Gentamicin Release from Photopolymerized PEG Diacrylate and pHEMA Hydrogel Discs and Their In Vitro Antimicrobial Activities

Hydrogels based on poly(ethylene glycol)-diacrylate (PEG-DA) and 2-hydroxyethyl methacrylate (HEMA) were polymerized with cross-linking agent ethylene glycol diacrylate (EGDMA) under mild photoinitiating conditions. PEG-DA and HEMA concentrations of disks with 1 ± 0.3 mm thickness were 30% and 50% w/w and 40% and 60% w/w, respectively. Gentamicin sulphate was incorporated into the hydrogel during photopolymerization and its release kinetics were tested by spectrophotometric method at 255 nm wavelength in phosphate buffer (pH 7.4) and citrate buffer (pH 2.2). The drug release in citrate buffer was faster compared with to phosphate buffer. The release of drug from 40% HEMA containing hydrogel showed Fickian diffusion mechanisms in phosphate buffer (pH 7.4). Antimicrobial efficiency of the samples was tested by agar diffusion method in two different bacterial cultures (Pseudomonas aeruginosa [ATCC 10145], Staphylococcus aureus [ATCC 25923]). Inhibition zone diameter (mm) surrounding each sample was measured after 24 hr incubation of drug loaded disks onto agar plates at 37°C. Inhibition zone formation also confirms that gentamicin sulphate preserves its antimicrobial activity after subjected to photopolymerization conditions.     

An in situ forming collagen-PEG hydrogel for tissue regeneration

There are limited options for surgeons to repair simple or complex tissue defects due to injury, illness or disease. Consequently, there are few treatments for many serious ailments, including neural-related injuries, myocardial infarction and focal hyaline cartilage defects. Tissue-engineered scaffolds offer great promise for addressing these wide-ranging indications; however, there are many considerations that need to be made when conceptualizing a product. For many applications, an in situ forming scaffold that could completely fill defects with complex geometries, adhere to adjacent tissues and foster cell proliferation would be ideal. Additionally, the scaffold would preferably have tailored mechanical properties similar to native tissues and highly controllable gelation kinetics, and would not require an external trigger, such as ultraviolet light, for gelation. We have developed a unique injectable hydrogel system composed of collagen and multi-armed poly(ethylene glycol) (PEG) that meets all of these criteria. The collagen component enables cellular adhesion and permits enzymatic degradation, while the multi-armed PEG component has amine-reactive chemistry that also binds proteins/tissue and is hydrolytically degradable. We have characterized the mechanical properties, swelling, degradation rates and cytocompatibility of these novel hydrogels. The hydrogels demonstrated tunable mechanics, variable swelling and suitable degradation profiles. Cells adhered and proliferated to near confluence on the hydrogels over 7 days. These data suggest that these collagen and PEG hydrogels exhibit the mechanical, physical and biological properties suitable for use as an injectable tissue scaffold for the treatment of a variety of simple and complex tissue defects.     

A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms,and future perspectives

The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations (LAPFs) with the aim of improving drug pharmacokinetics and therapeutic efficacy. LAPFs have been proven to extend the half-life of therapeutics, as well as to improve patient adherence; consequently, this enhances the outcome of therapy positively. Over past decades, considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings. Here we review the latest advances of LAPFs in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long acting. Existing strategies are classified into manipulation of in vivo clearance and manipulation of drug release from delivery systems, respectively. And the current challenges and prospects of each strategy are discussed. In addition, we also briefly discuss the design principles of LAPFs and provide future perspectives of the rational design of more effective LAPFs for their further clinical translation.     

水凝胶折叠式人工晶状体远期混浊的观察

目的 实验室及临床观察分析超声乳化白内障吸除联合水凝胶折叠式人工晶状体(IOL)植入术后远期发生混浊的原因.方法 对4例(4只眼)超声乳化白内障吸除联合水凝胶折叠式IOL植入术后12.0～96.0个月(平均33.2个月)发生IOL混浊的患者进行临床观察.其中2例(2只眼)患者行IOL置换术,取出的2枚IOL进行钙特异性茜素红染色病理学检查,用扫描电镜观察混浊IOL表面沉淀物的位置和形态,应用能谱分析法检测沉淀物中的元素成分.结果 裂隙灯显微镜下见白色细小颗粒沉积于IOL前表面.电镜扫描可见有层次感、上下交错,如珊瑚样的颗粒附着于IOL表面.茜素红染色见钙结节和非特异性染色的细胞,能谱分析证实颗粒中含钙和磷元素.结论 水凝胶折叠式IOL表面混浊为颗粒状钙和磷化合物沉淀结晶所致,可能与水凝胶IOL材料易于发生钙磷沉积有关,但确切的发生机制还待更进一步研究.     

Materials for engineering vascularized adipose tissue

Loss of adipose tissue can occur due to congenital and acquired lipoatrophies, trauma, tumor resection, and chronic disease. Clinically, it is difficult to regenerate or reconstruct adipose tissue. The extensive microvsacular network present in adipose, and the sensitivity of adipocytes to hypoxia, hinder the success of typical tissue transfer procedures. Materials that promote the formation of vascularized adipose tissue may offer alternatives to current clinical treatment options. A number of synthetic and natural biomaterials common in tissue engineering have been investigated as scaffolds for adipose regeneration. While these materials have shown some promise they do not account for the unique extracellular microenvironment of adipose. Adipose derived hydrogels more closely approximate the physical and chemical microenvironment of adipose tissue, promote preadipocyte differentiation and vessel assembly in vitro, and stimulate vascularized adipose formation in vivo. The combination of these materials with techniques that promote rapid and stable vascularization could lead to new techniques for engineering stable, vascularized adipose tissue for clinical application. In this review we discuss materials used for adipose tissue engineering and strategies for vascularization of these scaffolds.

Clinical Relevance

Materials that promote formation of vascularized adipose tissue have the potential to serve as alternatives or supplements to existing treatment options, for adipose defects or deficiencies resulting from chronic disease, lipoatrophies, trauma, and tumor resection.     

包茎松凝胶质量控制的研究

目的制备包茎松凝胶,完善包茎松凝胶的质量控制方法。方法采用HPLC法同时测定红霉素和倍他米松的含量。色谱柱:Agilent C_(18);流动相:0.025mol·L~(-1) KH_2PO_4-乙腈(70∶30);流速:1.0mL·min~(-1);检测波长:220nm;柱温:35℃;进样量:20μL。结果倍他米松的线性方程为Y=18.564 X-18.68(r=0.999 3),线性范围:8.6~172μg·mL~(-1);红霉素的线性方程为Y=0.112 5 X-9.87(r=0.995 2),线性范围:150.35~3 007μg·mL~(-1)。结论该方法重复性好,方法可行,能有效控制该制剂的质量。     

Polymer-based mesh as supports for multi-layered 3D cell culture and assays

Three-dimensional (3D) culture systems can mimic certain aspects of the cellular microenvironment found in vivo, but generation, analysis and imaging of current model systems for 3D cellular constructs and tissues remain challenging. This work demonstrates a 3D culture system–Cells-in-Gels-in-Mesh (CiGiM)–that uses stacked sheets of polymer-based mesh to support cells embedded in gels to form tissue-like constructs; the stacked sheets can be disassembled by peeling the sheets apart to analyze cultured cells—layer-by-layer—within the construct. The mesh sheets leave openings large enough for light to pass through with minimal scattering, and thus allowing multiple options for analysis—(i) using straightforward analysis by optical light microscopy, (ii) by high-resolution analysis with fluorescence microscopy, or (iii) with a fluorescence gel scanner. The sheets can be patterned into separate zones with paraffin film-based decals, in order to conduct multiple experiments in parallel; the paraffin-based decal films also block lateral diffusion of oxygen effectively. CiGiM simplifies the generation and analysis of 3D culture without compromising throughput, and quality of the data collected: it is especially useful in experiments that require control of oxygen levels, and isolation of adjacent wells in a multi-zone format.     

Topical drug delivery systems: a patent review

Introduction: Topical administration is the favored route for local delivery of therapeutic agents due to its convenience and affordability. The specific challenge of designing a therapeutic system is to achieve an optimal concentration of a certain drug at its site of action for an appropriate duration.

Areas covered: This review summarizes innovations from the past 3 years (2012–2015) in the field of topical drug delivery for the treatment of local infections of the vagina, nose, eye and skin. The review also throws some light on the anatomy and physiology of these organs and their various defensive barriers which affect the delivery of drugs administered topically.

Expert opinion: Topical administration has been gaining attention over the last few years. However, conventional topical drug delivery systems suffer from drawbacks such as poor retention and low bioavailability. The successful formulation of topical delivery products requires the careful manipulation of defensive barriers and selection of a soluble drug carrier. Extensive research is required to develop newer topical drug delivery systems aiming either to improve the efficacy or to reduce side effects compared to current patented systems.     

HPMA copolymers: Origins, early developments, present, and future

The overview covers the discovery of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, initial studies on their synthesis, evaluation of biological properties, and explorations of their potential as carriers of biologically active compounds in general and anticancer drugs in particular. The focus is on the research in the authors' laboratory — the development of macromolecular therapeutics for the treatment of cancer and musculoskeletal diseases. In addition, the evaluation of HPMA (co)polymers as building blocks of modified and new biomaterials is presented: the utilization of semitelechelic poly(HPMA) and HPMA copolymers for the modification of biomaterial and protein surfaces and the design of hybrid block and graft HPMA copolymers that self-assemble into smart hydrogels. Finally, suggestions for the design of second-generation macromolecular therapeutics are portrayed.     

The effect of mesenchymal stem cells delivered via hydrogel-based tissue engineered periosteum on bone allograft healing

Allografts remain the clinical “gold standard” for treatment of critical sized bone defects despite minimal engraftment and ∼60% long-term failure rates. Therefore, the development of strategies to improve allograft healing and integration are necessary. The periosteum and its associated stem cell population, which are lacking in allografts, coordinate autograft healing. Herein we utilized hydrolytically degradable hydrogels to transplant and localize mesenchymal stem cells (MSCs) to allograft surfaces, creating a periosteum mimetic, termed a ‘tissue engineered periosteum’. Our results demonstrated that this tissue engineering approach resulted in increased graft vascularization (∼2.4-fold), endochondral bone formation (∼2.8-fold), and biomechanical strength (1.8-fold), as compared to untreated allografts, over 16 weeks of healing. Despite this enhancement in healing, the process of endochondral ossification was delayed compared to autografts, requiring further modifications for this approach to be clinically acceptable. However, this bottom-up biomaterials approach, the engineered periosteum, can be augmented with alternative cell types, matrix cues, growth factors, and/or other small molecule drugs to expedite the process of ossification.