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A novel polyolefin called poly(styrene-block-isobutylene-block-styrene) (“SIBS”) originated from Joseph P. Kennedy's laboratory at the University of Akron (Akron, Ohio, United States) and was developed as a biomaterial for long-term implant applications by the author. SIBS has no cleavable groups on its backbone or sidechains, is comprised predominantly of alternating secondary and quaternary carbons on its backbone, which prevents embrittlement and cracking under flexion, and undergoes multiple purification steps which renders it extremely biocompatible and well-suited for long-term applications in the eye. This article explores two ophthalmic devices; 1) the PRESERFLO® MicroShunt (Santen Pharmaceutical Co. Ltd., Osaka, Japan) made from SIBS that lowers intraocular pressure to thwart progression of vision loss from glaucoma, and 2) a novel intraocular lens (IOL) made from crosslinked polyisobutylene, which is under-development by Xi'an Eyedeal Medical Technology Co., Ltd. (Xi'an, China) that does not glisten nor cloud over time, as do most conventional IOLs., Highlights • A novel class of ultra-biostable polyisobutylene-based biomaterials for long-term implant applications. • A novel class of polyisobutylene-based biomaterials that is not bioactive and elicits minimal foreign body reaction. • A device called the PRESERFLO® MicroShunt to treat glaucoma made from poly(styrene-block-isobutylene-block-styrene) (SIBS). • A novel crosslinked polyisobutylene material for intraocular lens applications that eliminates glistenings and halos.

PURPOSE To assess the safety and effectiveness of the PRESERFLO® MicroShunt (formerly InnFocus MicroShunt) in patients with primary open-angle glaucoma (POAG). DESIGN The MicroShunt, a controlled ab externo glaucoma filtration surgery device, was investigated in a 2-year, multicenter, single-arm study. PARTICIPANTS Eligible patients were aged 18-85 years with POAG inadequately controlled on maximal tolerated medical therapy with intraocular pressure (IOP) ≥18 and ≤35 mmHg or when glaucoma progression warranted surgery. METHODS The MicroShunt was implanted as a stand-alone procedure with adjunctive use of topical mitomycin C (MMC; 0.2-0.4 mg/ml) for 2-3 minutes. MAIN OUTCOME MEASURES The primary effectiveness outcome was IOP reduction and success (not requiring reoperation or pressure failures [IOP > 21 mmHg and < 20% reduction in IOP]) at year 1. Additional end points at year 2 included IOP reduction, success, glaucoma medications, adverse events (AEs), and reoperations. Results are reported in the overall population and subgroups of patients receiving 0.2 or 0.4 mg/ml MMC. RESULTS In 81 patients, mean (± standard deviation [SD]) IOP decreased from 21.7 ± 3.4 mmHg at baseline to 14.5 ± 4.6 mmHg at year 1 and 14.1 ± 3.2 mmHg at year 2 (P < 0.0001). Overall success (with and without supplemental glaucoma medication use) at year 1 was 74.1%. Mean (± SD) number of medications decreased from 2.1 ± 1.3 at baseline to 0.5 ± 0.9 at year 2 (P < 0.0001), and 73.8% of patients were medication free. Most common nonserious AEs were increased IOP requiring medication or selective laser trabeculoplasty (25.9%) and mild-to-moderate keratitis (11.1%). There were 6 (7.4%) reoperations and 5 (6.2%) needlings by year 2. In an analysis (post hoc) according to MMC concentration, overall success was 78.1% (0.2 mg/ml) and 74.4% (0.4 mg/ml; P = 0.710). In the 0.2 and 0.4 mg/ml MMC groups, 51.9% and 90.3% of patients were medication free, respectively (P = 0.001). There was a trend toward lower IOP and higher medication reduction in the 0.4 mg/ml MMC subgroup. CONCLUSIONS In this study, mean IOP and glaucoma medication reductions were significant and sustained over 2 years postsurgery. No long-term, sight-threatening AEs were reported. Further studies may confirm potential risk/benefits of higher MMC concentration.

Purpose of review Mitomycin C (MMC) is an alkylating agent with extraordinary ability to crosslink DNA, preventing DNA synthesis. By this virtue, MMC is an important antitumor drug. In addition, MMC has become the gold standard medication for glaucoma filtration surgery (GFS). This eye surgery creates a passage for drainage of aqueous humor (AqH) out of the eye into the sub-Tenon's space with the aim of lowering the intraocular pressure. A major cause of failure of this operation is fibrosis and scarring in the sub-Tenon's space, which will restrict AqH outflow. Intraoperative application of MMC during GFS has increased GFS success rate, presumably mainly by reducing fibrosis after GFS. However, still 10% of glaucoma surgeries fail within the first year. Recent findings In this review, we evaluate risks and benefits of MMC as an adjuvant for GFS. In addition, we discuss possible improvements of its use by adjusting dose and method of administration. Summary One way of improving GFS outcome is to prolong MMC delivery by using a drug delivery system.

The invention of poly(styrene-block-isobutylene-block-styrene) (“SIBS”) was the genius of Joseph P. Kennedy at the University of Akron (Akron, OH, United States). SIBS has no cleavable groups, and its predominantly alternating secondary and quaternary backbone prevents embrittlement and cracking under flexion. This chapter explores four medical devices enabled by SIBS: (1) the world’s most successful drug-eluting stent (TAXUS, Boston Scientific Corporate Research, Marlboro, MA, United States) releases the drug paclitaxel from a SIBS carrier that prevents restenosis by minimizing smooth muscle cell proliferation; (2) the discovery that SIBS provokes insignificant inflammation and encapsulation in the eye led to the development of the PRESERFLO MicroShunt (Santen Pharmaceutical Co. Ltd., Osaka, Japan) to lower intraocular pressure and stop the progression of vision loss from glaucoma; (3) Xi’an EyeDeal Medical Technology Co., Ltd. (Xi’an, China) is developing crosslinked polyisobutylene as an intraocular lens that eliminates glistening and halos; and (4) Polynova Cardiovascular Inc. (Stony Brook, NY, United States) is testing crosslinked SIBS as a heart leaflet valve to allow percutaneous implantation of heart valves in a diverse group of patients.

Trabeculectomy remains the ‘gold standard’ intraocular pressure (IOP)-lowering procedure for moderate-to-severe glaucoma; however, this approach is associated with the need for substantial post-operative management. Micro-invasive glaucoma surgery (MIGS) procedures aim to reduce the need for intra- and post-operative management and provide a less invasive means of lowering IOP. Generally, MIGS procedures are associated with only modest reductions in IOP and are targeted at patients with mild-to-moderate glaucoma, highlighting an unmet need for a less invasive treatment of advanced and refractory glaucoma. The PRESERFLO® MicroShunt (formerly known as InnFocus MicroShunt) is an 8.5 mm-long (outer diameter 350 μm; internal lumen diameter 70 μm) glaucoma drainage device made from a highly biocompatible, bioinert material called poly (styrene-block-isobutylene-block-styrene), or SIBS. The lumen size is sufficiently small that at normal aqueous flow hypotony is avoided, but large enough to avoid being blocked by sloughed cells or pigment. The MicroShunt achieves the desired pressure range in the eye by draining aqueous humor from the anterior chamber to a bleb formed under the conjunctiva and Tenon’s capsule. The device is implanted ab externo with intraoperative Mitomycin C via a minimally invasive (relative to incisional surgery) surgical procedure, enabling precise control of placement without the need for gonioscopy, suture tension control, or suture lysis. The implantation procedure can be performed in combination with cataract surgery or as a standalone procedure. The MicroShunt received Conformité Européenne (CE) marking in 2012 and is intended for the reduction of IOP in eyes of patients with primary open-angle glaucoma in which IOP remains uncontrolled while on maximum tolerated medical therapy and/or in which glaucoma progression warrants surgery. Three clinical studies assessing the long-term safety and efficacy of the MicroShunt have been completed; a Phase 3 multicenter, randomized clinical study comparing the MicroShunt to primary trabeculectomy is underway. In preliminary studies, the MicroShunt effectively reduced IOP and use of glaucoma medications up to 3 years after implantation, with an acceptable safety profile. This article summarizes current literature on the unique properties of the MicroShunt, the preliminary efficacy and safety findings, and discusses its potential use as an alternative to trabeculectomy for glaucoma surgery.

Aims An observational study to determine the safety and efficacy of filtering surgery employing a microlumen aqueous drainage device (InnFocus MicroShunt), used intraoperatively with Mitomycin C, implanted alone or in combination with phacoemulsification. Materials and methods Single-site, prospective, nonrandomized study of 23 eyes that had failed maximum tolerated glaucoma medication, followed for 3 years. A MicroShunt was implanted ab externo through a needle tract under the limbus, draining aqueous from the anterior chamber to the scleral surface. Prespecified outcome measures include: intraocular pressure (IOP) control, with and without supplemental medication, success rate, medication use, and adverse events. Results Fourteen patients received the MicroShunt alone and 9 with cataract surgery. At 1 (n=23), 2 (n=22), and 3 (n=22) years of follow-up; the qualified success rate (IOP ≤ 14 mm Hg and IOP reduction ≥ 20%) was 100%, 91%, and 95%; mean medicated IOP was reduced from 23.8 ± 5.3 to 10.7 ± 2.8, 11.9 ± 3.7, and 10.7 ± 3.5 mm Hg, and the mean number of glaucoma medications/patient was reduced from 2.4 ± 0.9 to 0.3 ± 0.8, 0.4 ± 1.0, and 0.7 ± 1.1, respectively. The most common complications were transient hypotony (13%, 3/23) and transient choroidal effusion (8.7%, 2/23), all resolved spontaneously. There were no leaks, infections, migrations, erosions, persistent corneal edema, or serious long-term adverse events. Conclusion Surgery with the InnFocus MicroShunt transscleral aqueous drainage tube with Mitomycin C achieved IOP control in the low teens in most subjects up to 3 years of follow-up with only transient adverse events occurring within the first 3 months after surgery.

Glaucoma is the second leading cause of blindness with ∼70 million people worldwide who are blind from this disease. The currently practiced trabeculectomy surgery, the gold standard treatment used to stop the progression of vision loss, is rather draconian, traumatic to the patient and requires much surgical skill to perform. This article summarizes the more than 10‐year development path of a novel device called the InnFocus MicroShunt®, which is a minimally invasive glaucoma drainage micro‐tube used to shunt aqueous humor from the anterior chamber of the eye to a flap formed under the conjunctiva and Tenon's Capsule. The safety and clinical performance of this device approaches that of trabeculectomy. The impetus to develop this device stemmed from the invention of a new biomaterial called poly(styrene‐block‐isobutylene‐block‐styrene), or “SIBS.” SIBS is ultra‐stable with virtually no foreign body reaction in the body, which manifests in the eye as clinically insignificant inflammation and capsule formation. The quest for an easier, safer, and more effective method of treating glaucoma led to the marriage of SIBS with this glaucoma drainage micro‐tube. This article summarizes the development of SIBS and the subsequent three iterations of design and four clinical trials that drove the one‐year qualified success rate of the device from 43% to 100%. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 211–221, 2017.

BACKGROUND AND OBJECTIVE: To assess the biocompatibility and intraocular pressure (IOP) lowering effect of a novel glaucoma drainage implant in rabbits. MATERIALS AND METHODS: Sixteen New Zealand white rabbits received one of three glaucoma drainage implants fabricated from poly-(styrene-b-isobutylene-b-styrene [SIBS]) with an internal diameter of the lumen of either 70 (6 eyes), 100 (6 eyes), or 150 (4 eyes) μm. Clinical follow-up examinations were performed during 6 months and postmortem eyes were studied with light microscopy. RESULTS: Smaller internal diameter implants were associated with fewer complications. IOP levels were not statistically different among the groups. No eyes developed serious complications. Mild chronic inflammation was observed around the tube using light microscopy. CONCLUSION: SIBS glaucoma drainage implants did not produce clinically detectable intraocular inflammation in a rabbit model. The 70- and 100-μm SIBS drainage devices demonstrated fewer postoperative complications. IOP levels were not statistically different from control eyes in all groups.

Trileaflet polymeric prosthetic aortic valves (AVs) produce hemodynamic characteristics akin to the natural AV and may be most suitable for applications such as transcatheter implantation and mechanical circulatory support (MCS) devices. Their success has not yet been realized due to problems of calcification, durability, and thrombosis. We address the latter by comparing the platelet activation rates (PARs) of an improved polymer valve design (Innovia LLC) made from poly(styrene-block-isobutylene-block-styrene) (SIBS) with the commercially available Carpentier-Edwards Perimount Magna Aortic Bioprosthetic Valve. We used our modified prothrombinase platelet activity state (PAS) assay and flow cytometry methods to measure platelet activation of a pair of 19 mm valves mounted inside a pulsatile Berlin left ventricular assist device (LVAD). The PAR of the polymer valve measured with the PAS assay was fivefold lower than that of the tissue valve (p 0.005) and fourfold lower with flow cytometry measurements (p 0.007). In vitro hydrodynamic tests showed clinically similar performance of the Innovia and Magna valves. These results demonstrate a significant improvement in thrombogenic performance of the polymer valve compared with our previous study of the former valve design and encourage further development of SIBS for use in heart valve prostheses. ASAIO Journal 2011; 57:26‐31.

Polymer heart valves have been under investigation since the 1960s, but their success has been hampered by an overall lack of durability mainly due to calcification of the leaflets and a relatively high rate of thromboembolic complications. A new polymer (Quatromer) trileaflet design was tested for its thrombogenic potential and was compared to that of existing prosthetic heart valves routinely implanted in patients: a St. Jude Medical bileaflet mechanical heart valve (MHV) and a St. Jude porcine bioprosthetic tissue valve. The valves were mounted in a left ventricular assist device and the procoagulant activity of the platelets was measured using a platelet activation state (PAS) assay. The PAS measurements indicated that the platelet activation level induced by the polymeric valve was very similar to that induced by the St. Jude Medical MHV and the St. Jude tissue valve. No significant difference was observed between the three valves, indicating that they have a comparable thrombogenic potential.

Recurrent or intractable ureteral strictures pose a significant problem for the practicing urologist. Metallic stents have been used sparingly for this problem with varying success. We investigated the use of a stent-graft consisting of a metal stent lined with a porous biocompatible polymer to determine if the liner would prevent urothelial ingrowth. One ureter of each of 11 dogs was treated with either a metallic woven stent or stent-graft inserted retrograde via a midline cystotomy. Six bare wire stents (controls) and five lined with a new, porous, biocompatible, polycarbonate elastomer liner (Corethane [registered sign]) were placed. The animals were followed radiographically with intravenous urography (IVP) at 6 weeks and just prior to sacrifice (12 to 22 weeks). Gross, histological, and electron microscopic analyses were performed. The results demonstrate that all of the bare metal stented animals developed moderate to severe hydroureteronephrosis with significant urothelial hyperplasia and ...

Approximately 50,000 abdominal aortic aneurysms (AAAs) are surgically repaired annually in the United States. Endovascular grafts (EVGs) combine a stent and a vascular graft offering great potential for reduced morbidity, mortality, and hospital stay because of minimally invasive endoluminal placement through catheters. Because most AAAs extend into one or both iliac arteries, a bifurcated EVG (bEVG) was developed, consisting of a proximal aortic trunk divided into two distinct lumens or sockets to receive two smaller diameter leg (iliac) components. All components were composed of Didcott self-expanding braided wire stents integrally attached to porous spun polycarbonate urethane liners. Successful placement of the bEVGs (trunks 10- 12 mm and legs 5-6 mm diameter) by a 10 Fr introducer through the femoral arteries into the infrarenal aorta and external iliac arteries of 9 of 11 dogs was achieved. Subsequently, 11 of 12 bEVGs were successfully placed to exclude a saccular aneurysm exceeding three aortic diameters created by a fascia lata pouch extending from the aorta into the left external iliac artery, of which 7 were patent at 1 to 4 months. These findings establish design feasibility of the bEVG as well as the utility of the canine experimental model.

An important need in hemodialysis is a self-sealing prosthesis for vascular access with at least equivalent patency and biostability to expanded polytetrafluoroethylene (ePTFE) alternatives. The authors have developed a Corethane/polyester composite (CPC) graft with an inner blood interfacing layer of spun Corethane fibers (10-15 microns diameter; pore size 30-60 microns) impregnated with a gelatin-heparin complex and an outer soft tissue interfacing warp-knitted polyester sheath. Twenty-six CPC grafts (6 mm internal diameter; 25-30 cm length) and eight Gore-Tex ePTFE grafts (same dimensions) were implanted as femoral artery-to-vein shunts in dogs on low dose (162 mg/day) aspirin, and subjected to weekly dialysis needle punctures for up to 52 weeks. Patency was 73% (19/26 with 15 at 52 weeks) for the CPC grafts and 63% (5/8 at 52 weeks) for the ePTFE controls, with more favorable healing (e.g., less extensive mural thrombi) of the CPC grafts. The hemostasis time per needle pair after removal (3.1 min mean for CPC versus 21.2 min mean for ePTFE) and the blood loss in achieving hemostasis (5.7 g mean for CPC versus 47.9 g for ePTFE) documented the significant (p < 0.0001) performance advantages of the CPC prosthesis.

Calcific aortic valve disease (CAVD) is the most common and life threatening form of valvular heart disease, characterized by stenosis and regurgitation, which is currently treated at the symptomatic end-stages via open-heart surgical replacement of the diseased valve with typically either a xenograft tissue valve or mechanical heart valve. These options offer the clinician a choice between structural valve deterioration and anticoagulant therapy respectively, effectively replacing one disease with another [1]. Polymeric heart valves (PHV) offer the promise of reducing or eliminating these complications [2] and may be efficacious for patients who cannot tolerate cardiothoracic surgery by using instead transcatheter valve implantation (TAVI) [3], where there is evidence that tissue valves are damaged during implantation [4], and in pulsatile circulatory support devices such as the SynCardia Total Artificial Heart. But development of PHVs has been slow due to the lack of sufficiently durable and biocompatible formulations.Copyright © 2012 by ASME

Valvular heart disease (VHD) continues to be a significant public health issue with an estimated 1–2% of the population affected [1]. Currently, VDH is primarily treated at the end stages with open-heart surgical replacement of the diseased valve with either a tissue or mechanical prosthetic heart valve (PHV), each having deficiencies including low durability and high thrombosis respectively. Polymer trileaflet PHVs have been designed to mimic the native aortic valve (AV) hemodynamics while being more durable and less thrombogenic than current PHVs. Recent advances in polymers and its applications for polymer PHVs, including transcatheter PHVs or use in the Total Artificial Heart (TAH) (Fig. 1), encourage further research and development [2–4]. Paramount to polymer PHV progress is proving equivalence to commercially available FDA approved PHVs.

We have developed a composite vascular prosthesis with the inner blood interfacing layer made of a porous elastomeric membrane of spun Corethane fibers (10-15 microns in diameter, pore size 30-60 microns) impregnated with a gelatin-heparin complex and an outer soft tissue interfacing warp knitted Dacron sheath. Forty-eight Corethane/Dacron composite (CDC) vascular grafts, 4 mm in diameter and 5 cm in length, and 48 expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar size were implanted bilaterally as end to end interposition grafts on opposite sides in the carotid and femoral arteries in dogs on low dose (162 mg/day) aspirin. Patency at 3 months was 37/48 (77%) for the ePTFE grafts and 44/48 (91.7%) for the CDC grafts. Fisher's exact test (two-tailed comparison) indicates the probability of superior CDC graft patency to be 95.5%. In the seven pairs of grafts in which one graft was occluded and the contralateral graft of another type was patent, the CDC graft was patent and the ePTFE graft was occluded in every instance. Explant histology and scanning electron microscopy showed greater collagenization, less residual platelet-fibrin and red blood cell deposits, and more frequent mid-graft endothelialization in the CDC grafts than in the ePTFE grafts.

Purpose To evaluate the effectiveness of an orbital tissue expander designed to stimulate orbital bone growth in an anophthalmic socket. Design Retrospective, noncomparative, interventional case series. Methods settings: Institutional. study population: Nine consecutive patients with unilateral congenital anophthalmos. intervention: The orbital tissue expander is made of an inflatable silicone globe sliding on a titanium T-plate secured to the lateral orbital rim with screws. The globe is inflated by a transconjunctival injection of normal saline through a 30-gauge needle to a final volume of approximately 5 cm 3 . Computed tomography scans were used to determine the orbital volume. The data studied were: demographics, prior orbital expansion procedures, secondary interventions, orbital symmetry, and implant-related complications. main outcome measures: The primary outcome measure was the orbital volume change, and the secondary outcome measures were changes in forehead, brow, and zygomatic eminence contour and adverse events. Results The average patient age at implantation was 41.89 ± 39.42 months (range, 9 to 108 months). The initial average volume of inflation was 3.00 ± 0.87 cm 3 (range, 2.0 to 4.0 cm 3 ), and the average final volume of 4.33 ± 0.50 cm 3 (range, 4.0 to 5.0 cm 3 ) was achieved. The duration of expansion was 18.89 ± 8.80 months (range, 4 to 26 months). All patients demonstrated an average increase in the orbital tissue expander implanted orbital volume of 5.112 ± 2.173 cm 3 (range, 2.81 to 10.38 cm 3 ). The average difference between the volume of the implanted and the initial contralateral orbit was 5.68 ± 2.34 cm 3 , which decreased to 2.53 ± 1.80 cm 3 at the final measurement ( P t test). All implants remained inflated except for 2 iatrogenic punctures at the second inflation and 1 that was the result of implant failure. All were replaced. Conclusions The integrated orbital tissue expander is safe and effective in stimulating anophthalmic socket bone growth.

Implantation methods for commercially available heart valve prostheses require open-chest access to the heart to perform the suturing process. In order to alleviate this complicated surgical implant technique, a “stent-valve” design was developed that will provide a less cumbersome implantation method and therefore a less invasive access to the heart. The purpose of this study is to verify its hydrodynamic performance and migration characteristics to assess its feasibility for use as a replacement heart valve. Hydrodynamic evaluation of the novel stent-valve combination device was carried out using a Vivitro left heart simulator and by setting up a comparison with the same 19 mm trileaflet valve under a traditional implantation (suture) method. To assess implantation ability under normal physiological conditions, porcine aortic root tissue was mounted into the left heart simulator to replace the original glass sinus. A comparison experiment was conducted to study the change in the total compliance and resistance of the testing system using the modified Windkessel model. For the range of test conditions investigated, the stent-valve combination device produced an average pressure gradient of 41.2 mm Hg(±19.6 mm Hg), an average effective orifice area (EOA) of 1.06 cm2(±0.08 cm2), and an average regurgitation percentage of 4.5% (±3.3%), while the sutured valve produced an average pressure gradient of 48.7 mm Hg(±17.4 mm Hg), an average EOA of 0.88 cm2(±0.14 cm2), and an average regurgitation percentage of 0.8% (±0.4%). The total compliance and resistance of the system was 0.37 ml/mm Hg(±0.01 ml/mm Hg) and 1.1 mm Hg/ml/s(±0.29 mm Hg/ml/s), with the original Windkessel model, and 0.33 ml/mm Hg(±0.01 ml/mm Hg) and 1.1 mm Hg/ml/s(±0.24 mm Hg/ml/s) for the system with the aortic tissue. The stent-valve combination device has demonstrated favorable hydrodynamic performance when compared with the same trileaflet valve under the traditional suturing method, and the arterial stent makes it possible to secure the valve at its required position without migration.

A composite polymeric material, poly(styrene-block-isobutylene-block-styrene) (SIBS) with an embedded reinforcement polyethylene terephthalate (PET) fabric, is undergoing investigation for potential use in a novel heart valve. The purpose of this study was to develop and implement a small animal model to assess the biocompatibility of composite samples in a cardiovascular tissue and blood-contacting environment. Composite samples were manufactured using dip coating and solvent casting with two coating thicknesses (25 and 50 microm). A novel rat abdominal aorta model was developed to test the dip-coated samples in a similar pulsatile flow condition to its intended use, and both dip-coated and solvent-cast samples were tested using a rat subcutaneous model. Tissue response, defined by degree of cellular infiltration and encapsulation, was minimized when a smooth coating of SIBS shielded the PET fabric from exposure to blood and tissue, and the degree of tissue response was directly correlated with the degree of surface roughness. Surface modification using phospholipid further reduces the tissue response. We have demonstrated the applicability of using a novel rat abdominal aorta model for biocompatibility assessment of polymeric materials that will be used in cardiovascular implants. For the purpose of this study, our results indicate that solvent casting with a 25-microm SIBS coating thickness will provide optimal biocompatibility for the SIBS valve.

The novel trileaflet heart valve that is presently undergoing investigation is a composite design of a proprietary polymer (SIBS), with an embedded fabric. SIBS had been shown to be a biocompatible, oxidatively stable polymer, and by adopting the natural valve leaflet design (reinforcement fabric), the SIBS trileaflet valve has the potential to have outstanding hemodynamic performance, durability, and biocompatibility [1,2].Copyright © 2008 by ASME

Polymer trileaflet valves have been under investigation for the past 40–50 years in an attempt to produce a valve alternative that is both durable and non-thrombogenic. Most have met with limited success due to oxidative reactions and high dynamic stresses borne by the material [1]. With this knowledge, an oxidatively stable polyolefin, poly(styrene-b-isobutylene-b-styrene) (SIBS), was selected for the design of a fiber-reinforced polymer trileaflet heart valve. The hydrodynamic properties of prototype SIBS valves have been encouraging, but some valves failed prematurely as a result of insufficient durability during in vivo implantation in a sheep model or during accelerated in vitro fatigue.

Poly(Styrene-block-IsoButylene-block-Styrene) ("SIBS") is a biostable thermoplastic elastomer with physical properties that overlap silicone rubber and polyurethane. Initial data collected with SIBS stent-grafts and coatings on metallic stents demonstrate hemocompatibility, biocompatibility and long-term stability in contact with metal. SIBS has been used successfully as the carrier for a drug-eluting coronary stent; specifically Boston Scientific's TAXUS stent, and its uses are being investigated for ophthalmic implants to treat glaucoma, synthetic heart valves to possibly replace tissue valves and other applications. At present, researchers developing medical devices utilizing SIBS have found the following: (1) SIBS does not substantially activate platelets in the vascular system; (2) polymorphonuclear leukocytes in large numbers are not commonly observed around SIBS implants in the vascular system or in subcutaneous implants or in the eye; (3) myofibroblasts, scarring and encapsulation are not clinically significant with SIBS implanted in the eye; (4) embrittlement has not been observed in any implant location; (5) calcification within the polymer has not been observed; and (6) degradation has not been observed in any living system to date. Some deficiencies of SIBS that need to be addressed include creep deformation in certain load-bearing applications and certain sterilization requirements. The reason for the excellent biocompatibility of SIBS may be due to the inertness of SIBS and lack of cleavable moieties that could be chemotactic towards phagocytes.

Objective To report clinical evaluation, flow patency, and histopathological findings of a novel glaucoma drainage implant (GDI) made of poly(styrene-b-isobutylene-b-styrene) (SIBS) in rabbits. Methods In 16 normal eyes, the proximal end of the SIBS GDI was inserted into the anterior chamber while the distal end was placed in the subconjunctival space. A control group underwent implantation of a similarly designed silicone GDI. Slitlamp follow-up and intraocular pressure measurements were recorded. Flow patency was evaluated by injecting 0.01% fluorescein into the anterior chamber. Immunostaining against collagen IV, macrophages, and α smooth muscle actin was performed. Results Slitlamp examination suggested adequate biocompatibility. A low and diffuse bleb was observed in the SIBS group. All SIBS tubes were patent 6 months after insertion. Immunostaining demonstrated noncontinuous collagen deposition. No macrophages or myofibroblasts were visible around the SIBS tubes. In contrast, silicone induced collagen deposition and myofibroblast differentiation. Conclusion This new GDI is clinically biocompatible in the rabbit and maintained 100% patency at 6 months. A remarkable difference was the absence of myofibroblasts in the surrounding tissue in the SIBS group. Clinical Relevance This novel GDI made of SIBS would prevent the feared complication of hypotony and will decrease the amount of subconjunctival fibrosis.

A novel polyolefin, poly(styrene-b-isobutylene-b-styrene) (Quatromer™), is being proposed as a viable polymer for use in trileaflet heart valves because of its oxidative stability. The current study was designed to assess the polymer's hemocompatibility and mechanical durability. Mechanical characterization included static tensile tests and dynamic tension–tension and bending fatigue tests, where the properties of isotropic and composite (polypropylene (PP) embedded) Quatromer specimens were compared with those of a polyurethane (PUR) approved for cardiovascular applications. It was found that by embedding PP fibers into the Quatromer matrix, the tensile and fatigue properties of the polymer could be improved, making them comparable, if not better than the PUR. The thrombotic potential of Quatromer was compared with the PUR, glutaraldehyde-fixed porcine valve material, and a positive and negative control by measuring platelet deposition with radiolabeled platelets in a parallel plate flow configuration. The porcine valve material was found to have significantly higher platelet deposition under all flow regimes, while no significant difference existed between Quatromer and PUR. In conclusion, Quatromer is shown to have suitable hemocompatibility and mechanical durability for use in polymer trileaflet heart valves, and fiber reinforcement can effectively be used to tailor the mechanical properties. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006

Purpose: To demonstrate the biocompatibility of SIBS implants as compared to PDMS implants in the treatment of retinal detachment in New Zealand White (NZW) rabbit model.1,2 Introduction: Scleral encircling bands, fixation rings and buckles are utilized for closure of retinal breaks and retina reattachment. The FDA approved PDMS-implant is associated with several post-operative complications, involving thick-fibrotic encapsulations. SIBS, an elastomeric triblock copolymer, was recently FDA approved for use in a cardiovascular drug eluting stent (TAXUSTM, Boston Scientific Corp., MA) and showed excellent biocompatibility and slow drug release capability. Materials and Methods: SIBS (9-mol%-styrene) implants were fabricated (InnFocus LLC, USA) to match PDMS implants (Labtician, Inc, Canada) dimensions. 5 NZW rabbits received SIBS and 4, PDMS-implants. Post-operative exam sequence: day 1 and 2, week 1, 2, 3, 4 and 6, and monthly thereafter for up to 1 year. Anatomohistopathology exams sequence: one SIBS animal at 6 weeks and one animal of each treatment group at 3 and 6-months, and two at 12-months. Results: SIBS compared to PDMS animals exhibited less inflammation and a better buckling effect during the first 6 weeks. At POD 9 months, the conjunctival injection in the SIBS rabbit was none as opposed to the PDMS value and the buckling effect for both groups were equal. There were no visible signs of encapsulation with SIBS. There were no infections in the 9 animals and none of the implants extruded thus far (

Purpose: To assess the efficacy of a novel orbital tissue expander (OTE) in treating congenital anophthalmic and microphthalmic infants. Methods: The OTE implant is an inflatable (0.5 to >6cc) silicone rubber globe sliding on a titanium T-shaped bone plate secured to the temporal bone with 1mm titanium screws. In vitro testing was performed to assess injection volume versus diameter measurements to determine consistency between devices, flex fatigue for durability of the implants when compressed, weight change in isotonic saline at 37°C to mimic human body temperature, seal durability by puncturing the globe numerous times while inflating, capacity before rupture to determine the maximum amount of saline it is able to contain, and effective sterilization. Ex-vivo testing was performed for adjustments prior to in vivo study. An OTE was then implanted in five 2-week old kittens (OS only) and inflated in 0.5cc increments. Three control animals received enucleation alone. All 8 animals were followed for 18 weeks and underwent euthanasia for morphological and histopathological analysis. Results: In vitro testing confirmed a

Purpose: To design and test the Miami-InnFocus Drainage Implant (MiDi) as a glaucoma shunt that is biocompatible, flexible, and significantly smaller than existing commercial implants in order to prevent postoperative hypotony, inflammation, scarring, erosion, and extrusion. Methods: A new biomaterial composed of styrene-b-isobutylene-b-styrene (SIBS) was used in a novel design for a glaucoma drainage implant. The implant consists of a tube 11mm long with an inner diameter of 70, 100, and 150 μm and outer diameter of 250 μm with a 1mm 2 tab located 4.5mm from the proximal tip to prevent migration. The device was implanted in 15 New Zealand White rabbits for biocompatibility and efficacy testing. A similarly designed implant made of polydimethylsiloxane was implanted in 6 other animals as a pseudo-control. Typical GDI implantation technique was modified for this device. The proximal end of the new SIBS implant was inserted 2mm into the anterior chamber and the distal end placed in a subconjunctival space created by the surgeon. Biocompatibility of the device was studied by slit-lamp follow-up and intraocular pressure (IOP) measurements recorded periodically. Results: Biocompatibility of the MiDi was excellent. A low and diffuse bleb was observed with these devices. All SIBS tubes were patent 9 months after insertion. Immunostaining demonstrated non-continuous deposition of collagen with virtually no encapsulation. No macrophages or myofibroblast were visible around the SIBS polymer which was found more bioinert than the control PDMS. Conclusion: This newly designed glaucoma implant is clinically biocompatible in the rabbit model and maintained 100% patency at 9 months.

Heart valve prostheses have been used successfully since 1960 and generally result in improvement in the longevity and symptomatology of patients with valvular heart disease. However, NIH’s Working Group on Heart Valves reports that 10-year mortality rates still range from 30–55%, and that improvements in valve design are required to minimize thrombotic potential and structural degradation and to improve morbidity and mortality outcomes.

Purpose To evaluate the anatomical effects and tissue biocompatibility in a feline model of an integrated orbital tissue expander (OTE) designed to stimulate bone growth in an anophthalmic socket. Design An animal study was performed in cats to assess orbital bone growth with and without an OTE. Methods The OTE is an inflatable (0.5 to >6.0 cm 3 ) polymeric globe sliding on a titanium T plate secured to the lateral orbital rim with screws. Eight cats had left eye enucleation at age two weeks, with five orbits receiving an OTE and the remaining three serving as nonimplanted controls. Serial transconjunctival implant inflation was performed by injecting normal saline solution into the OTE to a final volume of 3.5 ml. Serial computed tomographic scans were obtained to assess socket growth. All eight cats were euthanized at 18 weeks and dry skulls prepared. The effective orbital volume was measured by inflating an OTE in the orbit of a dry skull until it filled the cavity completely. Results Three cats periodically scratched open the tarsorrhaphy and conjunctiva to rupture the OTE, which resulted in implant exchanges. At 18 weeks, the OTE expanded orbital volume was approximately 18% smaller than the normal contralateral side. In the control animals, the anophthalmic orbital volume was approximately 66% smaller than the contralateral orbit. Histopathology of orbital tissues showed no evidence of foreign body reaction. Conclusions This proof-of-concept pilot study demonstrated implant efficacy in cats, and no implant-related adverse effects were observed. OTE has the potential to stimulate bone growth in human anophthalmic orbits.

Work reported here shows that, contrary to reports in the literature, hydrogels made from pure poly(2-hydroxyethyl methacrylate), pHEMA, at crosslinker content greater than 0.15 mol % do not swell above the usual equilibrium values of 39-42% water content in aqueous urea solution. However, hydrogels containing small (impurity) amounts of methacrylic acid (MAA) do swell dramatically (approximately 90%) in dilute urea solution, but not directly due to the urea. The urea decomposes to produce ammonium ions, thus raising the pH of the solution. Ionization of MAA occurs above pH 6, causing electrostatic interactions within the gel. The grossly swollen state of these gels represents an internal equilibrium among forces due to rubber elasticity, polymer-polymer/solvent affinity, and electrostatic interactions.

The effects of low levels of methacrylic acid (MAA) (less than 4 mol %) and a crosslinker (less than 0.3 mol %) on the equilibrium swelling and water content of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels were investigated. Numerous pHEMA disks, some of which were doped with small amounts of MAA, were placed in swelling baths simulating possible urological as well as physiological conditions. Several interesting facts are reported, such as, in dilute urea (0.15M) or in alkali solution, gels containing 2% MAA are capable of swelling to 3600% their size in mild acid, saline, or distilled water, with associated water contents that range as high as 98%. Also, gels containing small amounts of MAA and finite crosslinker content can be made that are soluble in mild urea or alkali solution. The significance of this study is that gels or gel surfaces can be fabricated that are highly responsive to their environment. In addition, since the level of MAA that cause this shrink–swell behavior are well within the impurity levels of MAA found in unpurified commercial HEMA, it is conceivable that this shrink–swell behavior may have occurred in early studies of implanted pHEMA gels, thus confusing the subsequent evaluation of its performance as a biomaterial.

Hydrogel prostheses made of poly(2-hydroxyethyl methacrylate), pHEMA, have demonstrated resistance to calcification in the urinary tract(1–3). Implantation studies in non-urinary locations suggest that the methacrylic acid, MAA, content in these gels plays a critical role in their calcification resistance(4,5) and hence may be important for urine compatibility. It is well known that the equilibrium water content and other properties of the gel change significantly according to MAA content(6). Our work, presented here and elsewhere(7,8), shows that gels fabricated with small amounts of MAA and with low crosslinker content demonstrate a reversible shrink/swell behavior. The swollen volume or water content of these gels is highly dependent on electrolyte, pH, or urea contents of the test solutions. In response to a small change in the local environment the shrink/swell behavior may cause volume changes as large as seven hundred percent (largest swollen volume/smallest swollen value) and can occur quite rapidly for thin geometries. The responsive shrink/swell behavior occurs within the normal range of urine composition.