Chang Yao

Enhanced osteoblast adhesion to drug-coated anodized nanotubular titanium surfaces.

Current orthopedic implants have functional lifetimes of only 10–15 years due to a variety of reasons including infection, extensive inflammation, and overall poor osseointegration (or a lack of prolonged bonding of the implant to juxtaposed bone). To improve properties of titanium for orthopedic applications, this study anodized and subsequently coated titanium with drugs known to reduce infection (penicillin/streptomycin) and inflammation (dexamethasone) using simple physical adsorption and the deposition of such drugs from simulated body fluid (SBF). Results showed improved drug elution from anodized nanotubular titanium when drugs were coated in the presence of SBF for up to 3 days. For the first time, results also showed that the simple physical adsorption of both penicillin/streptomycin and dexamethasone on anodized nanotubular titanium improved osteoblast numbers after 2 days of culture compared to uncoated unanodized titanium. In addition, results showed that depositing such drugs in SBF on anodized titanium was a more efficient method to promote osteoblast numbers compared to physical adsorption for up to 2 days of culture. In addition, osteoblast numbers increased on anodized titanium coated with drugs in SBF for up to 2 days of culture compared to unanodized titanium. In summary, compared to unanodized titanium, this preliminary study provided unexpected evidence of greater osteoblast numbers on anodized titanium coated with either penicillin/streptomycin or dexamethasone using simple physical adsorption or when coated with SBF; results which suggest the need for further research on anodized titanium orthopedic implants possessing drug-eluting nanotubes.

Prolonged antibiotic delivery from anodized nanotubular titanium using a co-precipitation drug loading method.

Advances in nanotechnology have led to the development of novel orthopedic implant materials that not only have better cytocompatibility properties but can also be used as unique drug delivery platforms. In the present study, currently used titanium was anodized to possess nanotubular surface structures (80 nm inner diameter and 200 nm deep) capable of drug delivery. Such anodized nanotubular titanium surfaces promote bone cell functions (such as adhesion and differentiation) in vitro and in vivo compared with unanodized titanium. To achieve local drug delivery, anodized titanium with nanotubular structures were loaded with penicillin-based antibiotics using a co-precipitation method in which drug molecules were mixed in simulated body fluid to collectively precipitate with calcium phosphate crystals. Results showed for the first time that such co-precipitated coatings on anodized nanotubular titanium could release drug molecules for up to 3 weeks whereas previous studies have demonstrated only a 150-minute release of antibiotics through simple physical adsorption. Furthermore, drug release using co-precipitation from anodized nanotubular titanium was determined to be a diffusion process dependent on first-order kinetics. In addition, contrary to conventional thinking that penicillin-based drug release should decrease cell functions (including both bacteria and mammalian cells), results of this study showed similar osteoblast (bone-forming cell) adhesion between non-drug loaded and drug loaded precipitated calcium phosphate coatings on anodized titanium. Due to the above, these findings represent a promising surface treatment for titanium that could be used for local drug delivery for improving orthopedic applications and, thus, should be studied further.

Increased chondrocyte adhesion on nanotubular anodized titanium.

Previous studies have demonstrated increased osteoblast (bone-forming cells) functions (including adhesion, synthesis of intracellular collagen, alkaline phosphatase activity, and deposition of calcium-containing minerals) on titanium anodized to possess nanometer features compared with their unanodized counterparts. Such titanium materials were anodized to possess novel nanotubes also capable of drug delivery. Since titanium has not only experienced wide spread commercial use in orthopedic but also in cartilage applications, the objective of the present in vitro study was for the first time to investigate chondrocyte (cartilage synthesizing cells) functions on titanium anodized to possess nanotubes. For this purpose, titanium was anodized in dilute hydrofluoric acid at 20 V for 20 min. Results showed increased chondrocyte adhesion on anodized titanium with nanotube structures compared with unanodized titanium. Importantly, the present study also provided evidence why. Since material characterization studies revealed significantly greater nanometer roughness and similar chemistry as well as crystallinity between nanotubular anodized and unanodized titanium, the results of the present study highlight the importance of the nanometer roughness provided by anodized nanotubes on titanium for enhancing chondrocyte adhesion. In this manner, the results of the present in vitro study indicated that anodization might be a promising quick and inexpensive method to modify the surface of titanium-based implants to induce better chondrocyte adhesion for cartilage applications.

Surface engineered surgical tools and medical devices

Surface engineered surgical tools and medical devices / , Surface engineered surgical tools and medical devices / , کتابخانه دیجیتال جندی شاپور اهواز

Nanostructured polyurethane-poly-lactic-co-glycolic acid scaffolds increase bladder tissue regeneration: an in vivo study.

Although showing much promise for numerous tissue engineering applications, polyurethane and poly-lactic-co-glycolic acid (PLGA) have suffered from a lack of cytocompatibility, sometimes leading to poor tissue integration. Nanotechnology (or the use of materials with surface features or constituent dimensions less than 100 nm in at least one direction) has started to transform currently implanted materials (such as polyurethane and PLGA) to promote tissue regeneration. This is because nanostructured surface features can be used to change medical device surface energy to alter initial protein adsorption events important for promoting tissue-forming cell functions. Thus, due to their altered surface energetics, the objective of the present in vivo study was to create nanoscale surface features on a new polyurethane and PLGA composite scaffold (by soaking the polyurethane side and PLGA side in HNO3 and NaOH, respectively) and determine bladder tissue regeneration using a minipig model. The novel nanostructured scaffolds were further functionalized with IKVAV and YIGSR peptides to improve cellular responses. Results provided the first evidence of increased in vivo bladder tissue regeneration when using a composite of nanostructured polyurethane and PLGA compared with control ileal segments. Due to additional surgery, extended potentially problematic healing times, metabolic complications, donor site morbidity, and sometimes limited availability, ileal segment repair of a bladder defect is not optimal and, thus, a synthetic analog is highly desirable. In summary, this study indicates significant promise for the use of nanostructured polyurethane and PLGA composites to increase bladder tissue repair for a wide range of regenerative medicine applications, such as regenerating bladder tissue after removal of cancerous tissue, disease, or other trauma.

Decreased bacteria density on nanostructured polyurethane

As is well known, medical device infections are a growing clinical problem with no clear solution due to previous failed attempts of using antibiotics to decrease bacteria functions for which bacteria quickly develop a resistance toward. Because of their altered surface energetics, the objective of the present in vitro study was to create nanoscale surface features on polyurethane (PU) by soaking PU films in HNO3 and to determine bacteria (specifically, S. epidermidis, E. coli, and P. mirabilis) colony forming units after 1 h. Such bacteria frequently infect numerous medical devices. Results provided the first evidence that without using antibiotics, S. epidermidis density decreased by 5 and 13 times, E. coli density decreased by 6 and 20 times, and P. mirabilis density decreased by 8 and 35 times compared to conventional PU and a tissue engineering control small intestine submucosa (SIS), respectively. Material characterization studies revealed significantly greater nanoscale roughness and hydrophobicity for the HNO3-treated nanostructured PU compared to conventional PU (albeit, still hydrophilic) which may provide a rationale for the observed decreased bacteria responses. In addition, significantly greater amounts of fibronectin adsorption from serum were measured on nanorough compared conventional PU which may explain the decreased bacteria growth. In summary, this study provides significant promise for the use of nanostructured PU to decrease bacteria functions without the use of antibiotics, clearly addressing the wide spread problem of increased medical device infections observed today.

Developing Biosensors for Monitoring Orthopedic Tissue Growth

The objective of this present study was to create a biosensor which can monitor in situ orthopedic tissue growth juxtaposed to a newly implanted orthopedic material. This biosensor has unique properties including the ability to sense, detect, and control bone regrowth. Such a biosensor is useful to not only regenerate tissue necessary for orthopedic implant success but it also aids in informing an orthopedic surgeon if sufficient new bone growth occurred. If the sensor determines that insufficient new bone growth occurred, the sensor can also act in an intelligent manner to release bone growth factors to increase bone formation. The primary biomaterial in this biosensor is anodized titanium, developed by chemical etching, and passivation treatments. Carbon nanotubes (CNTs), in terms of their electrical and mechanical properties, are imperative considerations when designing such biosensors since they will be used to apply and measure conductivity changes as new bone grows next to the implant. For this, parallel multiwall CNTs were grown from the pores of the anodized titanium by the chemical vapor deposition process. Lastly, this sensor is composed of a conductive, biodegradable, polymer layer that degrades when bone grows and, consequently, undergoes a change in conductivity that can be measured by the CNTs grown out of the anodized titanium. This conductive, biodegradable polymer consists of polypyrrole (which is conductive) and polylactic-co-glycolic acid (which is biodegradable). Preliminary in vitro results suggest that osteoblast functions (adhesion and proliferation) on such a biosensor is not significantly compromised when compared to currently-used titanium, yet, retains the ability to potentially measure new bone growth juxtaposed to an implant. In addition, although not tested here, it is anticipated that bone growth could be enhanced on these biosensors electrically.

Carbon nanotubes-titanium electrode for detecting calcium deposition by osteoblasts

The objective of this in vitro present study was to develop an electrode which can detect calcium deposition by osteoblasts. The primary biomaterial for this electrode is anodized Ti, developed by chemical etching and passivation treatments. Carbon nanotubes (CNTs), because of their enhancement in electron transfer reaction, are essential to consider when designing the electrodes. For this, parallel multiwall CNTs were grown from the pores of the anodized Ti by a chemical vapor deposition process. Preliminary in vitro results suggest that osteoblast functions (specifically alkaline phosphatase activity and calcium deposition) on CNTs grown on anodized Ti are significantly enhanced when compared to anodized Ti and currently-used Ti; thus, it is anticipated that bone growth could be enhanced on these biomaterial electrodes.