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1.
Transl Vis Sci Technol ; 13(6): 12, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38888287

ABSTRACT

Purpose: Recombinant human nerve growth factor (rhNGF; cenegermin-bkbj, OXERVATE) is the first and only U.S. Food and Drug Administration-approved treatment for moderate to severe neurotrophic keratopathy. The aim of this study was to determine the feasibility of incorporating a version of rhNGF in a mucoadhesive hydrogel capable of sustained drug release to the ocular surface. Methods: Hydrogels loaded with rhNGF were synthesized by conjugating chitosan with azidobenzoic acid (Az-Ch), adding rhNGF, and exposing the solution to ultraviolet (UV) radiation to induce photocrosslinking. Az-Ch hydrogels were evaluated for physical properties and rhNGF release profiles. Cytocompatbility of Az-Ch was assessed using immortalized human corneal limbal epithelial (HCLE) cells. TF1 erythroleukemic cell proliferation and HCLE cell proliferation and migration were used to assess the bioactivity of rhNGF released from Az-Ch hydrogels. Results: Az-Ch formed hydrogels in <10 seconds of UV exposure and demonstrated high optical transparency (75-85 T%). Az-Ch hydrogels exhibited good cytocompatibility with no demonstratable effect on HCLE cell morphology or viability. rhNGF was released gradually over 24 hours from Az-Ch hydrogels and retained its ability to induce TF1 cell proliferation. No significant difference was observed between rhNGF released from Az-Ch and freshly prepared rhNGF solutions on HCLE cell proliferation or percent wound closure after 12 hours; however, both were significantly better than control (P < 0.01). Conclusions: rhNGF-loaded Az-Ch hydrogels exhibited favorable physical, optical, and drug-release properties, as well as retained drug bioactivity. This drug delivery system has the potential to be further developed for in vivo and translational clinical applications. Translational Relevance: Az-Ch hydrogels may be used to enhance rhNGF therapy in patients with NK.


Subject(s)
Cell Proliferation , Chitosan , Hydrogels , Nerve Growth Factor , Nerve Growth Factor/pharmacology , Nerve Growth Factor/chemistry , Nerve Growth Factor/administration & dosage , Humans , Chitosan/chemistry , Chitosan/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Cell Proliferation/drug effects , Cell Movement/drug effects , Ultraviolet Rays , Cross-Linking Reagents/chemistry , Limbus Corneae/drug effects , Limbus Corneae/cytology , Recombinant Proteins/chemistry , Drug Delivery Systems/methods
2.
Sci Rep ; 14(1): 11727, 2024 05 22.
Article in English | MEDLINE | ID: mdl-38778161

ABSTRACT

The tear fluid is a readily accessible, potential source for biomarkers of disease and could be used to monitor the ocular response to contact lens (CL) wear or ophthalmic pathologies treated by therapeutic CLs. However, the tear fluid remains largely unexplored as a biomarker source for RNA-based molecular analyses. Using a rabbit model, this study sought to determine whether RNA could be collected from commercial CLs and whether the duration of CL wear would impact RNA recovery. The results were referenced to standardized strips of filtered paper (e.g., Shirmer Strips) placed in the inferior fornix. By performing total RNA isolation, precipitation, and amplification with commercial kits and RT-PCR methods, CLs were found to have no significant differences in RNA concentration and purity compared to Schirmer Strips. The study also identified genes that could be used to normalize RNA levels between tear samples. Of the potential control genes or housekeeping genes, GAPDH was the most stable. This study, which to our knowledge has never been done before, provides a methodology for the detection of RNA and gene expression changes from tear fluid that could be used to monitor or study eye diseases.


Subject(s)
Contact Lenses , RNA , Tears , Tears/metabolism , Animals , Rabbits , RNA/isolation & purification , RNA/genetics , RNA/analysis
3.
Pharmaceutics ; 14(12)2022 Dec 08.
Article in English | MEDLINE | ID: mdl-36559244

ABSTRACT

This study aimed to develop a miltefosine-eluting contact lens (MLF-CL) device that would allow sustained and localized miltefosine release for the treatment of Acanthamoeba keratitis. MLF-CLs were produced in three different miltefosine doses by solvent-casting a thin miltefosine-polymer film around the periphery of a methafilcon hydrogel, which was then lathed into a contact lens. During seven days of in vitro testing, all three formulations demonstrated sustained release from the lens at theoretically therapeutic levels. Based on the physicochemical characterization of MLF-CLs, MLF-CL's physical properties are not significantly different from commercial contact lenses in terms of light transmittance, water content and wettability. MLF-CLs possessed a slight reduction in compression modulus that was attributed to the inclusion of polymer-drug films but still remain within the optimal range of soft contact lenses. In cytotoxicity studies, MLF-CL indicated up to 91% viability, which decreased proportionally as miltefosine loading increased. A three-day biocompatibility test on New Zealand White rabbits revealed no impact of MLF-CLs on the corneal tissue. The MLF-CLs provided sustained in vitro release of miltefosine for a week while maintaining comparable physical features to a commercial contact lens. MLF-CL has a promising potential to be used as a successful treatment method for Acanthamoeba keratitis.

4.
Bioengineering (Basel) ; 9(11)2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36354582

ABSTRACT

Chemotherapy is often used to treat retinoblastoma; however, this treatment method has severe systemic adverse effects and inadequate therapeutic effectiveness. Extracellular vesicles (EVs) are important biological information carriers that mediate local and systemic cell-to-cell communication under healthy and pathological settings. These endogenous vesicles have been identified as important drug delivery vehicles for a variety of therapeutic payloads, including doxorubicin (Dox), with significant benefits over traditional techniques. In this work, EVs were employed as natural drug delivery nanoparticles to load Dox for targeted delivery to retinoblastoma human cell lines (Y-79). Two sub-types of EVs were produced from distinct breast cancer cell lines (4T1 and SKBR3) that express a marker that selectively interacts with retinoblastoma cells and were loaded with Dox, utilizing the cells' endogenous loading machinery. In vitro, we observed that delivering Dox with both EVs increased cytotoxicity while dramatically lowering the dosage of the drug. Dox-loaded EVs, on the other hand, inhibited cancer cell growth by activating caspase-3/7. Direct interaction of EV membrane moieties with retinoblastoma cell surface receptors resulted in an effective drug delivery to cancer cells. Our findings emphasize the intriguing potential of EVs as optimum methods for delivering Dox to retinoblastoma.

5.
Int J Mol Sci ; 23(11)2022 May 25.
Article in English | MEDLINE | ID: mdl-35682600

ABSTRACT

Communication between cells and the microenvironment is a complex, yet crucial, element in the development and progression of varied physiological and pathological processes. Accumulating evidence in different disease models highlights roles of extracellular vesicles (EVs), either in modulating cell signaling paracrine mechanism(s) or harnessing their therapeutic moiety. Of interest, the human cornea functions as a refractive and transparent barrier that protects the intraocular elements from the external environment. Corneal trauma at the ocular surface may lead to diminished corneal clarity and detrimental effects on visual acuity. The aberrant activation of corneal stromal cells, which leads to myofibroblast differentiation and a disorganized extracellular matrix is a central biological process that may result in corneal fibrosis/scarring. In recent years, understanding the pathological and therapeutic EV mechanism(s) of action in the context of corneal biology has been a topic of increasing interest. In this review, we describe the clinical relevance of corneal fibrosis/scarring and how corneal stromal cells contribute to wound repair and their generation of the stromal haze. Furthermore, we will delve into EV characterization, their subtypes, and the pathological and therapeutic roles they play in corneal scarring/fibrosis.


Subject(s)
Corneal Diseases , Corneal Injuries , Extracellular Vesicles , Cicatrix/pathology , Cornea/metabolism , Corneal Diseases/etiology , Corneal Diseases/pathology , Corneal Injuries/metabolism , Extracellular Vesicles/metabolism , Fibrosis , Humans , Wound Healing/physiology
6.
J Control Release ; 345: 625-645, 2022 05.
Article in English | MEDLINE | ID: mdl-35321827

ABSTRACT

OBJECTIVE: To perform a bibliometric analysis in the field of ocular drug delivery research to characterize the current international trends and to present visual representations of the past and emerging trends on ocular drug delivery research over the past decade. METHOD: In this cross-sectional study, a bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database was performed to analyze evolution and theme trends on ocular drug delivery research from January 1, 2001, to December 31, 2020. A total of 4334 articles on ocular drug delivery were evaluated for specific characteristics, such as publication year, journals, authors, institutions, countries/regions, references, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed by VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. RESULTS: From 2001 to 2020, the annual global publications increased by 746.15%, from 52 to 440. International Journal of Pharmaceutics published the most manuscripts (250 publications) and produced the highest citations (9509 citations), followed by Investigative Ophthalmology & Visual Science (202 publications) and Journal of Ocular Pharmacology and Therapeutics (136 publications). The United States (1289 publications, 31,512 citations), the University of Florida (82 publications, 2986 citations), and Chauhan, Anuj (52 publications, 2354 citations) were the most productive and impactful institution, country, and author respectively. The co-occurrence cluster analysis of the top 100 keywords form five clusters: (1) micro/nano ocular drug delivery systems; (2) the treatment of inflammation and posterior diseases; (3) macroscopic ocular drug delivery systems/devices; (4) the characteristics of drug delivery systems; (5) and the ocular drug delivery for glaucoma treatment. Diabetic macular edema, anti-VEGF, ranibizumab, bevacizumab, micelles and latanoprost, were the latest high-frequency keywords, indicating the emerging frontiers of ocular drug delivery. Further discussions into the subtopics were provided to assist researchers to determine the range of research topics and plan research direction. CONCLUSIONS: Over the last two decades there has been a progressive increase in the number of publications and citations on research related to ocular drug delivery across many countries, institutions, and authors. The present study sheds light on current trends, global collaboration patterns, basic knowledge, research hotspots, and emerging frontiers of ocular drug delivery. Novel solutions for ocular drug delivery and the treatment of inflammation and posterior diseases were the major themes over the last 20 years.


Subject(s)
Diabetic Retinopathy , Macular Edema , Bibliometrics , Cross-Sectional Studies , Drug Delivery Systems , Humans , Inflammation , United States
7.
Article in English | MEDLINE | ID: mdl-34731742

ABSTRACT

Besifloxacin has been embraced for the treatment of ocular bacterial infections. While LC-MS/MS has been used in investigating BSF pharmacokinetics, those costly instruments are not universally available and have complicated requirements for operation and maintenance. Additionally, pharmacokinetics of besifloxacin in dose-intense regimens are still unknown. Herein, a new quantification method was developed employing the widely accessible HPLC with fluorescence detection and applied to an ocular pharmacokinetic study with an intense regimen. Biosamples were pre-treated using protein precipitation. Chromatographic separation was achieved on a C18 column using mobile phase of 0.1% trifluoroacetic acid and acetonitrile. To address the weak fluorescence issue of besifloxacin, effects of detection parameters, elution pattern, pH of mobile phase, and reconstitution solvents were investigated. The method was fully validated per US-FDA guidelines and demonstrated precision (<13%), accuracy (91-112%), lower limit of quantification (5 ng/mL), linearity over clinically relevant concentrations (R2 > 0.999), matrix-effects (93-105%), recoveries (95-106%), and excellent selectivity. The method showed agreement with agar disk diffusion assays for in vitro screening and comparable in vivo performance to LC-MS/MS (Deming Regression, y = 1.010x + 0.123, r = 0.997; Bland-Altman analysis, mean difference was -6.3%; n = 21). Pharmacokinetic parameters suggested superior surface-retentive properties of besifloxacin. Maximum concentrations were 1412 ± 1910 and 0.15 ± 0.12 µg/mL; area under the curve was 1,637 and 1.08 µg·h/g; and half-life was 4.9 and 4.1 h; and pharmacokinetic-to-pharmacodynamic ratios were ≥ 409 and ≤ 17.8 against ocular pathogens in tears and aqueous humor, respectively. This readily available method is sensitive for biosamples and practical for routine use, facilitating besifloxacin therapy development.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Azepines/chemistry , Azepines/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Fluoroquinolones/chemistry , Fluoroquinolones/pharmacokinetics , Keratitis/drug therapy , Tandem Mass Spectrometry/methods , Animals , Anti-Bacterial Agents/administration & dosage , Aqueous Humor/chemistry , Azepines/administration & dosage , Chromatography, High Pressure Liquid/instrumentation , Female , Fluorescence , Fluoroquinolones/administration & dosage , Humans , Limit of Detection , Male , Rabbits , Tears/chemistry
8.
Cornea ; 40(9): 1175-1180, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34294635

ABSTRACT

PURPOSE: To evaluate the safety and efficacy of an experimental dexamethasone-eluting contact lens (DCL) for the prevention of postphotorefractive keratectomy (PRK) corneal haze in a New Zealand White (NZW) rabbit model. METHODS: Both eyes of 29 NZW rabbits underwent PRK. The rabbits were randomized to one of the 5 study arms for 4 weeks: tarsorrhaphy only, tarsorrhaphy and bandage contact lens (BCL) replaced weekly, tarsorrhaphy and BCL for 1 week plus topical 0.1% dexamethasone ophthalmic solution (drops) for 4 weeks, tarsorrhaphy and BCL replaced weekly plus topical dexamethasone for 4 weeks, and tarsorrhaphy and DCL changed weekly for 4 weeks. Each week for 4 consecutive weeks postoperatively, the tarsorrhaphies were opened, the eyes underwent evaluation and imaging, and the tarsorrhaphies were replaced. Contact lenses were cultured on removal. Central corneal haze was assessed weekly with corneal densitometry. After 4 weeks, the animals were killed, and the eyes were enucleated for histopathologic analysis. RESULTS: The tarsorrhaphy only group displayed more haze with a greater change in optical densitometry from pre-op compared with the other treatment groups. There was no difference between the DCL group and the groups receiving a BCL and dexamethasone drops in densitometry or histopathology. No NZW rabbits developed clinical signs of infection, and cultures from DCLs and BCLs grew similar organisms. CONCLUSIONS: In the post-PRK rabbit model, DCLs worn weekly for 4 weeks were safe and as effective at preventing corneal haze as 0.1% dexamethasone drops applied 4 times a day for 4 weeks.


Subject(s)
Cicatrix/prevention & control , Contact Lenses , Corneal Diseases/prevention & control , Dexamethasone/administration & dosage , Disease Models, Animal , Drug Carriers , Glucocorticoids/administration & dosage , Photorefractive Keratectomy/adverse effects , Postoperative Complications , Animals , Cicatrix/etiology , Corneal Diseases/etiology , Female , Lasers, Excimer , Ophthalmic Solutions , Rabbits
9.
Acta Biomater ; 116: 149-161, 2020 10 15.
Article in English | MEDLINE | ID: mdl-32814140

ABSTRACT

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. STATEMENT OF SIGNIFICANCE: Inflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses.


Subject(s)
Contact Lenses , Uveitis , Animals , Cornea , Humans , Inflammation/drug therapy , Rabbits , Steroids , Uveitis/drug therapy
10.
Biomaterials ; 217: 119285, 2019 10.
Article in English | MEDLINE | ID: mdl-31299627

ABSTRACT

Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug's residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits.


Subject(s)
Contact Lenses , Dexamethasone/administration & dosage , Dexamethasone/pharmacology , Drug Delivery Systems , Administration, Topical , Animals , Cornea/drug effects , Delayed-Action Preparations/pharmacology , Dexamethasone/blood , Dexamethasone/pharmacokinetics , Dose-Response Relationship, Drug , Drug Liberation , Fluorescein Angiography , Humans , Posterior Eye Segment/drug effects , Rabbits , Retina/diagnostic imaging , Retina/drug effects , Vascular Endothelial Growth Factor A
11.
Ophthalmology ; 123(10): 2085-92, 2016 10.
Article in English | MEDLINE | ID: mdl-27586444

ABSTRACT

PURPOSE: To assess the ability of latanoprost-eluting contact lenses to lower the intraocular pressure (IOP) of glaucomatous eyes of cynomolgus monkeys. DESIGN: Preclinical efficacy study of 3 treatment arms in a crossover design. PARTICIPANTS: Female cynomolgus monkeys with glaucoma induced in 1 eye by repeated argon laser trabeculoplasty. METHODS: Latanoprost-eluting low-dose contact lenses (CLLO) and high-dose contact lenses (CLHI) were produced by encapsulating a thin latanoprost-polymer film within the periphery of a methafilcon hydrogel, which was lathed into a contact lens. We assessed the IOP-lowering effect of CLLO, CLHI, or daily latanoprost ophthalmic solution in the same monkeys. Each monkey consecutively received 1 week of continuous-wear CLLO, 3 weeks without treatment, 5 days of latanoprost drops, 3 weeks without treatment, and 1 week of continuous-wear CLHI. On 2 consecutive days before initiation of each study arm, the IOP was measured hourly over 7 consecutive hours to establish the baseline IOP. Two-tailed Student t tests and repeated-measures analysis of variance were used for statistical analysis. MAIN OUTCOME MEASURES: Intraocular pressure. RESULTS: Latanoprost ophthalmic solution resulted in IOP reduction of 5.4±1.0 mmHg on day 3 and peak IOP reduction of 6.6±1.3 mmHg on day 5. The CLLO reduced IOP by 6.3±1.0, 6.7±0.3, and 6.7±0.3 mmHg on days 3, 5, and 8, respectively. The CLHI lowered IOP by 10.5±1.4, 11.1±4.0, and 10.0±2.5 mmHg on days 3, 5, and 8, respectively. For the CLLO and CLHI, the IOP was statistically significantly reduced compared with the untreated baseline at most time points measured. The CLHI demonstrated greater IOP reduction than latanoprost ophthalmic solution on day 3 (P = 0.001) and day 5 (P = 0.015), and at several time points on day 8 (P < 0.05). CONCLUSIONS: Sustained delivery of latanoprost by contact lenses is at least as effective as delivery with daily latanoprost ophthalmic solution. More research is needed to determine the optimal continuous-release dose that would be well tolerated and maximally effective. Contact lens drug delivery may become an option for the treatment of glaucoma and a platform for ocular drug delivery.


Subject(s)
Coated Materials, Biocompatible , Contact Lenses , Glaucoma/therapy , Intraocular Pressure/drug effects , Prostaglandins F, Synthetic/pharmacology , Animals , Anterior Eye Segment/diagnostic imaging , Anterior Eye Segment/drug effects , Antihypertensive Agents/pharmacology , Delayed-Action Preparations , Disease Models, Animal , Dose-Response Relationship, Drug , Equipment Design , Female , Follow-Up Studies , Glaucoma/physiopathology , Latanoprost , Macaca fascicularis , Tomography, Optical Coherence , Tonometry, Ocular
12.
Biomaterials ; 35(1): 432-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24094935

ABSTRACT

For nearly half a century, contact lenses have been proposed as a means of ocular drug delivery, but achieving controlled drug release has been a significant challenge. We have developed a drug-eluting contact lens designed for prolonged delivery of latanoprost for the treatment of glaucoma, the leading cause of irreversible blindness worldwide. Latanoprost-eluting contact lenses were created by encapsulating latanoprost-poly(lactic-co-glycolic acid) films in methafilcon by ultraviolet light polymerization. In vitro and in vivo studies showed an early burst of drug release followed by sustained release for one month. Contact lenses containing thicker drug-polymer films demonstrated released a greater amount of drug after the initial burst. In vivo, single contact lenses were able to achieve, for at least one month, latanoprost concentrations in the aqueous humor that were comparable to those achieved with topical latanoprost solution, the current first-line treatment for glaucoma. The lenses appeared safe in cell culture and animal studies. This contact lens design can potentially be used as a treatment for glaucoma and as a platform for other ocular drug delivery applications.


Subject(s)
Contact Lenses , Drug Delivery Systems , Glaucoma/drug therapy , Prostaglandins F, Synthetic/administration & dosage , Animals , Drug Stability , Intraocular Pressure/drug effects , Latanoprost , Prostaglandins F, Synthetic/pharmacology , Prostaglandins F, Synthetic/therapeutic use , Rabbits
13.
AAPS J ; 14(3): 482-90, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22535508

ABSTRACT

Herein, we report on continued efforts to understand an implantable poly(ethylene glycol) diacrylate (PEGDA) hydrogel drug delivery system that responds to extracellular enzymes, in particular matrix metalloproteinase-2 (MMP-2) to provide controlled drug delivery. By attaching peptide as pendant groups on the hydrogel backbone, drug release occurs at an accelerated rate in the presence of active protease. We investigated MMP-2 entry and optimized parameters of the drug delivery system. Mesh size for different PEGDA molecular weight macromers was measured with PEGDA 3,400 hydrogels having a mesh size smaller than the dimensions of MMP-2 and PEGDA 10,000 and PEGDA 20,000 hydrogels having mesh sizes larger than MMP-2. Purified MMP-2 increased release of peptide fragment compared to buffer at several loading concentrations. Cell-stimulated release was demonstrated using U-87 MG cells embedded in collagen. GM6001, an MMP inhibitor, diminished release and altered the identity of the released peptide fragment. The increase in ratio of release from PEGDA 10,000 and PEGDA 20,000 hydrogels compared to PEGDA 3,400 hydrogels suggests MMP-2 enters the hydrogel. PEGDA molecular weight of 10,000 and 15 % (w/V) were the optimal conditions for release and handling. The use of protease-triggered drug delivery has great advantage particularly with the control of protease penetration as a parameter for controlling rate of release.


Subject(s)
Hydrogels , Matrix Metalloproteinase 2/chemistry , Polyethylene Glycols/chemistry , Cell Line, Tumor , Chromatography, High Pressure Liquid , Humans , Molecular Weight , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
14.
Biomed Mater ; 7(2): 024108, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22455976

ABSTRACT

We recently showed that superporous hydrogel (SPH) scaffolds promote long-term stem cell viability and cell driven mineralization when cells were seeded within the pores of pre-fabricated SPH scaffolds. The possibility of cell encapsulation within the SPH matrix during its fabrication was further explored in this study. The impact of each chemical component used in SPH fabrication and each step of the fabrication process on cell viability was systematically examined. Ammonium persulfate, an initiator, and sodium bicarbonate, the gas-generating compound, were the two components having significant toxicity toward encapsulated cells at the concentrations necessary for SPH fabrication. Cell survival rates were 55.7% ± 19.3% and 88.8% ± 9.4% after 10 min exposure to ammonium persulfate and sodium bicarbonate solutions, respectively. In addition, solution pH change via the addition of sodium bicarbonate had significant toxicity toward encapsulated cells with cell survival of only 50.3% ± 2.5%. Despite toxicity of chemical components and the SPH fabrication method, cells still exhibited significant overall survival rates within SPHs of 81.2% ± 6.8% and 67.0% ± 0.9%, respectively, 48 and 72 h after encapsulation. This method of cell encapsulation holds promise for use in vitro and in vivo as a scaffold material for both hydrogel matrix encapsulation and cell seeding within the pores.


Subject(s)
Cell Culture Techniques/methods , Cell Survival/physiology , Hydrogels/chemistry , Tissue Engineering/methods , Tissue Scaffolds , Animals , Cell Proliferation , Materials Testing , Mice , NIH 3T3 Cells , Porosity
15.
Mil Med ; 174(10): 1113-7, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19891227

ABSTRACT

PURPOSE: To evaluate variables unique to our military population to determine whether we can be better predict functional outcome and return to duty of active duty military soldiers with multiligament knee disruption following arthroscopically assisted reconstruction. MATERIALS AND METHODS: Twenty-four active duty Army personnel who underwent arthroscopically assisted reconstruction of multiple ligament disruption by the same surgeon were enrolled in this study. Postoperatively, a standardized knee joint questionnaire was administered and current vocational and recreational status was evaluated. Demographic data as well as military-specific factors to include rank, military occupation specialty, associated injuries, and retention on active duty were reviewed for these patients to determine their correlation with outcome. RESULTS: Overall, 13 (54%) remained on active duty following surgical reconstruction of their knee. There was a positive correlation between military rank and return to military duty. We were unable to correlate physical job demand to postinjury duty status. The Cincinnati Knee Ligament Rating Scale indicated that most soldiers were able to perform sports at "half speed", with "some limits" in daily living function scores. CONCLUSION: Arthroscopically assisted multiligament knee reconstruction enabled only a slight majority of active duty soldiers to return to duty following reconstruction and rehabilitation of this devastating injury.


Subject(s)
Arthroscopy/methods , Knee Injuries/surgery , Ligaments, Articular/surgery , Military Personnel , Adult , Female , Humans , Ligaments, Articular/injuries , Male , Middle Aged , Recovery of Function , Treatment Outcome
16.
Am J Orthop (Belle Mead NJ) ; 38(5): 249-51, 2009 May.
Article in English | MEDLINE | ID: mdl-19584997

ABSTRACT

We describe a technique of resecting the superomedial border of the scapula for treatment of "snapping scapula." We have performed 5 consecutive open resections with the patient in the beach-chair position, and results have been good. This technique may be of particular benefit in patients who undergo concomitant glenohumeral arthroscopy.


Subject(s)
Orthopedic Procedures/methods , Scapula/surgery , Adult , Chronic Disease , Humans , Male , Posture , Shoulder Pain/etiology , Shoulder Pain/surgery , Young Adult
17.
N Am J Sports Phys Ther ; 4(1): 38-45, 2009 Feb.
Article in English | MEDLINE | ID: mdl-21509119

ABSTRACT

BACKGROUND: Previous studies have shown military physical therapists (PT) to have comparable clinical diagnostic accuracy (CDA) and interobserver agreement to orthopaedic surgeons (OS). However, no studies have examined hip pathology or used intraoperative findings as the reference standard for diagnosis. OBJECTIVE: To compare the CDA of physical examination findings among a PT, an OS, and two surgical orthopaedic residents (ORs) for hip labral tears. METHODS: Thirty-six patients (15 males, 21 females) aged 18-47 (mean + SD, 31.4 + 8.1 years) with 37 symptomatic hips were enrolled in a prospective study and underwent a standardized clinical examination followed by hip arthroscopy. A PT, an OS, and two ORs independently performed history and examinations with the emphasis of diagnosis on the results of six special tests. RESULTS: Thirty-two of 37 individuals (86%) had labral tears to the hip at arthroscopy. Analysis of agreement between clinical diagnosis and intra-operative findings of a labral tear produced a CDA of 85.3% (29/34 correct) for the PT, 84.4% (27/32 correct) for the OS, and 80.0% (24/30 correct) for ORs. No significant difference in CDA occurred in comparing the PT, OS, and ORs. CONCLUSIONS: Using arthroscopy as the reference standard, hip labral tears were clinically suspected with 80-85% accuracy. The clinical diagnostic accuracy of the PT, OS, and ORs was high with no significant difference between examiners. In this study, an experienced PT, an OS, and two ORs demonstrated similarly high diagnostic skills.

18.
J Shoulder Elbow Surg ; 16(4): 413-8, 2007.
Article in English | MEDLINE | ID: mdl-17448696

ABSTRACT

The purpose of this report is to compare outcomes after arthroscopic versus open distal clavicle excision in the treatment of refractory acromioclavicular joint pain. A randomized, prospective clinical trial comparing the 6-month and 1-year outcomes of patients undergoing open distal clavicle excision (group 1) with those undergoing arthroscopic distal clavicle excision (group 2) was carried out. The Modified American Shoulder and Elbow Surgeons form, visual analog scale pain score, Short Form 36, and satisfaction questions were assessed preoperatively and at 6 months and 1 year postoperatively. Seventeen patients were enrolled. There was a trend across all measures for earlier or better outcomes (or both) after arthroscopic over open treatment. The improvement in visual analog scale pain score from preoperatively to 1 year postoperatively was significant for group 2 but not group 1 (P = .006 vs P = .13). Occult intra-articular pathology was detected and treated in 50% of group 2 patients. Arthroscopic and open distal clavicle excisions both provide significant pain reduction at 1 year. Both are effective surgeries for the treatment of refractory acromioclavicular joint pain. The ability to diagnosis and treat subtle concomitant shoulder pathology is a unique advantage of the arthroscopic approach.


Subject(s)
Acromioclavicular Joint , Arthroscopy , Clavicle/surgery , Shoulder Pain/surgery , Adult , Chronic Disease , Female , Humans , Male , Middle Aged , Pain Measurement , Patient Satisfaction , Treatment Outcome
20.
Arthroscopy ; 22(5): 567.e1-3, 2006 May.
Article in English | MEDLINE | ID: mdl-16651171

ABSTRACT

Although hip arthroscopy is a new technique, indications for its use are rapidly expanding. With better utilization and understanding of both radiologic assessment of hip pathology and clinical examination, specific intra-articular derangement is being identified. Longitudinal, peripheral, and intrasubstance anterior hip labral tears can be repaired using anterior paratrochanteric and anterior portals with standard hip arthroscopy equipment. Repair of the torn labrum may help re-establish the anatomic function of the labrum, thereby preventing biomechanical compromise through surgical debridement, which may lead to degenerative changes associated with osteoarthritis. Although long-term results are still unknown, results of short-term follow-up are positive.


Subject(s)
Acetabulum/surgery , Arthroscopy/methods , Hip Joint/surgery , Acetabulum/injuries , Adult , Humans
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