移植肝细胞与胶原水凝胶单元皮下创建工程化肝组织

背景：胶原水凝胶可为肝细胞生长和组织重建提供良好的基质支持,并且以胶原为基质构建的工程化组织易于合并生长,形成融合组织。目的：尝试将肝细胞/胶原水凝胶复合物打散成小块肝单元,堆积在皮下腔中,提高工程化肝组织厚度。方法：将新鲜分离的大鼠肝细胞与胶原水凝胶复合,构建肝细胞/胶原水凝胶复合物,待固化后将其打散成小块肝单元,以未打散的肝细胞/胶原水凝胶复合物作为对照。取6只SD大鼠,其中3只切除2/3肝脏,诱导肝再生,于双侧腹股沟皮下腔中分别植入打散与未打散的肝细胞/胶原水凝胶复合物;另3只于双侧腹股沟皮下腔中分别植入打散与未打散的肝细胞/胶原水凝胶复合物。植入后7 d取材,采用苏木精-伊红染色、免疫组化染色、印度墨水灌注等方法对工程化肝组织形成情况进行评价。结果与结论：两组移植物均在皮下腔中形成了血管工程化肝组织,但小块肝单元相互融合,形成了大块血管工程化肝组织,肝组织厚度可达4 mm;整块植入的肝移植物只形成小块肝组织,其厚度只有几层细胞。免疫组织化学染色证实,血管工程化肝组织中的肝细胞具有天然肝细胞的特征及功能。肝部分切除实验表明,工程化肝组织具有对肝部分切除再生刺激产生反应的能力。结果表明将肝细胞/胶原水凝胶移植物打散成小块单元,堆积在皮下腔中,可提高工程化肝组织的厚度。  中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Hyaluronic acid-based clinical biomaterials derived for cell and molecule delivery in regenerative medicine

The development of injectable and biocompatible vehicles for delivery, retention, growth, and differentiation of stem cells is of paramount importance for regenerative medicine. For cell therapy and the development of clinical combination products, we created a hyaluronan (HA)-based synthetic extracellular matrix (sECM) that provides highly reproducible, manufacturable, approvable, and affordable biomaterials. The composition of the sECM can be customized for use with progenitor and mature cell populations obtained from skin, fat, liver, heart, muscle, bone, cartilage, nerves, and other tissues. This overview describes the design criteria for “living” HA derivatives, and the many uses of this in situ crosslinkable HA-based sECM hydrogel for three-dimensional (3-D) culture of cells in vitro and translational use in vivo. Recent advances allow rapid expansion and recovery of cells in 3-D, and the bioprinting of engineered tissue constructs. The uses of HA-derived sECMs for cell and molecule delivery in vivo will be reviewed, including applications in cancer biology and tumor imaging.     

Tuning the dependency between stiffness and permeability of a cell encapsulating hydrogel with hydrophilic pendant chains

The mechanical stiffness of a hydrogel plays a significant role in regulating the phenotype of cells that adhere to its surface. However, the effect of hydrogel stiffness on cells cultured within its matrix is not well understood, because of the intrinsic inverse dependency between the permeability and stiffness of hydrogels. This study therefore presents an advanced biomaterial design strategy to decrease the inverse dependency between permeability and stiffness of a cell encapsulating hydrogel. Hydrogels were made by cross-linking poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) monoacrylate (PEGMA), with PEGMA acting as a pendant polymer chain. Increasing the mass fraction of PEGMA while keeping the total polymer concentration constant led to a decrease in the elastic modulus (E) of the hydrogel, but caused a minimal increase in the swelling ratio (Q). The size and hydrophobicity of the end groups of pendant PEG chains further fine tuned the dependency between Q and E of the hydrogel. Pure PEGDA hydrogels with varying molecular weights, which show the same range of E but a much greater range of Q, were used as a control. Fibroblasts encapsulated in PEGDA–PEGMA hydrogels displayed more significant biphasic dependencies of cell viability and vascular endothelial growth factor (VEGF) expression on E than those encapsulated in pure PEGDA hydrogels, which were greatly influenced by Q. Overall, the hydrogel design strategy presented in this study will be highly useful to better regulate the phenotype and ultimately improve the therapeutic efficacy of a wide array of cells used in various biology studies and clinical settings.     

京尼平交联脱细胞纤维环基质/壳聚糖水凝胶与兔纤维环源干细胞的生物相容性

BACKGROUND:To improve the mechanical properties and uncontrollability of degradation of decellularized matrix, we manufactured genipin cross-linked decellularized annulus fibrosus matrix/chitosan hydrogels as annulus fibrosus tissue-engineered scaffold.     

Hydrogel protection: a novel approach to reduce bowel inflammation in experimental gastroschisis

Objective

In gastroschisis there is herniation of the fetal bowel into the amniotic cavity that results in severe intestinal dysfunction. In order to reduce bowel exposure to amniotic fluid we used a hydrogel of N-isopropylacrylamide copolymerized with acrylic acid (P(NIPAAm-co-AAc)) to coat the herniated bowel through the use of a fibrin adhesive (Beriplast^®).

Study design

Gastroschisis was created in fetuses of 31 pregnant Sprague–Dawley rats by evisceration of the bowel through a right paramedian incision in the abdominal wall on day 18.5 of pregnancy. The fetuses were separated in four groups of 12 fetuses: control (C), gastroschisis (G), gastroschisis + fibrin adhesive (GA) and gastroschisis + fibrin adhesive + dry hydrogel (GAH). Animals were harvested at day 21.5 of pregnancy and the hydrogel was removed. Fetuses and bowels were weighed and morphometric analysis was performed. Isoelectric focusing of the amniotic fluid determined its electrical charge. We evaluated the hydrogel swelling ratio (Q) in the amniotic fluid. Histological analysis and scanning electronic microscopy (SEM) of the bowel and hydrogel were performed. Our primary outcome was bowel intactness after hydrogel removal and our secondary outcome was the effectiveness of the hydrogel in protecting the bowel against amniotic fluid and its components. Differences among the groups were tested by the ANOVA and Tukey–Kramer post-test method and the statistical significance accepted was for p values <0.05.

Results

The mass of swollen hydrogel was 34 times the mass of dry hydrogel. Isoelectric focusing of the amniotic fluid showed that most of its proteins are negatively charged as the hydrogel. SEM showed that removal of the hydrogel did not damage bowel serosa. Bowel weight, diameter and wall thickness were similar between groups C and GAH but bowel diameter and wall thickness was significantly reduced in C and GAH compared to G and GA (p < 0.001).

Conclusion

The P(NIPAAm-co-AAc) hydrogel does not harm the bowel and provides a safe effective protection with reduction of bowel damage in gastroschisis.     

Friction studies of hydrogel contact lenses using AFM: non-crosslinked polymers of low friction at the surface

The surface of soft contact lenses made of crosslinked poly(2-hydroxyethyl methacrylate), pHEMA, has been investigated with atomic force microscopy in contact mode. The friction force and adhesive force measurements were able to differentiate the non-crosslinked pHEMA chains from the surface of the crosslinked pHEMA networks. These non-crosslinked pHEMA chains at the surface were anchored to the crosslinked pHEMA network, most likely by entanglement and their surfaces were about 2–4 nm higher than the surrounding surface in a dehydrated state. In saline solution, the surface friction and adhesive force of the contact lens were significantly reduced compared to those measured for the surface-dehydrated contact lens.     

A Water-Based Liquid Embolic: Evaluation of its Safety and Efficacy in a Rabbit Kidney Model

PurposeTo evaluate a novel aqueous-based liquid embolic (Embrace Hydrogel Embolic System, [HES]) that has been developed to embolize hypervascular tumors by filling the tumor vascular bed and solidifying into a hydrogel. HES was evaluated for embolization safety and efficacy relative to microspheres in a preclinical rabbit kidney model.Materials and MethodsA renal embolization model in New Zealand white rabbits was utilized. Twenty-four rabbits underwent unilateral kidney embolization via the main renal artery with either HES or 40-μm microspheres. Twenty-two rabbits survived the procedure and were monitored for 2, 12, 17.5, or 26 weeks before sacrifice. All rabbits underwent a repeat renal angiogram before necropsy. HES was evaluated for nontarget embolization, safety, and embolization effectiveness as measured by recanalization and viability of embolized tissue.ResultsBoth embolization materials were found to be safe, with targeted tissue necrosis and absence of nontarget embolization. Prenecropsy angiograms found vascular recanalization in 0/14 (0%) HES-embolized kidneys and in 3/8 (38%) microsphere-embolized kidneys (P = .036). Viable kidney tissue was observed in 2/14 (14%) kidneys embolized with HES and 5/8 (63%) kidneys embolized with microspheres (P = .052). All kidneys embolized with microspheres that showed vascular recanalization had viable tissue on histological sections. HES was observed in vessels as small as 10 μm in diameter in histological analysis.ConclusionsHES provided deep, durable vascular bed embolization that resulted in less recanalization and, on an average, less viable target tissue compared with 40-μm microspheres. No systemic effects or nontarget tissue embolization was identified.     

Thermal analysis of water in p(HEMA) hydrogels

Hydrogels composed of poly(hydroxyethyl methacrylate) (pHEMA) and water were investigated using differential thermal analysis (DTA) and adiabatic calorimetry (AC). The results show that the crystallization of water in the gels is a very gradual process, leading to the development of a metastable, non-equilibrium state. They are not in agreement with models that assume the actual presence of thermodynamically different classes of water in the gels, based on the abnormal melting behaviour of this water. The results indicate that the internal structure of these gels can be described as that of an elastic solution, in which the water molecules are distributed continuously over all possible orientations to and interactions with the polymer.