Development of high refractive ZnS/PVP/PDMAA hydrogel nanocomposites for artificial cornea implants

A series of high refractive index (RI) ZnS/PVP/PDMAA hydrogel nanocomposites containing ZnS nanoparticles (NPs) were successfully synthesized via a simple ultraviolet-light-initiated free radical co-polymerization method. The average diameter of the ZnS NPs is ∼3 nm and the NPs are well dispersed and stabilized in the PVP/PDMAA hydrogel matrix up to a high content of 60 wt.% in the hydrogel nanocomposites. The equilibrium water content of ZnS/PVP/PDMAA hydrogel nanocomposites varied from 82.0 to 66.8 wt.%, while the content of mercaptoethanol-capped ZnS NPs correspondingly varied from 30 to 60 wt.%. The resulting nanocomposites are clear and transparent and their RIs were measured to be as high as 1.58–1.70 and 1.38–1.46 in the dry and hydrated states, respectively, which can be tuned by varying the ZnS NPs content. In vitro cytotoxicity assays suggested that the introduction of ZnS NPs added little cytotoxicity to the PVP/PDMAA hydrogel and all the hydrogel nanocomposites exhibited minimal cytotoxicity towards common cells. The hydrogel nanocomposites implanted in rabbit eyes can be well tolerated over 3 weeks. Hence, the high RI ZnS/PVP/PDMAA hydrogel nanocomposites with adjustable RIs developed in this work might potentially be a candidate material for artificial corneal implants.     

Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs

Hydrogels can provide a suitable environment for tissue formation by embedded cells, which makes them suitable for applications in regenerative medicine. However, hydrogels possess only limited mechanical strength, and must therefore be reinforced for applications in load-bearing conditions. In most approaches the reinforcing component and the hydrogel network have poor interactions and the synergetic effect of both materials on the mechanical properties is not effective. Therefore, in the present study, a thermoplastic polymer blend of poly(hydroxymethylglycolide-co-ε-caprolactone)/poly(ε-caprolactone) (pHMGCL/PCL) was functionalized with methacrylate groups (pMHMGCL/PCL) and covalently grafted to gelatin methacrylamide (gelMA) hydrogel through photopolymerization. The grafting resulted in an at least fivefold increase in interface-binding strength between the hydrogel and the thermoplastic polymer material. GelMA constructs were reinforced with three-dimensionally printed pHMGCL/PCL and pMHMGCL/PCL scaffolds and tested in a model for a focal articular cartilage defect. In this model, covalent bonds at the interface of the two materials resulted in constructs with an improved resistance to repeated axial and rotational forces. Moreover, chondrocytes embedded within the constructs were able to form cartilage-specific matrix both in vitro and in vivo. Thus, by grafting the interface of different materials, stronger hybrid cartilage constructs can be engineered.     

A novel injectable,cohesive and toughened Si-HPMC (silanized-hydroxypropyl methylcellulose) composite calcium phosphate cement for bone substitution

This study reports on the incorporation of the self-setting polysaccharide derivative hydrogel (silanized-hydroxypropyl methylcellulose, Si-HPMC) into the formulation of calcium phosphate cements (CPCs) to develop a novel injectable material for bone substitution. The effects of Si-HPMC on the handling properties (injectability, cohesion and setting time) and mechanical properties (Young’s modulus, fracture toughness, flexural and compressive strength) of CPCs were systematically studied. It was found that Si-HPMC could endow composite CPC pastes with an appealing rheological behavior at the early stage of setting, promoting its application in open bone cavities. Moreover, Si-HPMC gave the composite CPC good injectability and cohesion, and reduced the setting time. Si-HPMC increased the porosity of CPCs after hardening, especially the macroporosity as a result of entrapped air bubbles; however, it improved, rather than compromised, the mechanical properties of composite CPCs, which demonstrates a strong toughening and strengthening effect. In view of the above, the Si-HPMC composite CPC may be particularly promising as bone substitute material for clinic application.     

聚乙烯醇水凝胶及其复合物的研究与在人工软骨替代材料上的应用

聚乙烯醇水凝胶是一种具有良好生物相容性和力学性能的高弹性材料。本文介绍了聚乙烯醇水凝胶的成型方法，复合改性技术的研究进展，着重对聚乙烯醇水凝胶作为替代材料在关节软骨损伤修复中的研究现状和存在问题进行了综述，并概述了其应用前景和发展方向。     

BMSCs在功能化自组装多肽水凝胶中定向分化神经细胞研究

目的:探讨骨髓基质干细胞(BMSCs)在功能化自组装多肽水凝胶中定向分化为神经细胞及分化后细胞的功能特征。方法:制备功能化自组装多肽水凝胶,分别将BMSCs接种于RADA16自组装多肽水凝胶(对照组)与功能化自组装多肽水凝胶(实验组)表面,观察细胞迁移情况。用预诱导剂b FGF和EGF及定向诱导剂(SHH+RA)时序诱导,应用Nestin、MAP2、GFAP、Ch AT和VAT染色,比较分化后神经样细胞的形态和功能标志的差异。结果:BMSCs在功能化自组装多肽水凝胶中共培养及诱导剂的特定组合和时序的诱导下增殖分化呈现神经元细胞样改变,MAP2阳性细胞百分率较对照组显著提高(P<0.05),GFAP阳性细胞百分率较对照组显著降低(P<0.05),且功能标志Ch AT和VAT只在实验组表达。结论:BMSCs在功能化自组装多肽水凝胶中能定向诱导分化为具有功能的神经细胞。     

A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

Axonal growth within poly (2-hydroxyethyl methacrylate) sponges infiltrated with Schwann cells and implanted into the lesioned rat optic tract

Porous hydrophilic sponges made from 2-hydroxyethyl methacrylate (HEMA) have a number of possible biomedical applications. We have investigated whether these poly(HEMA) hydrogels, when coated with collagen and infiltrated in vitro with cultured Schwann cells, can be implanted into the lesioned optic tract and act as prosthetic bridges to promote axonal regeneration. Nineteen rats (20–21 days old) were given hydrogel/Schwann cell implants. No obvious toxic effects were seen, either to the transplanted glia or in the adjacent host tissue. Schwann cells survived the implantation technique and were immunopositive for the low affinity nerve growth factor receptor, S100 and laminin. Immunohistochemical studies showed that host non-neuronal cells (astrocytes, oligodendroglia and macrophages) migrated into the implanted hydrogels. Astrocytes were the most frequently observed host cell in the polymer bridges. RT97-positive axons were seen in about two thirds of the implants. The axons were closely associated with transplanted Schwann cells and, in some cases, host glia (astrocytes). Individual axons regrowing within the implanted hydrogels could be traced for up to 900 μm, showing that there was continuity in the network of channels within the polymer scaffold. Axons did not appear to be myelinated by either Schwann cells or by migrated host oligodendroglia. In three rats, anterograde tracing with WGA/HRP failed to demonstrate the presence of retinal axons within the hydrogels. The data indicate that poly(HEMA) hydrogels containing Schwann cells have the potential to provide a stable three-dimensional scaffold which is capable of supporting axonal regeneration in the damaged CNS.     

Effect of enhancers and retarders on percutaneous absorption of flurbiprofen from hydrogels

The effect of enhancers/retarders on the transdermal absorption of flurbiprofen from cellulose hydrogels was studied in vitro. The release rate of flurbiprofen and the viscosity of hydrogel matrices were also examined. The flux of flurbiprofen from cellulose hydrogels approximated that from aqueous buffers, whereas the skin reservoir of flurbiprofen was lower with hydrogels. Incorporation of the cosolvents, propylene glycol (PG) and ethanol, did not significantly increase skin absorption of flurbiprofen. Ethanol even reduced the skin reservoir of the drug. Oleic acid, an unsaturated fatty acid, produced the largest skin reservoir of the drug when incorporated into the hydrogels. D-Limonene, a cyclic monoterpene, showed the greatest ability to enhance the flux of flurbiprofen. However, phospholipids as retarders markedly reduced the skin absorption of flurbiprofen. The mechanisms by which enhancers/retarders govern flurbiprofen permeation were elucidated by in vitro permeation studies using various skin types (enhancers/retarders-pretreated skin, stratum corneum (SC)-stripped skin, and delipidized skin) and histological examination. The results suggest different mechanisms and skin structural modifications caused by different enhancers/retarders.     

pH-and thermo-sensitive pluronic/poly(acrylic acid) in situ hydrogels for sustained release of an anticancer drug

In this study, we developed oral in situ gelling formulations composed of pluronic (Plu) and polyacrylic acid (PAA) for the delivery of an anticancer drug, epirubicin (Epi). We investigated various Plu/PAA/Epi formulations for their physicochemical properties and in vitro permeation and accumulation, as well as for in vivo pharmacokinetic and antitumor efficacy. A scanning electron microscopic (SEM) image of Plu 14%/PAA 0.75%/Epi hydrogel showed a sponge-like structure. This formulation has suitable gelation time, water content, bioadhesive force, structural stability, and a high permeation percentage of Epi, with sustained drug release characteristics for 96?h. This hydrogel was retained at the end of the ileum near the colon of Sprague-Dawley (SD) rats for at least 12?h. An in vivo pharmacokinetic study using SD rats showed that after oral administration in this formulation, Epi had prolonged half-life, greater area under the curve, and higher relative bioavailability than in an oral Epi solution. In vivo tumor growth inhibition of Epi in this formulation was more pronounced compared with oral Epi and intravenous Epi solutions in CT-26 mouse colon adenocarcinoma bearing Balb/c mice. This study highlights the advantages of using oral in situ temperature- and pH-sensitive hydrogels for future cancer therapy.