Injectable nanofiber-reinforced bone cement with controlled biodegradability for minimally-invasive bone regeneration

Injectable materials show their special merits in regeneration of damaged/degenerated bones in minimally-invasive approach.Injectable calcium phosphate bone cement(CPC)has attracted broad attention for its bioactivity,as compared to non-degradable polymethyl methacrylate cement.However,its brittleness,poor anti-washout property and uncontrollable biodegradability are the main challenges to limit its further clinical application mainly because of its stone-like dense structure and fragile inorganic-salt weakness.Herein,we developed a kind of injectable CPC bone cement with porous structure and improved robustness by incorporating poly(lactide-co-glycolic acid)(PLGA)nanofiber into CPC,with carboxymethyl cellulose(CMC)to offer good injectability as well as anti-wash-out capacity.Furthermore,the introduction of PLGA and CMC also enabled a formation of initial porous structure in the cements,where PLGA nanofiber endowed the cement with a dynamically controllable biodegradability which provided room for cell movement and bone ingrowth.Inter-estingly,the reinforced biodegradable cement afforded a sustainable provision of Ca^(2+)bioactive components,together with its porous structure,to improve synergistically new bone formation and osteo-integration in vivo by using a rat model of femur condyle defect.Further study on regenerative mechanisms indicated that the good minimally-invasive bone regeneration may come from the synergistic enhanced osteogenic effect of calcium ion enrichment and the improved revascularization capacity contributed from the porosity as well as the lactic acid released from PLGA nanofiber.These results indicate the injectable bone cement with high strength,anti-washout property and controllable biodegradability is a promising candidate for bone regeneration in a minimally-invasive approach.

Size-transformable nanoparticles with sequentially triggered drug release and enhanced penetration for anticancer therapy

There are several limitations to the application of nanoparticles in the treatment of cancer,including their low drug loading,poor colloidal stability,insufficient tumor penetration,and uncontrolled release of the drug.Herein,gelatin/laponite(LP)/doxorubicin(GLD)nanoparticles are developed by crosslinking LP with gelatin for doxorubicin delivery.GLD shows high doxorubicin encapsulation efficacy(99%)and strong colloidal stability,as seen from the unchanged size over the past 21 days and reduced protein absorption by 48-fold compared with unmodified laponite/doxorubicin nanoparticles.When gelatin from 115 nm GLD reaches the tumor site,matrix metallopeptidase-2(MMP-2)from the tumor environment breaks it down to release smaller 40 nm LP nanoparticles for effective tumor cell endocytosis.As demonstrated by superior penetration in both in vitro three-dimensional(3D)tumor spheroids(138-fold increase compared to the free drug)and in vivo tumor models.The intracellular low pH and MMP-2 further cause doxorubicin release after endocytosis by tumor cells,leading to a higher inhibitory potential against cancer cells.The improved anticancer effectiveness and strong in vivo biocompatibility of GLD have been confirmed using a mouse tumor-bearing model.MMP-2/pH sequentially triggered anticancer drug delivery is made possible by the logical design of tumor-penetrating GLD,offering a useful method for anticancer therapy.

Incorporating redox-sensitive nanogels into bioabsorbable nanofibrous membrane to acquire ROS-balance capacity for skin regeneration

Facing the high incidence of skin diseases,it is urgent to develop functional materials with high bioactivity for wound healing,where reactive oxygen species(ROS)play an important role in the wound healing process mainly via adjustment of immune response and neovasculation.In this study,we developed a kind of bioabsorbable materials with ROS-mediation capacity for skin disease therapy.Firstly,redox-sensitive poly(N-isopropylacrylamide-acrylic acid)(PNA)nanogels were synthesized by radical emulsion polymerization method using a disulfide molecule as crosslinker.The resulting nanogels were then incorporated into the nanofibrous membrane of poly(L-lactic acid)(PLLA)via airbrushing approach to offer bioabsorbable membrane with redox-sensitive ROS-balance capacity.In vitro biological evaluation indicated that the PNA-contained bioabsorbable membrane improved cell adhesion and proliferation compared to the native PLLA membrane.In vivo study using mouse wound skin model demonstrated that PNA-doped nanofibrous membranes could promote the wound healing process,where the disulfide bonds in them were able to adjust the ROS level in the wound skin for mediation of redox potential to achieve higher wound healing efficacy.