growth by releasing zinc ions and achieve the synergistic antibacterial effect with both Zn ions and CiH in low concentrations. Thus, the CiH-HMZS/P nano-composite membrane is a promising multi-functional wound healing material for inhibiting bacterial growth in infected wounds and enhancing skin wound healing including hair follicle regeneration.

Bone tissue engineering strategy based on the synergistic effects of silicon and strontium ions.

Multipotent human bone marrow mesenchymal stem cells (hBMSCs) are commonly used as seed cells in bone tissue engineering, but their clinical application is limited due to two challenges. One is the expansion of hBMSCs without loss of the stemness, and the other is the stimulation of osteogenic differentiation of hBMSCs when combined with biomaterials. In this study we demonstrated an approach by firstly elucidating the functional effects and optimal concentrations of Si and Sr ions on the proliferation and osteogenic differentiation of hBMSCs, and then designing bioactive bioceramic/alginate hydrogels which could release Si and Sr bioactive ions in the same optimal concentrations range for activation of the cells in vivo. The results showed that Si and Sr ions could synergistically stimulate cell proliferation without losing the stemness. Furthermore, at higher concentrations, Si and Sr ions stimulated osteogenic differentiation instead of enhancing proliferation. The designed bioactive hydrogels revealed activity to stimulate not only the osteogenic differentiation of encapsulated hBMSCs, but also the blood vessel formation in vivo. These results suggested that the design of biomaterials based on the biological function of different material elements was an effective approach for bone tissue engineering applications. STATEMENT OF SIGNIFICANCE: The clinical application of multipotent human bone marrow mesenchymal stem cells (hBMSCs) in bone tissue engineering is limited due to two challenges. One is the expansion of cells without loss of the stemness, and the other is the stimulation of osteogenic differentiation of hBMSCs within the biomaterial scaffolds. Herein, we demonstrated an approach by firstly elucidating the functional effects and optimal concentrations of Si and Sr ions on the proliferation without losing stemness and osteogenic differentiation of hBMSCs, and then designing a bioactive bioceramic/alginate hydrogel which could release Si and Sr ions for in vivo activation of cells. The bioactive hydrogels revealed activity to stimulate not only osteogenic differentiation of encapsulated hBMSCs, but also the blood vessel formation in vivo. Our work provided an effective approach to design effective biomaterials for tissue engineering.

Single polymer growth dynamics.

In chain-growth polymerization, a chain grows continually to reach thousands of subunits. However, the real-time dynamics of chain growth remains unknown. Using magnetic tweezers, we visualized real-time polymer growth at the single-polymer level. Focusing on ring-opening metathesis polymerization, we found that the extension of a growing polymer under a pulling force does not increase continuously but exhibits wait-and-jump steps. These steps are attributable to the formation and unraveling of conformational entanglements from newly incorporated monomers, whose key features can be recapitulated with molecular dynamics simulations. The configurations of these entanglements appear to play a key role in determining the polymerization rates and the dispersion among individual polymers.