Choice Of Biomaterials Research Articles

E-Cadherin – Fc Chimeric Protein-Based Biomaterial: Breaking the Barriers in Stem Cell Technology and Regenerative Medicine

Chimeric proteins have been used for years for various purposes ranging from biomaterials to candidate drug molecules, and from bench to bulk. Regenerative medicine needs various kinds of proteins for providing essential factors for maintaining starting cells, like induced pluripotent stem cells (iPSC), and renewal, proliferation, targeted differentiation of these cells, and as extracellular matrix for the experimental cells. However, there are several challenges associated with making functional chimeric proteins for effective application as biomaterial in this field. Fc-chimeric protein technology could be an effective solution to overcome many of them. These tailored proteins are recently becoming superior choice of biomaterials in stem cell technology and regenerative medicine due to their specific advantageous biophysical and biochemical properties over other chimeric forms of same proteins. Recent advances in recombinant protein-related science and technology also expedited the popularity of this kind of engineered protein. Over the last decade our lab has been pioneering this field, and we and others have been successfully applied Fc-chimeric proteins to overcome many critical issues in stem cell technologies targeting regenerative medicine and tissue engineering. Fc-chimeric protein-based biomaterials, specifically, E-cad-Fc have been preferentially applied for coating of cell culture plates for establishing xenogeneic-agent free monolayer stem cell culture and their maintenance, enhanced directed differentiation of stem cells to specific lineages, and non-enzymatic on-site one-step purification of target cells. Here the technology, recent discoveries, and future direction related with the E-cad-Fc-chimeric protein in connection with regenerative medicine are described.

Biological therapy of strontium-substituted bioglass for soft tissue wound-healing: Responses to oxidative stress in ovariectomised rats

New synthetic biomaterials are constantly being developed for wound repair and regeneration. Bioactive glasses (BG) containing strontium have shown successful applications in tissue engineering account of their biocompatibility and the positive biological effects after implantation. This study aimed to assess whether BG-Sr was accepted by the host tissue and to characterize oxidative stress biomarker and antioxidant enzyme profiles during muscle and skin healing. Wistar rats were divided into five groups (six animals per group): the group (I) was used as negative control (T), after ovariectomy, groups II, III, IV and V were used respectively as positive control (OVX), implanted tissue with BG (OVX-BG), BG-Sr (OVX-BG-Sr) and presented empty defects (OVX-NI). Soft tissues surrounding biomaterials were used to estimate superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) concentration. Our results show that 60 days after operation, treatment of rats with BG-Sr significantly increased MDA concentration and caused an increase of SOD, CAT and GPx activities in both skin and muscular tissues. BG-Sr revealed maturation of myotubes followed a normal appearance of muscle regenerated with high density and mature capillary vessels. High wound recovery with complete re-epithelialization and regeneration of skin was observed. The results demonstrate that the protective action against reactive oxygen species (ROS) was clearly observed in soft tissue surrounding BG-Sr. Moreover, the potential use of BG-Sr rapidly restores the wound skin and muscle structural and functional properties. The BG advantages such as ion release might make BG-Sr an effective biomaterial choice for antioxidative activity.

Choice of biomaterials—Do soft occlusal splints influence jaw-muscle activity during sleep? A preliminary report

AimThe choice of biomaterials for occlusal splints may significantly influence biological outcome. In dentistry, hard acrylic occlusal splints (OS) have been shown to have a temporary and inhibitory effect on jaw-muscle activity, such as tooth clenching and grinding during sleep, i.e., sleep bruxism (SB). Traditionally, this inhibitory effect has been explained by changes in the intraoral condition rather than the specific effects of changes in occlusion. The aim of this preliminary study was to investigate the effect of another type of occlusal surface, such as a soft-material OS in addition to a hard-type OS in terms of changes in jaw-muscle activity during sleep. Materials and methodsSeven healthy subjects (mean±SD, six men and one woman: 28.9±2.7 year old), participated in this study. A soft-material OS (ethylene vinyl acetate copolymer) was fabricated for each subject and the subjects used the OS for five continuous nights. The EMG activity during sleep was compared to baseline (no OS). Furthermore, the EMG activity during the use of a hard-type OS (Michigan-type OS, acrylic resin), and hard-type OS combined with contingent electrical stimulation (CES) was compared to baseline values. Each session was separated by at least two weeks (washout). Jaw-muscle activity during sleep was recorded with single-channel ambulatory devices (GrindCare, MedoTech, Herlev, Denmark) in all sessions for five nights. ResultsJaw-muscle activity during sleep was 46.6±29.8 EMG events/hour at baseline and significantly decreased during the hard-type OS (17.4±10.5, P=0.007) and the hard-type OS+CES (10.8±7.1, P=0.002), but not soft-material OS (36.3±24.5, P=0.055). Interestingly, the soft-material OS (coefficient of variance=98.6±35.3%) was associated with greater night-to-night variations than baseline (39.0±11.8%) and the hard-type OS+CES (53.3±13.7%, P<0.013). ConclusionThe present pilot study in small sample showed that a soft-material occlusal splint does not seem to inhibit jaw-muscle activity during sleep. Within the limitation of the study, it appears that the choice of biomaterials for occlusal splints may have a significant impact on the neurobiological regulation of jaw-muscle activity during sleep.

Esthetic and Functional Rehabilitation of a Bilateral Cleft Palate Patient with Fixed Prosthodontic Therapy

Patients with bilateral cleft lip and palate present with multiple challenges to the prosthodontist. Some of them include mobility of the premaxillary segment, multiple missing and malposed anterior teeth, unfavorable soft tissues, and a tense maxillary lip. This clinical report describes the fixed prosthodontic management of a bilateral cleft lip and palate patient with a surgically corrected lip and a mobile premaxillary segment. The patient presented with an 11-unit metal-ceramic fixed partial denture made of a base metal alloy that was made 25 years ago. He had multiple porcelain fractures over the years that compromised his esthetics and function. Prosthodontic therapy involved sectioning the old prosthesis, followed by careful treatment planning and fabrication of a new fixed dental prosthesis with improved design and superior materials. At a 3-year follow-up, the fixed dental prosthesis remained intact and functional, and no further complications were noted. A discussion of approaches to treatment planning, biomechanical principles involved, and choice of biomaterials in designing a fixed prosthesis for such patients is presented. As cleft palate patients require life-long prosthodontic follow-up and maintenance, revisional treatments should incorporate superior materials and methods to minimize future complications.

Strontium-substituted bioactive glass coatings for bone tissue engineering

control 0%Sr 10%Sr 50%Sr % Strontium Substitution N or m al is ed M TT A ct iv ity Day1 Day 7 Day14    Strontiumsubstituted Bioactive Glass Coatings for Bone Tissue Engineering Nasrin Lotfibakhshaiesh , Eileen Gentleman, Robert G Hill, Molly M Stevens Corresponding Author: m.stevens@imperial.ac.uk Department of Materials & Institute of Biomedical Engineering, Imperial College, London, UK Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, UK Introduction Metallic prosthetic implants are widely used to treat joint and skeletal injuries. However, some implants can fail because the metal alloys used do not bond with bone. Bioactive glass (BG) coatings may offer a solution to this problem as they form a strong bond with living tissue and have the added benefit that their dissolution ions stimulate cell activity. Strontium ranelate, a drug used to treat and prevent osteoporosis works via the action of Sr ions which stimulate the formation of new bone and prevent osteoclast-mediated resorbtion. Sr can be substituted for calcium in BGs creating a material that may combine the bone remodelling benefits of Sr ions with the well-established bone stimulatory action of bioactive glass. The aim of this study is to develop Sr containing BG coatings on metallic surfaces to bond to an implant as an effective biomaterial choice for a range of bone regeneration therapies. Materials and Methods Bioactive glasses in the system: SiO2-MgONa2O-K2O-ZnO-P2O5-CaO with 0, 10, and 50 of the Ca being replaced by Sr were prepared by a melt-quench route. A degradation study was carried out on <38μm glass powders in simulated body fluids. Silicon [Si], Phosphorus [P], Calcium [Ca] and Sr were checked at different time periods: 10, 30, 60, 120, 240 and 480 min. Produced glasses were combined with RPMI media on a roller for 4 hours at 37°C and then passed through a 0.2 μm filter. This media was then supplemented with 10% foetal bovine serum, 2mM L-glutamine and 1% penicillin/ streptomycin. The human osteosarcoma cell line, Saos-2, was seeded (30,000 cells/cm) in Sr substituted medium and cultured for up to 28 days. On days 1, 7 and 14 post-planting cell metabolic activity was measured using the tetrazole MTT. BGs were coated on to the surface of Ti6AL4V coupons and were sterilised under UV light both side. 10,000 Saos-2 cells/cm2 were seeded on BG coatings and viability was assessed after 1, 7 and 14 days with a Live/Dead stain. Results Glass dissolution leads to a rise of all the ion concentrations in solution. When [Si] hits the solubility limit, [P] declines. At this point a silica gel layer will start to form on the surface and this might be expected to promote nucleation of HCA consuming the P.[Ca] follows the [P] decrease in low Ca content glasses but decreases then rises in high Ca content glasses. Finally, Sr increases the overall concentration of ions in solution. MTT activity (Fig.1) increased in all samples with time in culture until 14 days. Saos2 cultured treated with Sr-substituted BGs had higher MTT activities than controls. Live/Dead staining showed that cells were alive on all coating materials.

Influence of Crimping Process Parameters on Vascular Prostheses Mechanical Performances

Textile prostheses made of polyethylene terephthalate fibers are commonly used to cure cardiovascular pathologies by replacing diseased arteries. Any failure of vascular surgery is not only expensive, but also unacceptable. Biocompatibility, biofunctionality and biodurability must be taken into consideration especially with the increasing life expectancy of the population. An outstanding development of vascular prostheses might be achieved by a better choice of biomaterials and an optimization of manufacturing processes, especially the crimping technique. Crimping is an "accordion"-pleat deformation, which gives the graft a radial resistance and a longitudinal compliance. It also improves the resistance of the prosthesis to kinking and external compression. The aim of the present study is to compare the effect of three thermofixing techniques used for vascular prosthesis crimping. This will help to find the crimping process that leads to the lowest reduction of the mechanical performances of the material. We have demonstrated that the heat-setting in saturated vapor introduces the best mechanical behavior of crimped woven tubes in comparison to heat-settings with dry heat and boiling water.

Zirconia Toughened Alumina (ZTA) Powders: Ultrastructural and Histological Analysis

Ceramic materials, as Alumina and Zirconia, has made an improvement in the choice of new biomaterials for the load bearing application in dental and orthopaedic implants. These materials has shown mechanical resistance to high stress related to weight bearing and low debris in time. For this reason they are indicated on young patients implant, with high demanding activities and long life expectance. In literature however the risk of chronic inflammation due to chronic wear debris release and the possibility of carcinogenesis, is still to be definitively investigated. Another point to investigate is the acute reaction of the tissue in case of acute release of powders of these materials. The aim of this study was to investigate the possible local and systemic acute effects of ceramic precursors in form of powders of different size when released into articular joint. Powders of ZTA were implanted in the knee joint of twenty-four New Zealand white adult rabbits, that were sacrificed at 1,3,6, and 12 months. Radiographic, histological and immunoistochemestry analysis were conducted on periprosthetic tissue and peripheral organs, to verifying local host response and systemic toxic effects.

Incorporation of biomaterials in multicellular aggregates modulates pluripotent stem cell differentiation

Biomaterials are increasingly being used to engineer the biochemical and biophysical properties of the extracellular stem cell microenvironment in order to tailor niche characteristics and direct cell phenotype. To date, stem cell–biomaterial interactions have largely been studied by introducing stem cells into artificial environments, such as 2D cell culture on biomaterial surfaces, encapsulation of cell suspensions within hydrogel materials, or cell seeding on 3D polymeric scaffolds. In this study, microparticles fabricated from different materials, such as agarose, PLGA and gelatin, were stably integrated, in a dose-dependent manner, within aggregates of pluripotent stem cells (PSCs) prior to differentiation as a means to directly examine stem cell–biomaterial interactions in 3D. Interestingly, the presence of the materials within the stem cell aggregates differentially modulated the gene and protein expression patterns of several differentiation markers without adversely affecting cell viability. Microparticle incorporation within 3D stem cell aggregates can control the spatial presentation of extracellular environmental cues (i.e. soluble factors, extracellular matrix and intercellular adhesion molecules) as a means to direct the differentiation of stem cells for tissue engineering and regenerative medicine applications. In addition, these results suggest that the physical presence of microparticles within stem cell aggregates does not compromise PSC differentiation, but in fact the choice of biomaterials can impact the propensity of stem cells to adopt particular differentiated cell phenotypes.

The effects of strontium-substituted bioactive glasses on osteoblasts and osteoclasts in vitro

Bioactive glasses (BG) which contain strontium have the potential to combine the known bone regenerative properties of BG with the anabolic and anti-catabolic effects of strontium cations. Here we created a BG series (SiO 2–P 2O 5–Na 2O–CaO) in which 0–100% of the calcium was substituted by strontium and tested their effects on osteoblasts and osteoclasts in vitro. We show that ions released from strontium-substituted BG enhance metabolic activity in osteoblasts. They also inhibit osteoclast activity by both reducing tartrate resistant acid phosphatase activity and inhibiting resorption of calcium phosphate films in a dose-dependent manner. Additionally, osteoblasts cultured in contact with BG show increased proliferation and alkaline phosphatase activity with increasing strontium substitution, while osteoclasts adopt typical resorption morphologies. These results suggest that similarly to the osteoporosis drug strontium ranelate, strontium-substituted BG may promote an anabolic effect on osteoblasts and an anti-catabolic effect on osteoclasts. These effects, when combined with the advantages of BG such as controlled ion release and delivery versatility, may make strontium-substituted BG an effective biomaterial choice for a range of bone regeneration therapies.

Biomaterials in Craniofacial Surgery

The increasing variety of biomaterials available to the craniofacial surgeon today, with advantages of "off-the-shelf availability" and lack of donor-site morbidity, provides a formidable armamentarium for applications in reconstruction and augmentation. Although biomaterials are invaluable alternatives to autogenous bone graft, there is lack of uniformity in clinical application. In this article, we review our experience with the use of hydroxyapatite derivatives in animal studies and subsequently discuss our experience with the use of 3 classes of biomaterials (cement pastes, osteoactive biomaterials, and prefabricated polymers) for craniofacial reconstruction. We subsequently offer guidelines to dictate the choice of biomaterials for different applications, based on the site of reconstruction (onlay versus inlay reconstruction) and skeletal maturity.

Adhesion contact dynamics of primary hepatocytes on poly(ethylene terephthalate) surface

The design of bioartificial liver assist device requires an effective attachment of primary hepatocytes on polymeric biomaterials. A better understanding of this cell-surface interaction would aid the optimal choice of biomaterials. In this study, the adhesion contact dynamics of primary hepatocytes on poly(ethylene terephthalate) (PET) surface with grafted poly(acrylic acid) (PAA) and coated collagen is probed with confocal reflectance interference contrast microscopy (C-RICM) in conjunction with phase contrast microscopy. An increase of acrylic acid density from 0 to 12 nmole/cm 2 raises both the root-mean-square surface roughness and amount of adsorbed collagen of PET surface. C-RICM demonstrates that hepatocytes form tight adhesion contacts upon seeding on both plain PET and PAA-grafted PET (both with collagen coating) despite the insignificant two-dimensional cell spreading. At two hours after cell seeding, the normalized contact area and adhesion energy of hepatocytes on 12 nmole/cm 2 PAA-grafted-PET (with collagen coating) is 27% and 114% higher, respectively, than that on collagen coated plain PET. Interestingly, the growth kinetics of adhesion patch for hepatocyte on PAA-grafted PET with collagen coating is best fitted by R∝ t 0.5 and is significantly different from that on collagen coated plain PET, which is best fitted by R∝ t 0.25. Overall, this study demonstrates the modulation of biophysical response of adherent hepatocytes through the control of the biomaterial surface properties.

Adhesion contact dynamics of primary hepatocytes on poly(ethylene terephthalate) surface

The design of bioartificial liver assist device requires an effective attachment of primary hepatocytes on polymeric biomaterials. A better understanding of this cell-surface interaction would aid the optimal choice of biomaterials. In this study, the adhesion contact dynamics of primary hepatocytes on poly(ethylene terephthalate) (PET) surface with grafted poly(acrylic acid) (PAA) and coated collagen is probed with confocal reflectance interference contrast microscopy (C-RICM) in conjunction with phase contrast microscopy. An increase of acrylic acid density from 0 to 12 nmole/cm2 raises both the root-mean-square surface roughness and amount of adsorbed collagen of PET surface. C-RICM demonstrates that hepatocytes form tight adhesion contacts upon seeding on both plain PET and PAA-grafted PET (both with collagen coating) despite the insignificant two-dimensional cell spreading. At two hours after cell seeding, the normalized contact area and adhesion energy of hepatocytes on 12 nmole/cm2 PAA-grafted-PET (with collagen coating) is 27% and 114% higher, respectively, than that on collagen coated plain PET. Interestingly, the growth kinetics of adhesion patch for hepatocyte on PAA-grafted PET with collagen coating is best fitted by R∝t0.5 and is significantly different from that on collagen coated plain PET, which is best fitted by R∝t0.25. Overall, this study demonstrates the modulation of biophysical response of adherent hepatocytes through the control of the biomaterial surface properties.

Biomechanical considerations on shoulder joint prosthesis implantation

The biomechanical goals of prosthetic reconstruction of the shoulder are to restore the normal anatomy and range of motion, and to recreate the normal soft tissue balance of the static and dynamic stabilizers of the glenohumeral joint. An unconstrained prosthesis design best reproduces the physiological articulation and original anatomy of the shoulder. Humeral head components have been recently developed, which are adaptable to the variable anatomy of the proximal humerus (third generation design). A precise reconstruction of the three dimensional structure of the proximal humerus may lead to an improved functional outcome. However, there is still a lack of biomechanical data to support this concept. The optimal design of the glenoid component remains a challenge for future research. Specific issues including the choice of biomaterials, the optimum shape, radius of curvature, surface area of the articulation, component height and stem design remain under investigation. Although the prosthetic design represents an important factor in the success of glenohumeral arthroplasty, the surgical reconstruction of the soft tissues to recreate the normal soft tissue balance as well as postoperative rehabilitation determine the functional outcome.

Selection of Biomaterials for Middle and Inner Ear Implants

In the selection of biomaterials for middle ear applications of implantable devices, certainly the site of implantation and the mass of the implant will dictate the choice of biomaterials. Hermetic sealing of an implant is best achieved by the use of metals, not polymers. Osteocompatibility of an ossicular implant can be enhanced by the incorporation of calcium phosphates such as hydroxyapatite coatings. Finally, osseointegration or osseofixation is neither necessary nor desirable for ossicular implants, because (1) they may need to be removed or replaced in the future and (2) their solid fixation to an ossicle is not necessary for the vibratory function of hearing amplification.