Fibrous dressing containing bioactive glass with combined chemotherapy and wound healing promotion for post-surgical treatment of melanoma.

Surgery is the mainstream treatment for melanoma. However, inappropriate post-surgical treatment could result in the tumor recurrence and sever tissue damage, which ultimately leads to the failure of therapy and significantly compromises the therapeutic outcome of surgery. Herein, taking advantages of the co-axial electrospinning technology, we construct a dual-function nanofibrous wound dressing for the post-surgical treatment of melanoma. Si-Ca-P-based mesoporous bioactive glass (MBG) was prepared by the template-sol-gel process, with the compositions being set as 60 SiO2: 36 CaO: 4 P2O5 in mol%. Through rational design, 5-fluorouracil (5-FU)-loaded MBG nanoparticles (MBG-U) are successfully incorporated into the fiber core with biodegradable poly(lactic-co-glycolic acid) (PLGA) as the cladding layer to form the core-shell nanofibers (MBG-U CSF), which achieves sustained releases of chemotherapeutic drug (i.e.,5-FU) and wound healing promotion function. Thereafter, the post-surgical melanoma model was established to evaluate the in-situ anti-cancer and wound healing effect of MBG-U CSF. Thereafter, the post-surgical melanoma model was established to evaluate the anti-cancer and wound healing effect. The results demonstrated that the core-shell nanofibrous dressing almost complete suppressed tumor growth, and simultaneously promoted skin regeneration, which provides a promising strategy for the post-surgical treatment for melanoma.

Integrated Piezoelectric/Conductive Composite Cryogel Creates Electroactive Microenvironment for Enhanced Bone Regeneration.

Natural bone tissue possesses inherent electrophysiological characteristics, displaying conductivity and piezoelectricity simultaneously; hence, the reconstruction of local electrical microenvironment at defect site provides an effective strategy to enhance osteogenesis. Herein, a composite cryogel-type scaffold (referred to as Gel-PD-CMBT) is developed for bone regeneration, utilizing gelatin (Gel) in combination with a conductive poly(ethylene dioxythiophene)/polystyrene sulfonate matrix and Ca/Mn co-doped barium titanate (CMBT) nanofibers as the piezoelectric filler. The incorporation of these components results in the formation of an integrated piezoelectric/conductive network within the scaffold, facilitating charge migration and yielding a conductivity of 0.59 S cm-1 . This conductive scaffold creates a promising electroactive microenvironment, which is capable of up-regulating biological responses. Furthermore, the interconnected porous structure of the Gel-PD-CMBT scaffold not only provides mechanical stability but also offered ample space for cellular and tissue ingrowth. This Gel-PD-CMBT scaffold demonstrates a greater capacity to promote cellular osteogenic differentiation in vitro and neo-bone formation in vivo. In summary, the Gel-PD-CMBT scaffold, with its integrated piezoelectricity and conductivity, effectively restores the local electroactive microenvironment, offering an ideal platform for the regeneration of electrophysiological bone tissue.

A biomimetic piezoelectric scaffold with sustained Mg2+ release promotes neurogenic and angiogenic differentiation for enhanced bone regeneration.

Natural bone is a composite tissue made of organic and inorganic components, showing piezoelectricity. Whitlockite (WH), which is a natural magnesium-containing calcium phosphate, has attracted great attention in bone formation recently due to its unique piezoelectric property after sintering treatment and sustained release of magnesium ion (Mg2+). Herein, a composite scaffold (denoted as PWH scaffold) composed of piezoelectric WH (PWH) and poly(ε-caprolactone) (PCL) was 3D printed to meet the physiological demands for the regeneration of neuro-vascularized bone tissue, namely, providing endogenous electric field at the defect site. The sustained release of Mg2+ from the PWH scaffold, displaying multiple biological activities, and thus exhibits a strong synergistic effect with the piezoelectricity on inhibiting osteoclast activation, promoting the neurogenic, angiogenic, and osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) in vitro. In a rat calvarial defect model, this PWH scaffold is remarkably conducive to efficient neo-bone formation with rich neurogenic and angiogenic expressions. Overall, this study presents the first example of biomimetic piezoelectric scaffold with sustained Mg2+ release for promoting the regeneration of neuro-vascularized bone tissue in vivo, which offers new insights for regenerative medicine.

Injectable, High Specific Surface Area Cryogel Microscaffolds Integrated with Osteoinductive Bioceramic Fibers for Enhanced Bone Regeneration.

Organic-inorganic composites with high specific surface area and osteoinductivity provide a suitable microenvironment for cell ingrowth and effective ossification, which could greatly promote bone regeneration. Here, we report gelatin methacryloyl (GelMA) cryogel microspheres that are reinforced with hydroxyapatite (HA) nanowires and calcium silicate (CS) nanofibers to achieve the goal. The prepared composite cryogel microspheres with open porous structure and rough surface greatly facilitate cell anchoring, simultaneously exhibiting excellent injectability. Compared to the only HA- or CS-containing counterparts, the GelMA cryogel microspheres composited with HA:CS (termed as GMHC) achieve sustained release of bioactive Ca, P, and Si elements, which are conducive to osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). These composite microspheres can prevent from forming peralkalic conditions, which is beneficial for cell growth. After injection of cryogel microspheres into rat calvarial defects, neo-bone tissue grows into their pores, showing tight integration. The embedded bioceramic components significantly promote bone regeneration, with the GMHC achieving the best regenerative outcomes. Promisingly, porous organic-inorganic composite cryogel microspheres, with high specific surface area, biodegradability, and osteoinductivity, can act as injectable microscaffolds to repair bone defects with enhanced efficiency, which may widen the scaffold strategy for bone tissue engineering.

Dental resin composites with improved antibacterial and mineralization properties via incorporating zinc/strontium-doped hydroxyapatite as functional fillers.

This study intends to improve the antibacterial and mineralization performance of photocurable dental resin composites (DRCs) to reduce the possibility of repair failure caused by secondary caries. To the end, functionalized hydroxyapatite (HAp), including Zn-doped (Zn/HAp) and Sr-doped HAp (Sr/HAp), were added into the bisphenol A glycidyl methacrylate and triethylene glycol dimethacrylate mixture, providing the DRCs with antibacterial and mineralization capacity, respectively. By controlling the total amount of inorganic filler at 70 wt%, these HAp powders were introduced into the resin matrix with barium glass powder (BaGP), while the ratios of HAp to aGP varied from 0:70 to 8:62. And the 8 wt% of HAp could be pure HAp, Zn/HAp, Sr/HAp, or Zn/HAp +Sr/HAp in different ratios (i.e. 2:6, 4:4, 6:2). Though the fillers varied, the obtained DRCs displayed similar micro-morphology, flexural strength (∼110 MPa) and modulus (∼7 GPa), and Vickers hardness (∼65). When the doping amounts of Sr2+/Zn2+reached 15 mol% of Ca2+in the Sr/HAp and Zn/HAp, the DRCs displayed a high antibacterial activity by killing ∼95%Staphylococcus aureus, and induced rich mineral deposition on surface in simulated body fluid. The incorporation of the Zn/HAp and Sr/HAp into the DRCs did not cause significant cytotoxicity, with L929 fibroblasts remaining >99% viability as cultured in extracts made from the DRCs. Therein, the DRC preparations containing both Zn/HAp and Sr/HAp have achieved improvements in both the biomineralization and antibacterial performance, as well as, having sufficient mechanical properties and excellent biocompatibility for dental restoration.

Improving antibacterial performance of dental resin adhesive via co-incorporating fluoride and quaternary ammonium.

OBJECTIVE: Aiming to achieve improved antibacterial performance for dental application, sodium fluoride (NaF) nanoparticles and photopolymerizable N,N-dodecylvinylimidazole (DCV) were co-introduced into the dental resin adhesive at different ratios. METHODS: The respective effect of NaF and DCV on adhesive curing kinetic, antibacterial activities against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Bacterial Flora of Human saliva (HSBF) were comprehensively evaluated. Then, the synergistic effects of NaF nanoparticles and DCV on adhesive performance were studied in terms of fluoride ion (F-) release, antibacterial activity, hydrophilicity, surface potential, cytotoxicity, and bonding strength. RESULTS: DCV monomer could polymerize with other adhesive monomers without influencing C = C double conversion rate, while the addition amount of DCV would affect the hydrophilicity and bonding strength of the cured adhesives. The cationic quaternary ammonium group could reduce the burst release of negative F- for the adhesive at a NaF/DCV ratio (1:1, 2%), hence achieving both non-contact and contact antibacterial activity in an extended term without causing cytotoxicity. CONCLUSION: Mixing NaF nanoparticles and DCV into the dental resin adhesive can slow down the initial burst release of F- and prolong the release-type antibacterial effect. The ionic interaction between F- and quaternary ammonium groups, as well as, the effect of DCV on adhesive hydrophilicity, simultaneously influence the release behavior of F-. Co-incorporation of quanternary ammonium and fluoride improves adhesive's antibacterial performance for dental application. CLINICAL SIGNIFICANCE: Incorporating both NaF nanoparticles and DCV into dental resin adhesive could provide an efficient strategy for dental restoration as well as the prevention of secondary caries.

In vitroandin vivoevaluation of biomimetic hydroxyapatite/whitlockite inorganic scaffolds for bone tissue regeneration.

Native bone tissue can be formed by developing collagen fibrils coated with hydroxyapatite (HA) and whitlockite (WH) nanoparticles after mineralization. WH has attracted much attention as the second most abundant bone mineral in human bones. It has a negatively charged surface, which can adsorb osteogenesis-related proteins such as bone sialoproteinin vivo, thus having a stronger possibility to induce osteogenesis. However, due to its poor thermodynamic stability and intermediate phases, the preparation of WH is relatively tricky, so WH inorganic scaffolds are still rarely studied. Therefore, this study explored the preparation of WH inorganic scaffolds using the hydrothermal method and prepared pure inorganic WH scaffolds. The prepared scaffolds exhibited apparent WH crystal phases in the x-ray powder diffraction (XRD) characterization. In the scanning electron microscopy (SEM) images, the WH scaffolds had an apparent hexagonal crystal form, which had a pronounced effect on promoting cell proliferation and differentiationin vitroexperiments compared to the HA and HA/WH scaffolds. Furthermore, the scaffolds were used to verify the osteogenic properties of subcutaneous ectopic osteogenesis or repair of the calvarial defectin vivoand proved that the WH inorganic scaffolds have an excellent synergistic osteogenic ability.

Self-reinforcement hydrogel with sustainable oxygen-supply for enhanced cell ingrowth and potential tissue regeneration.

Hydrogels composed of natural biopolymers are attractive for tissue regeneration applications owing to their advantages such as biocompatibility and ease of administration, etc.. Yet, the low oxygen level and the crosslinked network inside bulk hydrogels, as well as the hypoxic status in defect areas, hamper cell viability, function, and eventual tissue repair. Herein, based on Ca2+-crosslinked alginate hydrogel, oxygen-generating calcium peroxide (CaO2) was introduced, which could provide a dynamic crosslinking alongside the CaO2 decomposition. Compared to the CaCl2-crosslinked alginate hydrogel, bone marrow mesenchymal stromal cells cultured with CaO2-contained system displayed remarkably improved biological behaviors. Furthermore, in vivo evaluations were carried out on a subcutaneous implantation in rats, and the results demonstrated the importance of the local oxygen availability in a series of crucial events for tissue regeneration, such as activating cell viability, migration, angiogenesis, and osteogenesis. In summary, the obtained Ca2+-crosslinked alginate hydrogel achieved a better microenvironment for cell ingrowth and potential tissue regeneration as the CaCl2 crosslinker being replaced by oxygen-generating CaO2 nanoparticles, due to its contribution in remedying the local hypoxic condition, promisingly, the release of Ca2+ makes the hydrogel to be a possible candidate scaffold for bone tissue engineering.