Journal of Functional Biomaterials — Open Access Journal

Pathologic calcification leads to structural deterioration of implant materials via stiffening, stress cracking, and other structural disintegration mechanisms, and the effect can be critical for implants intended for long-term or permanent implantation. This study demonstrates the potential of using specific metal ions (MI)s for inhibiting pathological calcification in polyurethane (PU) implants. The hypothesis of using MIs as anti-calcification agents was based on the natural calcium-antagonist role of Mg²⁺ ions in human body, and the anti-calcification effect of Fe³⁺ ions in bio-prosthetic heart valves has previously been confirmed. In vitro calcification results indicated that a protective covering mesh of MI-doped PU can prevent calcification by preventing hydroxyapatite crystal growth. However, microstructure and mechanical characterisation revealed oxidative degradation effects from Fe³⁺ ions on the mechanical properties of the PU matrix. Therefore, from both a mechanical and anti-calcification effects point of view, Mg²⁺ ions are more promising candidates than Fe³⁺ ions. The in vitro MI release experiments demonstrated that PU microphase separation and the structural design of PU-MI matrices were important determinants of release kinetics. Increased phase separation in doped PU assisted in consistent long-term release of dissolved MIs from both hard and soft segments of the PU. The use of a composite-sandwich mesh design prevented an initial burst release which improved the late (>20 days) release rate of MIs from the matrix. Full article

The objective of this study was to evaluate microwave heating enhancements offered by iron/iron oxide nanoparticles dispersed within tissue-mimicking media for improving efficacy of microwave thermal therapy. The following dopamine-coated magnetic nanoparticles (MNPs) were considered: 10 and 20 nm diameter spherical core/shell Fe/Fe₃O₄, 20 nm edge-length cubic Fe₃O₄, and 45 nm edge-length/10 nm height hexagonal Fe₃O₄. Microwave heating enhancements were experimentally measured with MNPs dissolved in an agar phantom, placed within a rectangular waveguide. Effects of MNP concentration (2.5–20 mg/mL) and microwave frequency (2.0, 2.45 and 2.6 GHz) were evaluated. Further tests with 10 and 20 nm diameter spherical MNPs dispersed within a two-compartment tissue-mimicking phantom were performed with an interstitial dipole antenna radiating 15 W power at 2.45 GHz. Microwave heating of 5 mg/mL MNP-agar phantom mixtures with 10 and 20 nm spherical, and hexagonal MNPs in a waveguide yielded heating rates of 0.78 ± 0.02 °C/s, 0.72 ± 0.01 °C/s and 0.51 ± 0.03 °C/s, respectively, compared to 0.5 ± 0.1 °C/s for control. Greater heating enhancements were observed at 2.0 GHz compared to 2.45 and 2.6 GHz. Heating experiments in two-compartment phantoms with an interstitial dipole antenna demonstrated potential for extending the radial extent of therapeutic heating with 10 and 20 nm diameter spherical MNPs, compared to homogeneous phantoms (i.e., without MNPs). Of the MNPs considered in this study, spherical Fe/Fe₃O₄ nanoparticles offer the greatest heating enhancement when exposed to microwave radiation. These nanoparticles show strong potential for enhancing the rate of heating and radial extent of heating during microwave hyperthermia and ablation procedures. Full article

Titanium and titanium alloy materials are commonly used in joint replacements, due to the high strength of the materials. Pathogenic microorganisms can easily adhere to the surface of the metal implant, leading to an increased potential for implant failure. The surface of a titanium-aluminum-vanadium (Ti-6Al-4V) metal oxide implant material was functionalized to deliver an small antibacterial molecule, nitric oxide. S-nitroso-penicillamine, a S-nitrosothiol nitric oxide donor, was covalently immobilized on the metal oxide surface using self-assembled monolayers. Infrared spectroscopy was used to confirm the attachment of the S-nitrosothiol donor to the Ti-Al-4V surface. Attachment of S-nitroso-penicillamine resulted in a nitric oxide (NO) release of 89.6 ± 4.8 nmol/cm² under physiological conditions. This low concentration of nitric oxide reduced Escherichia coli and Staphylococcus epidermidis growth by 41.5 ± 1.2% and 25.3 ± 0.6%, respectively. Combining the S-nitrosothiol releasing Ti-6Al-4V with tetracycline, a commonly-prescribed antibiotic, increased the effectiveness of the antibiotic by 35.4 ± 1.3%, which allows for lower doses of antibiotics to be used. A synergistic effect of ampicillin with S-nitroso-penicillamine-modified Ti-6Al-4V against S. epidermidis was not observed. The functionalized Ti-6Al-4V surface was not cytotoxic to mouse fibroblasts. Full article

Laser ablation (LA) is gaining acceptance for the treatment of tumors as an alternative to surgical resection. This paper reviews the use of lasers for ablative and surgical applications. Also reviewed are solutions aimed at improving LA outcomes: hyperthermal treatment planning tools and thermometric techniques during LA, used to guide the surgeon in the choice and adjustment of the optimal laser settings, and the potential use of nanoparticles to allow biologic selectivity of ablative treatments. Promising technical solutions and a better knowledge of laser-tissue interaction should allow LA to be used in a safe and effective manner as a cancer treatment. Full article

The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (poly(l-lactic acid) and poly(ε-caprolactone), PLLA and PCL, respectively) as well as collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter (nucleus/cytoplasm area ratio) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC₅₀) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy. Full article

Implant surface topography is a key factor in achieving osseointegration. l-Threonine can be chemically and stably bonded to titanium surfaces by phosphorylation. This study investigated the degree of in vivo osseointegration of an implant with a novel o-phospho-l-threonine (p-Thr)-binding surface. MC3T3-E1 cells were seeded on the p-Thr binding surface and machined surface disks, and initial cell attachment was evaluated. p-Thr-binding and machined surface implants were tested in vivo by implantation into the femurs of three male New Zealand white rabbits, and the osseointegration was assessed by measurement of removal torque (RT) and bone-implant contact (BIC) ratio. Initial cell attachment was greater for the p-Thr-binding than for the machined surface implant group (P < 0.05). In addition, RT and BIC values were higher for the p-Thr-binding surface than for the machined surface (P < 0.05). These results indicate that our implant with a p-Thr-binding surface can achieve enhanced osseointegration. Full article

Rapid and complete soft tissue healing after tooth extraction minimizes surgical complications and facilitates subsequent implant placement. We used four treatment methods and assessed changes in soft tissue socket closure following tooth extraction in humans. The effects of platelet-rich fibrin-calcium sulfate hemihydrate (PRF-CSH), platelet-rich plasma-calcium sulfate hemihydrate (PRP-CSH), a resorbable collagen dressing (RCD), and no grafting material were compared in a randomized, controlled pilot study with a blinded parallel design (N = 23). Patients with a hopeless tooth scheduled for extraction were randomly assigned to one of the four treatment groups. Socket measurements were obtained immediately after extraction and treatment, as well as after 21 days. There was a significant decrease in the total epithelialized external surface area of the extraction sockets in each group at all time points. However, there were no significant differences in soft tissue closure (p > 0.05) at any time point and PRF-CSH or PRP-CSH did not provide any additional benefit to enhance the soft tissue closure of extraction sockets compared with either RCD or sites without graft. Full article

Constipation is a gastrointestinal motility disorder that represents a major health problem in Japan. Approximately 26% of young Japanese adult women are reported to have this complaint. We report on the health effects of daily intake of Sujiaonori algal biomaterial (SBM) on constipation on 12 Japanese adult women. Data are from a four-week dietary intervention study on the health effects of daily Sujiaonori supplementation on cardiovascular, skin, and gastrointestinal health in which 32 adult Japanese volunteers (age range: 20–54 years) participated. They underwent clinical and laboratory investigations, and completed two study questionnaires (the brief diet history questionnaire (BDHQ) and the current health questionnaire) before and after dietary intervention. Of the 12 women volunteers with functional constipation, there were six SBM-supplemented subjects who received 3 g of Sujiaonori powder twice daily during meal, whereas the six others (controls) were from the group of those who took 3 g of a power made of 70% corn starch and 30% Japanese spinach mixture. The analysis of data on daily nutrient intake showed no significant dietary changes for nutrients (minerals, proteins, fiber, fat) and calorie intake (except alcohol intake that was reduced) in both groups. In SBM group, a significant reduction of the proportion of women with constipation was observed (p < 0.001), whereas no significant change was noted within the control group (p > 0.05). When both groups were compared, SBM was more effective than the control product; 66.7% (4/6) of SBM-supplemented women had their constipation relieved, whereas only one control (16.7%) controls benefited from dietary intervention (p < 0.001). In addition, no adverse effect was reported in the SBM group, whereas two controls reported nausea at post-survey. These results suggest that Sujiaonori contains compounds that can improve gastrointestinal function and relieve constipation. Full article

We suggest a novel method that uses artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port-wine stains (i.e., capillary malformations presenting as red birthmarks) based on the results of animal experiments. As compared with human red blood cells, Hb-Vs have the same absorbance of 595 nm wavelength light and produce the same level of heat following dye laser irradiation. Small sized Hb-Vs (250 nm) distribute in the plasma phase in blood and tend to flow in the marginal zone of microvessels. Intravenous injections of Hb-Vs caused the dilatation of microvessels, and dye laser treatment with Hb-Vs destroyed the vessel wall effectively. Following the intravenous injection of Hb-Vs, the microvessels contained more Hb that absorbed laser photons and produced heat. This extra Hb tended to flow near the endothelial cells, which were the target of the laser treatment. These attributes of Hb-Vs will potentially contribute to enhancing the efficacy of dye laser treatment for port-wine stains. Hemoglobin is a type of porphyrin. Thus, our proposed treatment may have aspects of photodynamic therapy using porphyrin that leads to a cytotoxicity effect by active oxygen. Full article

Within the Ear, Nose, and Throat (ENT) medical space, a relatively small fraction of patients follow through with elective surgeries to fix ailments such as a deviated septum or occluded sinus passage. Patient understanding of their diagnosis and treatment plan is integral to compliance, which ultimately yields improved medical outcomes and better quality of life. Here we report the usage of advanced, polyjet 3D printing methods to develop a multimaterial replica of human nasal sinus anatomy, derived from clinical X-ray computed tomography (CT) data, to be used as an educational aid during physician consultation. The final patient education model was developed over several iterations to optimize material properties, anatomical accuracy and overall display. A two-arm, single-center, randomized, prospective study was then performed in which 50 ENT surgical candidates (and an associated control group, n = 50) were given an explanation of their anatomy, disease state, and treatment options using the education model as an aid. Statistically significant improvements in patient ratings of their physician’s explanation of their treatment options (p = 0.020), self-rated anatomical understanding (p = 0.043), self-rated understanding of disease state (p = 0.016), and effectiveness of the visualization (p = 0.007) were noted from the population that viewed the 3D education model, indicating it is an effective tool which ENT surgeons may use to educate and interact with patients. Full article

Minimally invasive techniques to occlude flow within blood vessels, initially pioneered in the 1970s with autologous materials and subsequently advanced with increasingly sophisticated engineered biomaterials, are routinely performed for a variety of medical conditions. Contemporary interventional radiologists have at their disposal a wide armamentarium of occlusive agents to treat a range of disease processes through a small incision in the skin. In this review, we provide a historical perspective on endovascular embolization tools, summarize the current state-of-the-art, and highlight burgeoning technologies that promise to advance the field in the near future. Full article

Hemoglobin (Hb) is an ideal material for use in the development of an oxygen carrier in view of its innate biological properties. However, the vascular retention of free Hb is too short to permit a full therapeutic effect because Hb is rapidly cleared from the kidney via glomerular filtration or from the liver via the haptogloblin-CD 163 pathway when free Hb is administered in the blood circulation. Attempts have been made to develop alternate acellular and cellular types of Hb based oxygen carriers (HBOCs), in which Hb is processed via various routes in order to regulate its pharmacokinetic properties. These HBOCs have been demonstrated to have superior pharmacokinetic properties including a longer half-life than the Hb molecule in preclinical and clinical trials. The present review summarizes and compares the pharmacokinetic properties of acellular and cellular type HBOCs that have been developed through different approaches, such as polymerization, PEGylation, cross-linking, and encapsulation. Full article

Hemoglobin (Hb) is the most abundant protein in whole blood. This fact implies that the oxygen binding and releasing function of Hb is the most vital for sustaining life. All Hb is compartmentalized in red blood cells (RBCs) with corpuscular Hb concentration of about 35 g/dL, covered with a thin biomembrane. In spite of its abundance, Hb sometimes shows toxicity once it is leaked from RBCs. The shielding effect of the RBC membrane is physiologically important. Based on this structural importance, we have studied artificial red cells (Hb vesicles, HbV) as artificial oxygen carriers, which encapsulate a purified and concentrated Hb solution in phospholipid vesicles, mimicking the cellular structure of RBCs. Our academic research consortium has clarified the safety and efficacy of this HbV, aiming at clinical applications. Because of some superior characteristics to those of RBCs, HbV has the potential for use not only as a transfusion alternative but also for oxygen and carbon monoxide therapeutics, perfusate for transplant organs, and photosensitizer. In this review paper, such potential applications are summarized. Full article

Greige cotton is an intact plant fiber. The cuticle and primary cell wall near the outer surface of the cotton fiber contains pectin, peroxidases, superoxide dismutase (SOD), and trace metals, which are associated with hydrogen peroxide (H₂O₂) generation during cotton fiber development. Traditionally, the processing of cotton into gauze involves scouring and bleaching processes that remove the components in the cuticle and primary cell wall. The use of unbleached, greige cotton fibers in dressings, has been relatively unexplored. We have recently determined that greige cotton can generate low levels of H₂O₂ (5–50 micromolar). Because this may provide advantages for the use of greige cotton-based wound dressings, we have begun to examine this in more detail. Both brown and white cotton varieties were examined in this study. Brown cotton was found to have a relatively higher hydrogen peroxide generation and demonstrated different capacities for H₂O₂ generation, varying from 1 to 35 micromolar. The H₂O₂ generation capacities of white and brown nonwoven greige cottons were also examined at different process stages with varying chronology and source parameters, from field to nonwoven fiber. The primary cell wall of nonwoven brown cotton appeared very intact, as observed by transmission electron microscopy, and possessed higher pectin levels. The levels of pectin, SOD, and polyphenolics, correlated with H₂O₂ generation. Full article

An aneurysm is a balloon-like bulge in the wall of blood vessels, occurring in major arteries of the heart and brain. Biodegradable polymeric stent-assisted coiling is expected to be the ideal treatment of wide-neck complex aneurysms. This paper presents the development of methods to fabricate and optimally design biodegradable polymeric stents for aneurysms treatment. Firstly, a dispensing-based rapid prototyping (DBRP) system was developed to fabricate coil and zigzag structures of biodegradable polymeric stents. Then, compression testing was carried out to characterize the radial deformation of the stents fabricated with the coil or zigzag structure. The results illustrated the stent with a zigzag structure has a stronger radial stiffness than the one with a coil structure. On this basis, the stent with a zigzag structure was chosen for the development of a finite element model for simulating the real compression tests. The result showed the finite element model of biodegradable polymeric stents is acceptable within a range of radial deformation around 20%. Furthermore, the optimization of the zigzag structure was performed with ANSYS DesignXplorer, and the results indicated that the total deformation could be decreased by 35.7% by optimizing the structure parameters, which would represent a significant advance of the radial stiffness of biodegradable polymeric stents. Full article

Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers. Full article

Functional polymers currently represent a basic component of a large range of biological and biomedical applications including molecular release, tissue engineering, bio-sensing and medical imaging. Advancements in these fields are driven by the use of a wide set of biodegradable polymers with controlled physical and bio-interactive properties. In this context, microscopy techniques such as Atomic Force Microscopy (AFM) are emerging as fundamental tools to deeply investigate morphology and structural properties at micro and sub-micrometric scale, in order to evaluate the in time relationship between physicochemical properties of biomaterials and biological response. In particular, AFM is not only a mere tool for screening surface topography, but may offer a significant contribution to understand surface and interface properties, thus concurring to the optimization of biomaterials performance, processes, physical and chemical properties at the micro and nanoscale. This is possible by capitalizing the recent discoveries in nanotechnologies applied to soft matter such as atomic force spectroscopy to measure surface forces through force curves. By tip-sample local interactions, several information can be collected such as elasticity, viscoelasticity, surface charge densities and wettability. This paper overviews recent developments in AFM technology and imaging techniques by remarking differences in operational modes, the implementation of advanced tools and their current application in biomaterials science, in terms of characterization of polymeric devices in different forms (i.e., fibres, films or particles). Full article

Bioactive polymeric materials based on calcium phosphates have tremendous appeal for hard tissue repair because of their well-documented biocompatibility. Amorphous calcium phosphate (ACP)-based ones additionally protect against unwanted demineralization and actively support regeneration of hard tissue minerals. Our group has been investigating the structure/composition/property relationships of ACP polymeric composites for the last two decades. Here, we present ACP’s dispersion in a polymer matrix and the fine-tuning of the resin affects the physicochemical, mechanical, and biological properties of ACP polymeric composites. These studies illustrate how the filler/resin interface and monomer/polymer molecular structure affect the material’s critical properties, such as ion release and mechanical strength. We also present evidence of the remineralization efficacy of ACP composites when exposed to accelerated acidic challenges representative of oral environment conditions. The utility of ACP has recently been extended to include airbrushing as a platform technology for fabrication of nanofiber scaffolds. These studies, focused on assessing the feasibility of incorporating ACP into various polymer fibers, also included the release kinetics of bioactive calcium and phosphate ions from nanofibers and evaluate the biorelevance of the polymeric ACP fiber networks. We also discuss the potential for future integration of the existing ACP scaffolds into therapeutic delivery systems used in the precision medicine field. Full article

The anti-inflammatory and vasodilating effects of three selected dietary organic sulfur compounds (OSC), including diallyl disulfide (DADS), dimethyl disulfide (DMDS), and propyl disulfide (PDS), from Allium species were investigated. In the anti-inflammatory activity assay, the three OSC demonstrated significant inhibition of nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in LPS-induced RAW 264.7 cells. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in activated RAW 264.7 cells was inhibited by the three OSC, indicating that the three OSC prevented the LPS-induced inflammatory response in RAW 264.7 cells. For the vasodilative assay, the three OSC were ineffective in producing NO in SVEC4-10 cells, but they did enhance prostacyclin (PGI₂) production. The expression of COX-2 in SVEC4-10 cells was activated by DADS and DMDS. Pretreatment of SVEC4-10 cells with the three OSC decreased ROS generation in H₂O₂-induced SVEC4-10 cells. In addition, the three OSC significantly inhibited angiotensin-I converting enzyme (ACE). The up-regulation of PGI₂ production and COX-2 expression by DADS and DMDS and the reduction of ROS generation by DADS, DMDS, and PDS in SVEC4-10 cells contributed to the vasodilative effect of the three OSC. Collectively, these findings suggest that DADS, DMDS, and PDS are potential anti-inflammatory and vasodilative mediators. Full article

Wound healing continues to be a major burden to patients, though research in the field has expanded significantly. Due to an aging population and increasing comorbid conditions, the cost of chronic wounds is expected to increase for patients and the U.S. healthcare system alike. With this knowledge, the number of engineered products to facilitate wound healing has also increased dramatically, with some already in clinical use. In this review, the major biomaterials used to facilitate skin wound healing will be examined, with particular attention allocated to the science behind their development. Experimental therapies will also be evaluated. Full article