Hydrogel Implants Research Articles

Augmentation of Left Ventricular Wall Thickness With Alginate Hydrogel Implants Improves Left Ventricular Function and Prevents Progressive Remodeling in Dogs With Chronic Heart Failure

The study tested the hypothesis that augmentation of the left ventricular (LV) wall thickness with direct intramyocardial injections of alginate hydrogel implants (AHI) reduces LV cavity size, restores LV shape, and improves LV function in dogs with heart failure (HF). Progressive LV dysfunction, enlargement, and chamber sphericity are features of HF associated with increased mortality and morbidity. Studies were performed in 14 dogs with HF produced by intracoronary microembolizations (LV ejection fraction [EF] <30%). Dogs were randomized to AHI treatment (n = 8) or to sham-operated control (n = 6). During an open-chest procedure, dogs received either intramyocardial injections of 0.25 to 0.35 ml of alginate hydrogel (Algisyl-LVR, LoneStar Heart, Inc., Laguna Hills, California) or saline. Seven injections were made ∼ 1.0 to 1.5 cm apart (total volume 1.8 to 2.1 ml) along the circumference of the LV free wall halfway between the apex and base starting from the anteroseptal groove and ending at the posteroseptal groove. Hemodynamic and ventriculographic measurements were made before treatment (PRE) and repeated post-surgery for up to 17 weeks (POST). Compared to control, AHI significantly reduced LV end-diastolic and end-systolic volumes and improved LV sphericity. AHI treatment significantly increased EF (26 ± 0.4% at PRE to 31 ± 0.4% at POST; p < 0.05) compared to the decreased EF seen in control dogs (27 ± 0.3% at PRE to 24 ± 1.3% at POST; p < 0.05). AHI treatment was well tolerated and was not associated with increased LV diastolic stiffness. In HF dogs, circumferential augmentation of LV wall thickness with AHI improves LV structure and function. The results support continued development of AHI for the treatment of patients with advanced HF.

In vitro and in vivo efficacy of doxorubicin loaded biodegradable semi-interpenetrating hydrogel implants of poly (acrylic acid)/gelatin for post surgical tumor treatment

The paper describes the preparation and evaluation of doxorubicin loaded semi-interpenetrating polymeric hydrogel network of polyacrylic acid (PAc) and gelatin (G). Post surgical antitumor efficacy and biodistribution of doxorubicin from the implanted degradable hydrogels was investigated on Ehrlich's ascites tumor model using albino mice. Polycaprolactone diacrylate (PCL-DAr) was employed as a crosslinking agent for PAc chains whereas G was kept free. The effect of crosslinking concentration on various physico-chemical properties such as thermal behavior, swelling, degradation behavior, drug release and polymer–polymer interactions was investigated by various physico-chemical tools. Semi-interpenetrating polymeric networks (IPNs) with 0.2 mol% crosslinking concentration showed degradation within 20 days in phosphate buffer (pH 6.5). To determine the in vivo anticancer efficacy, placebo and drug laden cylindrical implants (65 ± 5 µg/implant of 10 mg) were implanted in tumor cavity post tumor excision. After predetermined time intervals (day 7, 11, 14, 20 and 25), drug biodistribution was assessed in tumor, tumor periphery, residual hydrogel and all vital organs i.e. liver, spleen, kidney, heart, lung and blood (spectrofluorimetrically). The drug distribution study showed the concentration of drug in the tumor, tumor periphery and residual hydrogel decreased with increasing time; on the 7th day, drug concentration was highest while, on the 25th day, it was negligible; however, insignificant quantities of the drug was found in vital organs. Histological examination revealed no sign of tumor recurrence until the 25th day with 100% necrosis and slight inflammation in treated the group. In vivo results established that these biodegradable implants can be utilized as post surgical therapy for solid tumors.

Rupture of Breast Implants after Augmentation Mammoplasty: A Case Report of Simultaneous Intra-extracapsular Rupture

This paper presents the case of a ruptured hydrogel breast implant, along with its clinical, radiologic, and pathologic findings. Breast asymmetry is typically the most common clinical feature of breast implant rupture. In case of a hydrogel breast implant rupture, hydrogel spreads out after implant leakage and the breast is enlarged with swelling and edema. Intracapsular ruptures showed no significant collapse of the implants despite a collection of fluid surrounding the implant inside the capsule. However, extracapsular ruptures showed implant collapse and extensive inflammation or fibrosis extension to the muscle and chest wall. In this case, a large amount of fluid collection with enlarged implants inside the capsule and extracapsular granulomas were showed simultaneously. Since the use of silicone breast implants has been restricted, hydrogel implants have been used for some time as an alternative option for breast implants. However, hydrogel implants have been restricted because of their unpredictability and unreliability. This case report draws attention to an unusual presentation of complications following the insertion of hydrogel breast implants for augmentation mammoplasty. (Archives of Aesthetic Plastic Surgery 19: 81, 2013)

Injectable in situ-forming hydrogel for cartilage tissue engineering.

Methoxy polyethylene glycol-poly(ε-caprolactone) (MPEG-PCL; MP) diblock copolymers undergo a solution-to-gel phase transition at body temperature and serve as ideal biomaterials for drug delivery and tissue engineering. Here, we examined the potential use of a chondrocyte-loaded MP solution as an injectable, in situ-forming hydrogel for cartilage regeneration. The chondrocyte-MP solution underwent a temperature-dependent solution-to-gel phase transition in vitro, as shown by an increase in viscosity from 1 cP at 20-30 °C to 1.6 × 105 cP at 37 °C. The chondrocytes readily attached to and proliferated on the MP hydrogel in vitro. The chondrocyte-MP solution transitioned to a hydrogel immediately after subcutaneous injection into mice, and formed an interconnected pore structure required to support the growth, proliferation, and differentiation of the chondrocytes. The chondrocyte-MP hydrogels formed cartilage in vivo, as shown by the histological and immunohistochemical staining of glycosaminoglycans, proteoglycans, and type II collagen, the major components of cartilage. Cartilage formation increased with hydrogel implantation time, and the expression of glycosaminoglycans, and type II collagen reached maximal levels at 6 weeks post-implantation. Collectively, these data suggest that in situ-forming chondrocyte-MP hydrogels have potential as non-invasive alternatives for tissue-engineered cartilage formation.

Novel Saccharide-Peptide Hydrogel for Islet Transplantation and Long-Term Culture

The liver site currently utilized for islet tranplsantation is suboptimal for the reversal of type 1 diabetes (T1D). A rapid loss of transplanted islets, caused by slow revascularization and inflammation followed by a chronic decline of islet function is the primary cause of the poor prognosis. We have developed a novel Saccharide-Peptide (SP) hydrogel for improving islet transplantation in vivo, as well as for long-term islet culture in vitro, by providing an extracellular matrix support to islets. SP hydrogel offers unique properties such as biocompatibility, easy to handle, crosslinks at physiological conditions in the presence of suspended cells, and is easily injected before polymerization to desired sites. We first investigated the compatibility of this hydrogel with INS-1 cells cultured in monolayer. These cells did not exhibit measurable cell death after exposure to soluble polymer components (0.1 - 1 mg/mL). Histological sections of a SP hydrogel implantation site 13 days after transplantation contained no cellular infiltration within the hydrogel, and only a few mononuclear cells detected in some adjacent areas. Freshly-isolated rat or human islets cultured in hydrogel maintained a 3D structure, insulin release and strong dithizone staining for more than 28 days. Islets cultured in hydrogel responded to high glucose stimulation, indicating the diffusion of nutrients, glucose, and insulin across the barrier of the SP hydrogel. Control islets cultured in suspension for the same period lost 3D structure, released no insulin and did not stain with dithizone. Transplantation of encapsulated syngeneic islets under the kidney capsule reversed hyperglycemia, indicating the ability of the hydrogel to support islet viability and function once transplanted. These results demonstrated the hydrogel's ability to prevent islet aggregation, as well as maintain islet structure, viability and function in vitro and in vivo. In conclusion, the SP hydrogel is a promising synthetic encapsulation scaffold for the long-term maintenance of quality islets both in vitro and in vivo. This novel hydrogel can serve as a scaffold for islet transplantation and facilitate islet transplantation into extrahepatic sites.

Late Complications of Hydrogel Scleral Buckle Implants and a Technique for Effective Removal

The aim of this article is to describe complications of hydrogel (MIRAgel) scleral buckle implants that may appear many years after implantation, and to describe an effective technique to facilitate safe removal of these implants, which become extremely friable with time. Four case reports of patients with complications of hydrogel orbital implants and a technique for removal of the implants are described with review of the literature. The technique involves a conjunctival incision into each involved quadrant, followed by use of blunt instrumentation for "push" and a Frasier suction handpiece for "pull" to allow segmental removal. This technique limits the tendency of the implant to fragment, which has been a problem described with previous techniques. Cases typically present simulating an orbital tumor or infection, with the diagnosis not immediately apparent, as was the case in 3 of 4 cases in our series. The technique we used allowed for expeditious removal and prompt recovery in all 4 patients. Hydrogel scleral buckle implants can produce late complications that may be difficult to diagnose and manage. The "push-pull" technique described in this article facilitates effective removal, and may have implications for other types of orbital hydrogel implants as well.

A Subcutaneous Octreotide Hydrogel Implant for the Treatment of Acromegaly

To evaluate the pharmacokinetics, efficacy, and safety of a subcutaneous octreotide hydrogel implant in patients with acromegaly. In 2 phase II open-label randomized studies, patients aged ≥ 18 years with confirmed acromegaly and octreotide responsiveness received one or two 52 mg hydrated implants (52 mg study) or a hydrated or nonhydrated 84 mg implant (84 mg study) inserted subcutaneously in the upper arm. Implants were removed after 6 months. The 84 mg study assessed pharmacokinetics in patients with undetectable baseline octreotide concentrations. Both studies assessed efficacy (serum growth hormone [GH], insulin-like growth factor 1 [IGF-1]) and safety (adverse events, physical examination, clinical chemistry). Eleven patients received 1 (n = 5) or 2 (n = 6) 52 mg implants; 34 received a hydrated (n = 17 [safety]; n = 16 [efficacy analysis]) or nonhydrated (n = 17) 84 mg implant. With the nonhydrated versus hydrated 84 mg implant, mean maximum serum concentration (Cmax) and mean area under the drug concentration versus time curve from time 0 to 6 months were decreased (P = 0.002 and P = 0.03, respectively) and mean time to Cmax was increased (P = 0.002). In both studies, IGF-1 and GH declined in month 1 and were significantly suppressed during the 6-month treatment versus baseline (P<0.001). With the 52 mg and 84 mg implants, respectively, 3 of 11 patients (27%) and 17 of 33 patients (52%) achieved IGF-1 normalization and 8 of 11 patients (73%) and 13 of 33 patients (39%) exhibited GH <2.5 ng/mL; 9 of 11 patients (82%) and 11 of 34 patients (32%) experienced treatment-related adverse events, which were mainly gastrointestinal. Octreotide hydrogel implants were well tolerated and maintained stable octreotide release and suppression of IGF-1 and GH over 6 months.

Effects of recombinant human bone morphogenic protein‐2 and human bone marrow‐derived stromal cells on in vivo bone regeneration of chitosan–poly(ethylene oxide) hydrogel

In vivo bone regeneration of chitosan-poly(ethylene oxide) (PEO) hydrogel in rat carlvarial defects was evaluated by using both human bone marrow-derived stromal cells (hMSCs) and recombinant human bone marrow protein-2 (rhBMP-2) for 4 and 8 weeks. In situ chitosan-PEO hydrogel was fabricated by mixing the precursor solutions of both chitosan-acrylate and PEO-thiol. Fabrication of the injectable hydrogels was modulated from within a minute to hours by controlling the temperature and pHs of the precursor solution. Gel swellings were dependent on the conditions of pHs and temperatures of the precursor solutions, showing higher gel swelling in basic water than in either acidic or neutral water. The compression strengths and in vitro degradation of hydrogels were also evaluated by controlling the concentrations of both precursor solutions and lysozyme, respectively, by referencing to the morphology of the control hydrogel with no enzyme added. Hydrogels showed sustained release of rhodamine-B over time. After implantation of the injectable hydrogels in rat calvarial defects for 4 and 8 weeks, in vivo bone regenerations were compared with by evaluating the degrees of new bone formations with Soft X-ray, microcomputed tomography, and histological stainings of hematoxylin and eosine Y and Masson's trichrome. Degrees of in vivo bone regeneration were controlled by encapsulating in advance either hMSCs, rhBMP-2, or both in the precursor solutions of the hydrogel. The defect implanted with hydrogel only showed higher amount of bone tissue regeneration than that of the control defect site. The defect sites with hydrogel containing both hMSCs and rhBMP-2 demonstrated highest amount of bone tissue regeneration among the samples.

An Injectable Nucleus Pulposus Implant Restores Compressive Range of Motion in the Ovine Disc

Investigation of injectable nucleus pulposus (NP) implant. To assess the ability of a recently developed injectable hydrogel implant to restore nondegenerative disc mechanics through support of NP functional mechanics. Although surgical intervention for low back pain is effective for some patients, treated discs undergo altered biomechanics and adjacent levels are at increased risk for accelerated degeneration. One potential treatment as an alternative to surgery for degenerated disc includes the percutaneous delivery of agents to support NP functional mechanics. The implants are delivered in a minimally invasive fashion, potentially on an outpatient basis, and do not preclude later surgical options. One of the challenges in designing such implants includes the need to match key NP mechanical behavior and mimic the role of native nondegenerate NP in spinal motion. The oxidized hyaluronic acid gelatin implant material was prepared. In vitro mechanical testing was performed in mature ovine bone-disc-bone units in 3 stages: intact, discectomy, and implantation versus sham. Tested samples were cut axially for qualitative structural observations. Discectomy increased axial range of motion (ROM) significantly compared with intact. Hydrogel implantation reduced ROM 17% (P < 0.05) compared with discectomy and returned ROM to intact levels (ROM intact 0.71 mm, discectomy 0.87 mm, postimplantation 0.72 mm). Although ROM for the hydrogel implant group was statistically unchanged compared with the intact disc, ROM for sham discs, which received a discectomy and no implant, was significantly increased compared with intact. The compression and tension stiffness were decreased with discectomy and remained unchanged for both implant and sham groups as expected because the annulus fibrosus was not repaired. Gross morphology images confirmed no ejection of NP implant. An injectable implant that mimics nondegenerate NP has the potential to return motion segment ROM to normal subsequent to injury.

Localized controlled release of stratifin reduces implantation-induced dermal fibrosis

Localized controlled release of anti-fibrogenic factors can potentially prevent tissue fibrosis surrounding biomedical prostheses, such as vascular stents and breast implants. We have previously demonstrated that therapeutic intervention with topically applied stratifin in a rabbit ear fibrotic model not only prevents dermal fibrosis but also promotes more normal tissue repair by regulating extracellular matrix deposition. In this work, the anti-fibrogenic effect of a controlled release form of stratifin was investigated in the prevention of fibrosis induced by dermal poly(lactic-co-glycolic acid) (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel implants. Pharmacodynamic effects were evaluated by histopathological examination of subcutaneous tissue surrounding implanted composites. Controlled release of stratifin from PLGA microsphere/PVA hydrogel implants significantly moderated dermal fibrosis and inflammation by reducing collagen deposition (30%), total tissue cellularity (48%) and infiltrated CD3+ immune cells (81%) in the surrounding tissue compared with the stratifin-free implants. The controlled release of stratifin from implants markedly increased the level of matrix metalloproteinase-1 expression in the surrounding tissue, which resulted in less collagen deposition. These stratifin-eluting PLGA/PVA composites show promise as coatings to decrease the typical fibrosis exhibited around implanted biomedical prostheses, such as breast implants and vascular stents.

Hydrogels for nucleus replacement—Facing the biomechanical challenge

Hydrogels are considered promising for disc regeneration strategies. However, it is currently unknown whether the destruction of the natural interface between nucleus and surrounding structures caused by nucleotomy and an inadequate annulus closure diminishes the mechanical competence of the disc. This in vitro study aimed to clarify these mechanisms and to evaluate whether hydrogels are able to restore the biomechanical behaviour of the disc.Nucleus pressure in an ovine intervertebral disc was measured in vivo during day and night and adapted to an in vitro axial compressive diurnal (15min) and night (30min) load. Effects of different defects on disc height and nucleus pressure were subsequently measured in vitro using 30 ovine motion segments. Following cases were considered: intact; annulus incision repaired by suture and glue; annulus incision with removal and re-implantation of nucleus tissue; and two different hydrogels repaired by suture and glue.The intradiscal pressure in vivo was 0.75MPa during day and 0.5MPa during night corresponding to an in vitro axial compressive force of 130 and 58N, respectively. The compression test showed that neither the implantation of hydrogels nor the re-implantation of the natural nucleus, assumed as being the ideal implant, was able to restore the mechanical functionality of an intact disc.Results indicate the importance of the natural anchorage of the nucleus with its surrounding structures and the relevance of an appropriate annulus closure. Therefore, hydrogels that are able to mimic the mechanical behaviour of the native nucleus may fail in restoring the mechanical behaviour of the disc.

Novel Strategy for the Control of Postoperative Pain

The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is the most common nonopioid analgesic currently used for postoperative pain management. We tested the sustained analgesic effect of ketoprofen emanating from a biodegradable gelatin hydrogel in a rat model of postoperative pain. A sheet of analgesic-infiltrated hydrogel was inserted below the plantaris muscle at the end of surgery. Mechanical thresholds were measured by use of von Frey filaments before and 2 weeks after the operation. The effect of ketoprofen on the postoperative pain was also assessed immunohistochemically by assessing microglial activation in the spinal cord with anti-OX-42 and phosphorylated p38 mitogen-activated protein kinase antibodies. Implantation of ketoprofen-infiltrated gelatin hydrogel exerted a sustained analgesic effect for 1 week after the operation. Preemptive analgesia with zaltoprofen, another NSAID, produced an additive analgesic effect in conjunction with the ketoprofen-infiltrated hydrogel. Microglial activation was attenuated by the treatment with ketoprofen-infiltrated hydrogel on day 3 after the incision. These results demonstrate that ketoprofen was effective in reducing mechanical hypersensitivity for 1 week in a rat model of postoperative pain and that the implantation of NSAID-infiltrated gelatin hydrogel may serve as a useful analgesic method for the long-term relief of patients after surgery.

Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels

The generation of functional, 3D vascular networks is a fundamental prerequisite for the development of many future tissue engineering-based therapies. Current approaches in vascular network bioengineering are largely carried out using natural hydrogels as embedding scaffolds. However, most natural hydrogels present a poor mechanical stability and a suboptimal durability, which are critical limitations that hamper their widespread applicability. The search for improved hydrogels has become a priority in tissue engineering research. Here, the suitability of a photopolymerizable gelatin methacrylate (GelMA) hydrogel to support human progenitor cell-based formation of vascular networks is demonstrated. Using GelMA as the embedding scaffold, it is shown that 3D constructs containing human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSCs) generate extensive capillary-like networks in vitro. These vascular structures contain distinct lumens that are formed by the fusion of ECFC intracellular vacuoles in a process of vascular morphogenesis. The process of vascular network formation is dependent on the presence of MSCs, which differentiate into perivascular cells occupying abluminal positions within the network. Importantly, it is shown that implantation of cell-laden GelMA hydrogels into immunodeficient mice results in a rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, it is shown that the degree of methacrylation of the GelMA can be used to modulate the cellular behavior and the extent of vascular network formation both in vitro and in vivo. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

Intrascleral outflow after deep sclerectomy with absorbable and non-absorbable implants in the rabbit eye

SummaryBackgroundThe purpose of the study is an analysis of intrascleral drainage vessels formed in rabbits’ eyes after non-penetrating deep sclerectomy (NPDS) with absorbable and non-absorbable implants, and comparison to eyes in which surgery was performed without implanted material.Material/MethodsNPDS was carried out in 12 rabbits, with implantation of non-absorbable methacrylic hydrogel (N=10 eyes) or absorbable cross-linked sodium hyaluronate (N=6 eyes), or without any implant (N=8 eyes). All the animals were euthanized 1 year after surgery. Twenty-one eyeballs were prepared for light microscopy and 3 were prepared for transmission electron microscope (TEM) analysis. Aqueous humour pathways were stained with ferritin in 6 eyeballs.ResultsBy light microscopy, small vessels adjacent to the areas of scarring were the most common abnormality. Vessel density was significantly higher in operated sclera compared to normal, healthy tissue, regardless of the type of implant used. The average vessel densities were 2.18±1.48 vessels/mm2 in non-implanted sclera, 2.34±1.69 vessels/mm2 in eyes with absorbable implants, and 3.64±1.78 vessels/mm2 in eyes with non-absorbable implants. Analysis of iron distribution in ferritin-injected eyes showed a positive reaction inside new aqueous draining vessels in all groups. TEM analysis showed that the ultrastructure of new vessels matched the features of the small veins.ConclusionsAqueous outflow after NPDS can be achieved through the newly formed network of small intrascleral veins. Use of non-absorbable implants significantly increases vessel density in the sclera adjacent to implanted material compared to eyes in which absorbable implants or no implants were used.

Abstract P175: Selective Regional Injections of Alginate Hydrogel into Cardiac Veins Improve Left Ventricular Function and Reverse Chamber Remodeling in Dogs with Chronic Heart Failure

Background: Progressive LV enlargement and dysfunction are characteristics of heart failure (HF) and are associated with increased mortality and morbidity. We tested the hypothesis that selective regional injections of alginate hydrogel implants (AHI, Algisyl-LVR, Lonestar Heart, Inc.) into isolated segments of epicardial veins of the failing LV will increase LV wall thickness and lead to reduced LV size, lower LV wall stress and improved LV systolic and diastolic function. Methods: 12 dogs with coronary microembolization-induced HF (LV ejection fraction, EF&lt;30%) were studied. During an open-chest procedure, 1.5 to 2.0 cm segments of the 2 nd diagonal branch and the 2 nd marginal branch of the cardiac epicardial veins were isolated by ligation with silk sutures. In 6 dogs, the isolated segments were each injected with 1.0 ml of AHI and in 6 dogs with normal saline (controls). LV ED volume (EDV), ES volume (ESV), EF, stroke volume (SV), ED wall stress (EDWS), deceleration time of early mitral inflow velocity (DT), and severity of functional mitral regurgitation (MR) were measured before therapy (Pre) and at 6 months after AHI or saline delivery (Post). The treatment effect (Δ) was calculated as the difference between Pre and Post. Results: In preliminary we showed that an intravenous injection of 1.0 ml AHI increased regional LV end-diastolic (ED) and end-systolic (ES) wall thickness by 5.8 ± 0.7 % and 9.0 ± 1.0 %, respectively. Compared to saline controls, treatment of HF dogs with AHI prevented the increase in EDV and significantly decreased ESV, EDWS and severity of functional MR (Table). In addition, AHI significantly increased LV EF, SV and DT indicating improved LV systolic and diastolic function (Table). Treatment with Alginate implants also showed a safe and non-arrhythmogenic chronic profile. Conclusion: LV reconstruction using selective regional injections of AHI into epicardial cardiac veins represents a safe novel approach for the treatment of advanced chronic HF. Table 1. Hemodynamic and Ventriculographic Results Control (n=6) AHI (n=6) P-Value ΔEDV (ml) 2.5 ± 1.0 −1.1 ± 0.4 0.114 ΔESV (ml) 4.3 ± 1.7 −3.9 ± 0.4 0.001 ΔEF (%) −3.8 ± 1.5 5.0 ± 0.4 0.001 ΔSV (ml) −1.8 ± 0.8 0.11 ± 0.04 0.001 ΔEDWS (gm/cm²) 9.4 ± 6.5 −23.1 ± 4.6 0.006 ΔDT (msec) −4.7 ± 0.4 27.0 ± 4.4 0.001 ΔMR (%) 1.7 ± 0.8 −3.6 ±1.3 0.004

In vitro– in vivo evaluation of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) hydrogel implants containing cisplatin

The aim of this study was to prepare hydrogel disc implants containing cisplatin from hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA). To control drug release, the monomers were cross-linked with ethyleneglycol dimethacrylate (EGDMA). Implants were characterized by FTIR, DSC and SEM and evaluated for drug content, swelling, tensile strength, in vitro and in vivo drug release, in vitro and in vivo biodegradation of the polymer and histopathological studies. The in vitro results showed that increasing the concentration of either MMA or EGDMA decreased drug release and prolonged the implant life. Histopathological studies showed that the implants were histocompatible with surrounding tissue. Stability studies on the optimized formulation showed it was stable over 90 days at 25±3 °C. The implants can be used to achieve controlled release of drug and attain effective treatment with reduced side effects.

In vitro Studies and Preliminary In vivo Evaluation of Silicified Concentrated Collagen Hydrogels

Hybrid and nanocomposite silica-collagen materials derived from concentrated collagen hydrogels were evaluated in vitro and in vivo to establish their potentialities for biological dressings. Silicification significantly improved the mechanical and thermal stability of the collagen network within the hybrid systems. Nanocomposites were found to favor the metabolic activity of immobilized human dermal fibroblasts while decreasing the hydrogel contraction. Cell adhesion experiments suggested that in vitro cell behavior was dictated by mechanical properties and surface structure of the scaffold. First-to-date in vivo implantation of bulk hydrogels in subcutaneous sites of rats was performed over the vascular inflammatory period. These materials were colonized and vascularized without inducing strong inflammatory response. These data raise reasonable hope for the future application of silica-collagen biomaterials as biological dressings.

Short-term ventricular restraint attenuates post-infarction remodeling in rats

Background/objectivesLeft ventricular restraint attenuates post-infarction remodeling, but may be associated with unfavorable long-term histological response. We hypothesized that beneficial effects can be obtained with short-term restraint during the early post-infarction period; for this purpose, we evaluated a biodegradable scaffold in the in vivo rat model and compared it with epicardial hydrogel application. MethodsA total of 230 Wistar rats (358±7g) were studied. Implantation was performed with and without prior myocardial infarction, induced by permanent coronary artery ligation. Diastolic filling was evaluated by left ventricular pressure recordings after scaffold implantation. Degradation rates and inflammatory/foreign body response were studied at 3, 7 and 15days post-ligation. Remodeling indices were evaluated by echocardiography 15days post-ligation. ResultsNo differences were found in diastolic pressure. Biodegradability was ~50% by 7days and 100% by 15days for both materials. Likewise, inflammatory/foreign body response peaked at 3days post-implant, with subsequent remission, but fibroblastic reaction was more pronounced after scaffold than after hydrogel implantation. Post-ligation, ejection fraction was higher in the scaffold (40.0±1.5%) or hydrogel groups (37.0±1.3%), compared to controls (30.6±1.9%). Wall tension index was lower with either biomaterial, but left ventricular end-diastolic diameter was shorter (p=0.044) and sphericity was attenuated (p=0.029) after scaffold, compared to hydrogel implantation. ConclusionsBoth biomaterials showed a favorable histological response and attenuated remodeling, but epicardial restraint produced better results compared to hydrogel alone. The latter approach merits further investigation due to the ease of implantation.

The Effect of Tissue Wrapping on the Expansion of Hydrophilic Orbital Implants

Hydrogel implants have been used in hypoplastic orbital expansion. Advantages include insertion through a small incision and expansion without manipulation. The rapid rate of expansion, however, may lead to undesirable outcomes, including implant migration. The authors evaluate the effect of tissue wrapping on expansion of hydrogel implants. Three identical hydrogel implants were subjected to one of 3 in vitro interventions: unwrapped control, porcine scleral-wrapped, and porcine fascia-wrapped. Each implant was submerged in normal saline solution. Diameter and volume were measured hourly for 24 hours and then every 4 hours until a plateau or maximal weight was achieved. Measurements were plotted with time as the independent variable and the above measurements as dependent variables. In addition, the best exponential function was graphed and the area under the curve was calculated. Linear plots of data showed a reduction in the rate of diameter and volume expansion for wrapped implants. The areas under the curve of the best-fit exponential function were less for both scleral- and fascia-wrapped implants. Fascia wrapping slowed the rate of volume expansion more than sclera. Also, fascia wrapping seemed to significantly reduce the final implant diameter and volume. Tissue wrapping slows the rate of expansion of hydrogel spheres in vitro. Fascia wrapping may also reduce the final implant size.

High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury

A major hurdle for regeneration after spinal cord injury (SCI) is the ability of axons to penetrate and grow through the scar tissue. After SCI, inflammatory cells, astrocytes and meningeal cells all play a role in developing the glial scar. In addition, degradation of native high molecular weight (MW) hyaluronic acid (HA), a component of the extracellular matrix, has been shown to induce activation and proliferation of astrocytes. However, it is not known if the degradation of native HA actually enhances glial scar formation. We hypothesize that the presence of high MW HA (HA with limited degradation) after SCI will decrease glial scarring. Here, we demonstrate that high MW HA decreases cell proliferation and reduces chondroitin sulfate proteoglycan (CSPG) production in cultured neonatal and adult astrocytes. In addition, stiffness-matched high MW HA hydrogels crosslinked to resist degradation were implanted in a rat model of spinal dorsal hemisection injury. The numbers of immune cells (macrophages and microglia) detected at the lesion site in animals with HA hydrogel implants were significantly reduced at acute time points (one, three and ten days post-injury). Lesioned animals with HA implants also exhibited significantly lower CSPG expression at ten days post-injury. At nine weeks post-injury, animals with HA hydrogel implants exhibited a significantly decreased astrocytic response, but did not have significantly altered CSPG expression. Combined, these data suggest that high MW HA, when stabilized against degradation, mitigates astrocyte activation in vitro and in vivo. The presence of HA implants was also associated with a significant decrease in CSPG deposition at ten days after SCI. Therefore, HA-based hydrogel systems hold great potential for minimizing undesired scarring as part of future repair strategies after SCI.