Changshun Ruan

Antibacterial effects and biocompatibility of titanium surfaces with graded silver incorporation in titania nanotubes.

Most commercial dental implants are made of titanium (Ti) because Ti possesses excellent properties such as osseointegration. However, many types of Ti products still suffer from insufficient antibacterial capability and bacterial infection after surgery remains one of the most common and intractable complications. In this study, a dual process encompassing anodization and silver plasma immersion ion implantation (Ag PIII) is utilized to produce titania nanotubes (TiO₂-NTs) containing Ag at different sites and depths. The concentration and depth of the incorporated Ag can be tailored readily by changing the PIII parameters. The Ag-embedded TiO₂-NTs which retain the nanotubular morphology are capable of sterilizing oral pathogens as opposed to pure Ti plates and pristine TiO₂-NTs. Biological assays indicate that the in vitro and in vivo biocompatibility of the sample plasma-implanted at a lower voltage of 0.5 kV (NT-Ag-0.5) is significantly compromised due to the large amount of surface Ag. On the other hand, the sample implanted at 1 kV (NT-Ag-1.0) exhibits unimpaired effects due to the smaller surface Ag accumulation. Sample NT-Ag-1.0 is further demonstrated to possess sustained antibacterial properties due to the large embedded depth of Ag and the technique and resulting materials have large potential in dental implants.

Adsorption force of fibronectin on various surface chemistries and its vital role in osteoblast adhesion.

The amount, type, and conformation of proteins adsorbed on an implanted biomaterial are believed to influence cell adhesion. Nevertheless, only a few research works have been dedicated to the contribution of protein adsorption force. To verify our hypothesis that the adsorption force of protein on biomaterial is another crucial mediator to cell adhesion, fibronectin (FN) adsorbed on self-assembled monolayers (SAMs) with terminal -OH, -CH3, and -NH2 was quantified for FN adsorption force (F(ad)) by utilizing a sphere/plane adsorption model and parallel plate flow chamber. As revealed, F(ad) on SAMs followed a chemistry-dependence of -NH2 > -CH3 ≫ -OH. It is further demonstrated that F(ad) together with FN conformation could regulate the late osteoblast adhesion and the consequent reorganization of the adsorbed FN and fibrillogenesis of the endogenous FN. Our study suggests that protein adsorption force plays a key role in cell adhesion and should be involved for better biomaterial design.

Bioabsorbable cellulose composites prepared by an improved mineral-binding process for bone defect repair

Bioabsorbable bacterial cellulose composites were prepared separately by immersing bacterial cellulose (BC) in different simulated body fluids (SBF) followed by incorporating cellulase enzymes into BC. The biomineralization of BC in SBF has been intensively documented and generally involves a tedious preparation. This study revealed an improved approach to disperse hydroxyapatite (HA) nanopowder to a saturated concentration (1.0×) of SBF, which was able to enhance the total amount of calcium phosphates (CPs) bound to BC composites. Such a simplified approach could be used to replace oversaturated concentration (1.5×) of SBF to prepare BC/CPs composites and achieve equal or even better material properties. The incorporation of cellulosic enzymes into BC/CPs composites verified the bioabsorption of BC where composites were able to achieve an in vitro bulk biodegradation with a yield of 96% glucose released. Cell culture of mouse osteoblasts also demonstrated the good biocompatibility of the BC/CPs composites prepared by using the simplified approach. This enzyme-incorporating BC/CPs composites studied show promise as bioabsorbable carriers delivering CPs for bone defect repair.

The efficient hemostatic effect of Antarctic krill chitosan is related to its hydration property

Antarctic krill chitosan (A-Chitosan) was first evaluated in its hemostatic effect in this study. The prepared A-Chitosan powder showed low level of crystallinity and significantly high water binding capacity as 1293% (w/w). By mice tail amputation model and blood coagulation timing experiment, it is showed that this chitosan accelerated the tail hemostasis by 55% and shortened the blood clotting time by 38%. This efficacy was better than two other commercial chitosans investigated and was corresponding to their water binding capacities. Through examining the effect of chitosan on blood components, it could be found that platelets adhesion was mainly affected by the water binding capacity, and red blood cells aggregation was dependent on their deacetylation degree. The physicochemical properties resulted in better hydration property of chitosan would improve its hemostatic effect. These results suggested that Antarctic krill chitosan is a good candidate for hemostatic application.

Synthesis, characterization, and biocompatibility of a novel biomimetic material based on MGF-Ct24E modified poly(D, L-lactic acid).

Mechano-growth factor (MGF) is an alternative splicing variant of Insulin-like growth factor I. MGF and its 24 amino acid peptide analog corresponding to the unique C-terminal E-domain (MGF-Ct24E) are the positive regulator for tissue regenesis in bone. A novel biomimetic poly(D, L-lactic acid) (PDLLA) modification was designed and synthesized based on MGF-Ct24E grafted maleic anhydride modified PDLLA (MPLA). MGF-Ct24Es were grafted into the side chain of MPLA via a stable covalent amide bond using 1-ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide as the condensing agent to produce biomimetic MPLA materials (MGF-Ct24E-MPLA). Fourier transform infrared spectrometry, amino acid analyzer, and elementary analysis were used to characterize the MGF-Ct24E-MPLA. The hydrophilicity of MGF-Ct24E-MPLA was evaluated by means of the water-uptake ratios and static water contact angle. Data revealed that the grafting efficiency of MGF-Ct24E was about 29.9%. MGF-Ct24E-MPLA had better hydrophilicity than PDLLA and MPLA. The osteoblasts behavior of proliferation, differentiation, and mineralization on PDLLA, MPLA, and MGF-Ct24E-MPLA films was investigated and the results indicated that the introduction of MGF-Ct24E could improve osteoblasts proliferation, mineralization, and delay differentiation. The MGF-Ct24E modified MPLA with higher bioactivity may have potential application for bone tissue engineering.

Stretching-induced nanostructures on shape memory polyurethane films and their regulation to osteoblasts morphology.

Programming such as stretching, compression and bending is indispensible to endow polyurethanes with shape memory effects. Despite extensive investigations on the contributions of programming processes to the shape memory effects of polyurethane, less attention has been paid to the nanostructures of shape memory polyurethanes surface during the programming process. Here we found that stretching could induce the reassembly of hard domains and thereby change the nanostructures on the film surfaces with dependence on the stretching ratios (0%, 50%, 100%, and 200%). In as-cast polyurethane films, hard segments sequentially assembled into nano-scale hard domains, round or fibrillar islands, and fibrillar apophyses. Upon stretching, the islands packed along the stretching axis to form reoriented fibrillar apophyses along the stretching direction. Stretching only changed the chemical patterns on polyurethane films without significantly altering surface roughness, with the primary composition of fibrillar apophyses being hydrophilic hard domains. Further analysis of osteoblasts morphology revealed that the focal adhesion formation and osteoblasts orientation were in accordance with the chemical patterns of the underlying stretched films, which corroborates the vital roles of stretching-induced nanostructures in regulating osteoblasts morphology. These novel findings suggest that programming might hold great potential for patterning polyurethane surfaces so as to direct cellular behavior. In addition, this work lays groundwork for guiding the programming of shape memory polyurethanes to produce appropriate nanostructures for predetermined medical applications.

Black-Phosphorus-Incorporated Hydrogel as a Sprayable and Biodegradable Photothermal Platform for Postsurgical Treatment of Cancer

Abstract Photothermal therapy (PTT) is a fledgling therapeutic strategy for cancer treatment with minimal invasiveness but clinical adoption has been stifled by concerns such as insufficient biodegradability of the PTT agents and lack of an efficient delivery system. Here, black phosphorus (BP) nanosheets are incorporated with a thermosensitive hydrogel [poly(d,l‐lactide)‐poly(ethylene glycol)‐poly(d,l‐lactide) (PDLLA‐PEG‐PDLLA: PLEL)] to produce a new PTT system for postoperative treatment of cancer. The BP@PLEL hydrogel exhibits excellent near infrared (NIR) photothermal performance and a rapid NIR‐induced sol–gel transition as well as good biodegradability and biocompatibility in vitro and in vivo. Based on these merits, an in vivo PTT postoperative treatment strategy is established. Under NIR irradiation, the sprayed BP@PLEL hydrogel enables rapid gelation forming a gelled membrane on wounds and offers high PTT efficacy to eliminate residual tumor tissues after tumor removal surgery. Furthermore, the good photothermal antibacterial performance prevents infection and this efficient and biodegradable PTT system is very promising in postoperative treatment of cancer.

Incorporating isosorbide as the chain extender improves mechanical properties of linear biodegradable polyurethanes as potential bone regeneration materials

One key limitation to the application of linear biodegradable polyurethanes (LBPUs) in scaffold materials for bone regeneration is their insufficient mechanical properties. In this study, isosorbide (ISO), a rigid two-ring small diol is selected as a chain extender to produce a series of new poly (D,L-lactide)-based polyurethanes (ISO-PUs). It is confirmed that incorporating ISO as the chain extender can significantly reduce the crosslinking degree of ISO-PUs and thus increase their molecular weight and mechanical properties. ISO-PUs with Mn values of 72.09 kDa and 84.79 kDa demonstrate higher tensile strength & modulus (39.87 MPa & 2.19 GPa and 42.68 MPa & 2.57 GPa) than PDLLA with a Mn of 100 kDa (36.15 MPa & 2.07 GPa). All these results, together with the sound cytocompatibility of ISO-PUs with MC3T3-E1 cells based on the morphology observation and cell proliferation, suggest that ISO-PU should be a promising scaffold material for bone regeneration.

Enhanced osteointegration of poly(methylmethacrylate) bone cements by incorporating strontium-containing borate bioactive glass

Although poly(methylmethacrylate) (PMMA) cements are widely used in orthopaedics, they have numerous drawbacks. This study aimed to improve their bioactivity and osseointegration by incorporating strontium-containing borate bioactive glass (SrBG) as the reinforcement phase and bioactive filler of PMMA cement. The prepared SrBG/PMMA composite cements showed significantly decreased polymerization temperature when compared with PMMA and retained properties of appropriate setting time and high mechanical strength. The bioactivity of SrBG/PMMA composite cements was confirmed in vitro, evidenced by ion release (Ca, P, B and Sr) from SrBG particles. The cellular responses of MC3T3-E1 cells in vitro demonstrated that SrBG incorporation could promote adhesion, migration, proliferation and collagen secretion of cells. Furthermore, our in vivo investigation revealed that SrBG/PMMA composite cements presented better osseointegration than PMMA bone cement. SrBG in the composite cement could stimulate new-bone formation around the interface between the composite cement and host bone at eight and 12 weeks post-implantation, whereas PMMA bone cement only stimulated development of an intervening connective tissue layer. Consequently, the SrBG/PMMA composite cement may be a better alternative to PMMA cement in clinical applications and has promising orthopaedic applications by minimal invasive surgery.

Strontium incorporation improves the bone-forming ability of scaffolds derived from porcine bone

Although heterogeneous bone scaffolds have shown potential in bone defect repair, their capability of aiding bone regeneration need to be further enhanced. Strontium, one important trace element in bone, has a well-known favorable effect on bone repair. Here a strontium containing scaffold (CPB/PCL/Sr) based on superficially porous calcined porcine bone (CPB) was obtained straightforwardly by sequential coating of SrCl2 and polycaprolactone (PCL). The basic characterization revealed that PCL coating could simultaneously improve the mechanical properties and, more importantly, restrain strontium release. Moreover, in vitro behaviors of human MSCs on CPB, CPB/PCL, and CPB/PCL/Sr were studied in detail. The comprehensive results of proliferation, osteogenic gene expression, ALP staining, and ALP activity demonstrated that PCL coating slightly impaired the bone repair potential of CPB. In contrast, CPB/PCL/Sr better supported the osteogenic differentiation of MSCs than CPB，highlighting the role of strontium. The in vivo test confirmed a better new bone formation of CPB/PCL/Sr than CPB and CPB/PCL. These results verified the superiority of incorporating strontium to improve the bone-forming ability of CPB, offering a promising alternative for bone defect repair.