Zn/Sr dual ions-collagen co-assembly hydroxyapatite enhances bone regeneration through procedural osteo-immunomodulation and osteogenesis

The immune microenvironment induced by biomaterials played vital roles in bone regeneration.Hydroxyapatite(HA)and its ion-substituted derivates represent a large class of core inorganic materials for bone tissue engineering.Although ion substitution was proved to be a potent way to grant HA more biological functions,few studies focused on the immunomodulatory properties of ion-doped HA.Herein,to explore the potential osteoimmunomodulatory effects of ion-doped HA,zinc and strontium co-assembled into HA through a collagen template biomimetic way(ZnSr-Col-HA)was successfully achieved.It was found that ZnSr-Col-HA could induce a favorable osteo-immune microenvironment by stimulating macrophages.Furthermore,ZnSr-Col-HA demonstrated a procedural promoting effect on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.Specifically,the osteo-immune microenvironment acted as a dominant factor in promoting osteogenic gene expressions at the early stage through OSM signal pathway.Whereas the direct stimulating effects on BMSCs by Zn^(2+)/Sr^(2+) were more effectively at the later stage with Nfatc1/Maf and Wnt signals activated.In vivo study confirmed strong promoting effects of ZnSr-Col-HA on critical-sized cranial defect repair.The current study indicated that such a combined biomaterial design philosophy of dual ion-doping and biomimetic molecular co-assembly to endow HA applicable osteoimmunomodulatory characteristics might bring up a new cutting-edge concept for bone regeneration study.

A comparative study of two porous sponge scaffolds prepared by collagen derived from porcine skin and fish scales as burn wound dressings in a rabbit model

Collagen is widely used in biomedical applications due to its outstanding properties.In this study,highly porous sponge scaffolds were developed by using porcine skin-derived collagen(PSC)and fish scale-derived collagen(FSC),respectively.The morphology and composition of these PSC and FSC scaffolds were compared.The water uptake ratio of FSC scaffolds reached 47.8,which is 1.7 times of PSC scaffolds.The water vapour transmission rates(WVTR)of PSC and FSC scaffolds were 952.6655.5 and 1090.9677.1 g/m2/day,which could produce a moist healing environment for wounds.Both scaffolds show non-toxicity to L929 fibroblast cells.The burn wound healing efficiency of these two scaffolds was examined in vivo using rabbits.No scars around the wounds were observed after applying PSC and SFC scaffolds.Histopathological studies reveal that the wound treated with PSC and FSC scaffolds showed much better wound recovery than gauze and vaseline gauze groups.It was suggested that FSC scaffolds have great potential as same as PSC to be used as burn wound dressing materials.

Synthesis and thermal stability of selenium-doped hydroxyapatite with different substitutions

Selenium （Se） plays a specific role in human health, especially for its anti- tumor effect. Incorporation of selenium into biocompatible hydroxyapatite （HAP） may endow the materials with novel characteristics. In the current work, a series of seleniumdoped hydroxyapatite （Se-HAP） nanoparticles with different SelP ratios were synthesized by a modified chemical precipitation. It was revealed that the powders with/without heattreatment were nano-sized needle-like HAP while the heat-treated samples have high crystallinity. The addition of selenium decreases the crystallinity of the synthesized apatite, and also takes a negative effect on the thermal stability of the as-prepared powders. The Se-HAP nanoparticles with Se/P molar ratio not more than 5% sintered at 900℃ can achieve good crystallinity and thermal stability.

Injectable bone cement with magnesium-containing microspheres enhances osteogenesis via anti-inflammatory immunoregulation

Injectable bone cement is especially useful in minimally invasive surgeries to repair small and irregular bone defects.Amongst different kinds of injectable bone cements,bioactive calcium phosphate bone cement(CPC)has been widely studied due to its biological activity.However,its dense structure and poor biodegradability prevent the ingrowth of living tissue,which leads to undesirable bone regeneration and clinical translation.To address this issue,we prepared bone cement based on Magnesium-containing microspheres(MMSs)that can not only be cured into a 3D porous scaffold but also have controllable biodegradability that continuously provides space for desired tissue ingrowth.Interestingly,magnesium ions released from MMSs cement(MMSC)trigger positive immunomodulation via upregulation of the anti-inflammatory genes IL-10 and M2 macrophage polarization with increased expression of CD206,which is beneficial to osteogenesis.Moreover,the physicochemical properties of MMSC,including heat release,rheology and setting time,can be tuned to meet the requirements of injectable bone cement for clinical application.Using a rat model,we have demonstrated that MMSC promoted osteogenesis via mediation of tissue ingrowth and anti-inflammatory immunomodulation.The study provides a paradigm for the design and preparation of injectable bone cements with 3D porous structures,biodegradability and anti-inflammatory immunoregulation to efficiently promote osteogenesis.

Si-doping bone composite based on protein template- mediated assembly for enhancing bone regeneration

Bio-inspired hybrid materials that contain organic and inorganic networks interpenetration at the molecular level have been a particular focus of interest on designing novel nanoscale composites. Here we firstly synthesized a series of hybrid bone composites, silicon-hydroxyapatites/silk fibroin/collagen, based on a specific molecular assembled strategy. Results of material characterization confirmed that silicate had been successfully doped into nano-hydroxyapatite lattice. In vitro evaluation at the cellular level clearly showed that these Si-doped composites were capable of promoting the adhesion and proliferation of rat mesenchymal stem cells （rMSCs）, extremely enhancing osteoblastic differentiation of rMSCs compared with silicon-free composite. More interestingly, we found there was a critical point of silicon content in the composition on regulating multiple cell behaviors. In vivo animal evaluation further demonstrated that Si-doped composites enabled to significantly improve the repair of cranial bone defect. Consequently, our current work not only suggests fabricating a potential bone repair materials by integrating element-doping and molecular assembled strategy in one system, but also paves a new way for constructing multi-functional composite materials in the future.

Silk fibroin/poly (vinyl alcohol) blend scaffolds for controlled delivery of curcumin

A silk fibroin/poly(vinyl alcohol)porous scaffold with a water vapor transmission rate of 21256464 g/m^(2)/day has been developed via thermally induced phase separation(gelation)and freeze-drying process.A hierarchical architecture of micropores and nanofibers was observed inside the scaffolds,and the related structures were analyzed.The viability and proliferation of 3T3 fibroblasts were examined,which indicated that the scaffolds exerted low cytotoxicity.After loading curcumin,the scaffolds can suppress the growth of 3T3 fibroblasts.The release behavior of curcumin from the scaffolds was investigated.At pH=7.2,the release profiles showed no significant difference for the loading amounts of 0.5mg and 0.25mg per sample.Meanwhile,the cumulative amount of released drug at pH=5.7 was significantly more than that in neutral solution due to more degradation of the scaffolds.It was suggested that the silk fibroin/poly(vinyl alcohol)blend scaffolds could be potentially used as wound dressing materials.

Albumin-assembled copper-bismuth bimetallic sulfide bioactive nanosphere as an amplifier of oxidative stress for enhanced radio-chemodynamic combination therapy

The tumor microenvironment with overexpressed hydrogen peroxide(H_(2)O_(2))and reinforced antioxidative system(glutathione,GSH)becomes a double-edged sword for the accessibility of nano-therapy.Since reactive oxygen species(ROS)are easily quenched by the developed antioxidative network,ROS-based treatments such as chemodynamic therapy(CDT)and radiotherapy(RT)for killing cancer cells are severely attenuated.To overcome such limitations,a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin(BSA)based bioactive nanospheres that are BSA assembled with in situ generated copper-bismuth sulfide nanodots and diallyl trisulfide(DATS).The copper-bismuth sulfide nanodots react with H_(2)O_(2)to produce·OH and release Cu^(2+).Then,the Cu^(2+)further depletes GSH to generate Cu^(+)for more·OH generation in the way of Fenton-like reaction.Such a cascade reaction can initiate·OH generation and GSH consumption to realize CDT.The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells.With the sensitization of increased oxidative stress and high Z element Bi,an enhanced radio-chemodynamic combination therapy is achieved.The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.

Frontiers in regenerative medical materials

Based on the last 10 successful series of the China–Korea Symposium on Biomaterials and Nano-biotechnology,we initiated a new invitation-based bilateral forum for established leaders and emerging young scientists in the field,the 2014 China–Korea symposium on biomimetic and regenerative medical materials,which was held from November 26 to 28 in Wuhan,China.In the past decade,a lot of breakthrough achievements in biomedical materials and regenerative medicine have been made in our two countries.Currently,biomaterials science and engineering has been evolved into a critical stage of bioactive integration and tissue regeneration from a simple functional replacement and substitution.Biomimetic and regenerative medical materials will become main topics in the field.