Determination of Residual Acrylamide in Medical Polyacrylamide Hydrogel by High Performance Liquid Chromatography tandem Mass Spectroscopy

Objective To determine residual acrylamide in medical polyacrylamide hydrogel by high performance liquid chromatography tandem mass spectroscopy （HPLC-MS）. Methods After 13C3 labeled acrylamide was added, the sample was extracted with water and then cleaned up with ExtrelutTM 20. The polyacrylamide hydrogel sample and 20 clinical cases were analyzed by HPLC-MS/MS and isotope dilution quantifying technique in selected reaction monitoring （SRM） mode. Results Acrylamide was separated from polyacrylamide hydrogel. The concentration of acrylamide in polyacrylamide hydrogel ranged from 3.9×10^-9 to 3.1×10^- 8g/L in the 20 clinical cases. The peak area was favorable linear and the range was up to 3 000 μg/L. The recovery rate was 103.1% with a relative standard deviation （RSD） of 6.20%, when the mark level was 50 lag/L. Conelusion HPLC-MS is a rapid, accurate, and sensitive method for the determination of residual acrylamide in medical polyacrylamide hydrogel.

ADDITIVE-INDUCED ENHANCEMENT OF OPTICAL CLARITY OF POLYACRYLAMIDE HYDROGEL

The aqueous polymerization of acrylamide and crosslinking with N,N-methylenebisacrylamide afforded hydrogelsdisplaying high levels of light scattering (poor optical clarity). Enhancement of the optical clarity within a polyacrylamide(PAm) hydrogel was accomplished through the implementation of 'refractive index matching'. Water-soluble additives wereutilised to better match the refractive index inhomogeneities throughout a given hydrogel. This resulted in lower lightscattering within the system and hence improved clarity. Amino acids, sugars, polymers, and other water-soluble additivessuch as glycerol were investigated by this methodology. Most additives investigaed displayed potential for effectivelyreducing the light scattering within a PAm hydrogel as a function of increased additive concentration. On increasing therefractive index of the water medium, the overall refractive index of a PAm hydrogel was also observed to increase. Thisprovided a quantitative means of determining the effectiveness of a given additive for improving the optical clarity within ahydrogel.

A review of complications of polyacrylamide hydrogel injection

Once a popular injectable filler,polyacrylamide hydrogel(PAAG)has been banned in China since 2006 due to its unclear safety and long-term complications.However,it is still being used worldwide because of its huge commercial profit,leading to emerging complications and an urgent need for standardized clinical management.This review aimed to assess the properties,safety,and complications of PAAG and treatment strategies for its removal.

A pH-sensitive Modified Polyacrylamide Hydrogel

A pH-sensitive modified polyacrylamide hydrogel was prepared by two steps and the modified polyacrylamide was characterized by ^1HNMR spectrum. The surface morphology and swelling behavior of the hydrogels were investigated.

Swelling Behavior of Polyacrylamide Hydrogels near Phase Transition

Hydrogels based on acrylamide (AA) and sodium methacrylate (NMA) as ionic monomer were prepared by solution polymerization using N,N’-methylenebis(acrylamide) (MBA) or ethylene glycol dimethacrylate (EGMA) as crosslinkers and Ammonium Persulfate (APS) and N,N,N’,N’-Te-tramethyl-ethylenediamine (TMEDA) as initiators. Swelling behavior was greatly affected by NMA content near phase transition. Increasing ionic monomer concentration compared to total monomer one led to high expansion in water, oscillating around 285 g/g for MBA and 325 g/g for EGMA crosslinker, above 20% of NMA. Dynamic Light Scattering experiments were performed and, for both crosslinkers, the dynamic correlation length (ξ) decreased with increasing NMA content, contributing to diminish hydrogels spatial inhomogeneities.

SWELLING EQUILIBRIUM OF NONIONIC POLYACRYLAMIDE HYDROGEL IN AQUEOUS SALT SOLUTIONS

A series of nonionic polyacrylamide hydrogels, using acrylamide as monomer and N,N＇-methylene diacrylamide as crosslinking agent, were prepared by the free radical polymerization in aqueous solution. Swelling equilibria for the gels were carried out in aqueous solutions of NaCl, KCI, CaCl2, Na2HPO4 and K2HPO4 with concentration ranging from 10^-3 to 5mol/kgH2O at 25 ℃. Experimental results revealed that the chlorides and phosphates cause a different behavior at higher salt concentration. The swelling ratio increases with increasing concentration of chlorides salts, while decreases with the increased phosphates salt concentration. The phenomena seem to be related to the different interactions of chloride and hydrogen phosphate ions with the network groups. Furthermore, the effects of different concentration of crosslinking agent and total monomers on gel swelling performance were also investigated.

Tough Semi-interpenetrating Polyvinylpyrrolidone/Polyacrylamide Hydrogels Enabled by Bioinspired Hydrogen-bonding Induced Phase Separation

Semi-interpenetrating(semi-IPN)hydrogels formed by the continuous interpenetration of cross-linked polymer network and linear non-crosslinked polymer with multifunctionality are widely used in biomedical and other fields.However,the negative impact of linear polymer on the homogeneity of the cross-linked network often leads to a decrease in the mechanical properties of semi-IPN hydrogels and severely limits their applications.Herein,a bioinspired hydrogen-bonding induced phase separation strategy is presented to construct the tough semi-IPN polyvinylpyrrolidone/polyacrylamide hydrogels(named PVP/PAM hydrogels),including the linear polymer polyvinylpyrrolidone(PVP)and cross-linked polyacrylamide(PAM)network.The resultant PVPx/PAM hydrogels exhibit unique phase separation induced by the hydrogen bonding between PVP and PAM and affected by the amount of substance of PVP.Meanwhile,the phase separation of PVPx/PAM hydrogels results in excellent mechanical properties with a strain of 2590%,tensile strength of 0.28 MPa and toughness of 2.17 MJ/m^(3).More importantly,the hydrogen bonding between PVP and PAM firstly disrupts to dissipate energy under external forces,so the PVPx/PAM hydrogels exhibit good self-recovery properties and outperform chemically cross-linked PAM hydrogels in impact resistance and damping applications.It is believed that the PVPx/PAM hydrogels with hydrogen-bonding induced phase separation possess more potential application prospects.

Practical strategy to construct anti-osteosarcoma bone substitutes by loading cisplatin into 3D-printed titanium alloy implants using a thermosensitive hydrogel

Surgical resection and perioperative adjuvant chemotherapy-based therapies have improved the prognosis of patients with osteosarcoma;however,intraoperative bone defects,local tumour recurrence,and chemotherapy-induced adverse effects still affect the quality of life of patients.Emerging 3D-printed titanium alloy(Ti6Al4V)implants have advantages over traditional implants in bone repair,including lower elastic modulus,lower stiffness,better bone conduction,more bone in-growth,stronger mechanical interlocking,and lager drug-loading capacity by their inherent porous structure.Here,cisplatin,a clinical first-line anti-osteosarcoma drug,was loaded into Ti6Al4V implants,within a PLGA-PEG-PLGA thermo-sensitive hydrogel,to construct bone substitutes with both anti-osteosarcoma and bone-repair functions.The optimal concentrations of cisplatin(0.8 and 1.6 mg/mL)were first determined in vitro.Thereafter,the anti-tumour effect and biosafety of the cisplatin/hydrogel-loaded implants,as well as their bone-repair potential were evaluated in vivo in tumour-bearing mouse,and bone defect rabbit models,respectively.The loading of cisplatin reduced tumour volume by more than two-thirds(from 641.1 to 201.4 mm3)with negligible organ damage,achieving better anti-tumour effects while avoiding the adverse effects of systemic cisplatin delivery.Although bone repair was hindered by cisplatin loading at 4 weeks,no difference was observed at 8 weeks in the context of implants with versus without cisplatin,indicating acceptable long-term stability of all implants(with 8.48%-10.04%bone in-growth and 16.94%-20.53%osseointegration).Overall,cisplatin/hydrogel-loaded 3D-printed Ti6Al4V implants are safe and effective for treating osteosarcoma-caused bone defects,and should be considered for clinical use.

Self-healing carrageenan-driven polyacrylamide hydrogels for strain sensing

Conductive hydrogels have attached considerable attention due to their good stretchability,excellent conductivity when they are applied in soft electronics. However,to fabricate a flexible hydrogel sensor with excellent toughness and good self-healing properties remains a challenge. In this work,we assembled a dual physical-crosslinking(DPC) ionic conductive polyacrylamide/carrageenan double-network(DN) hydrogel. This hydrogel has excellent fracture tensile stress and toughness,and demonstrates rapid self-recovery and self-healing ability due to the unique dual physical-crosslinking structures. Besides,the hydrogel is highly conductive by adding some conductive ions. As a result,the hydrogel-based sensor can stably detect human motions and physiological signals. The work provides novel ideas for the development of flexible sensing devices.

Fabrication of Core-Shell Hydrogel Bead Based on Sodium Alginate and Chitosan for Methylene Blue Adsorption

A novel core-shell hydrogel bead was fabricated for effective removal of methylene blue dye from aqueous solutions.The core,made of sodium alginate-g-polyacrylamide and attapulgite nanofibers,was cross-linked by Calcium ions(Ca^(2+)).The shell,composed of a chitosan/activated carbon mixture,was then coated onto the core.Fourier transform infrared spectroscopy confirmed the grafting polymerization of acrylamide onto sodium alginate.Scanning electron microscopy images showed the core-shell structure.The core exhibited a high water uptake ratio,facilitating the diffusion of methylene blue into the core.During the diffusion process,the methylene blue was first adsorbed by the shell and then further adsorbed by the core.Adsorption tests showed that the coreshell structure had a larger adsorption capacity than the core alone.The shell effectively enhanced the adsorption capacity to methylene blue compared to the single core.Methylene blue was adsorbed by activated carbon and chitosan in the shell,and the residual methylene blue diffused into the core and was further adsorbed.

阿仑膦酸钠/壳聚糖/聚乙烯醇复合水凝胶膜的制备与表征

背景:骨质疏松症是牙种植治疗的高风险因素,制备缓释阿仑膦酸钠的组织工程支架应用于骨质疏松患者口腔种植手术是当前口腔骨组织工程研究热点。目的:制备阿仑膦酸钠/壳聚糖/聚乙烯醇复合水凝胶膜,表征其缓释性能。方法:(1)采用物理交联法制备不同质量比(壳聚糖与聚乙烯醇的质量比分别为3∶7、5∶5、7∶3)的壳聚糖/聚乙烯醇复合水凝胶膜与单纯的壳聚糖、聚乙烯醇水凝胶膜,通过表征水凝胶膜的形貌、水接触角、力学性能、溶胀率与细胞相容性筛选适宜的水凝胶膜作为阿仑膦酸钠的载体。(2)制备含0,0.4,1.2,2.0 mg/L阿仑膦酸钠的单纯壳聚糖/聚乙烯醇复合水凝胶膜,将大鼠骨髓间充质干细胞分别与4组水凝胶膜共培养,通过CCK-8法与CD44免疫荧光染色检测水凝胶膜的细胞相容性。将载药壳聚糖/聚乙烯醇复合水凝胶膜浸泡于PBS中,采用紫外可见分光光度法检测复合水凝胶膜的药物释放性能。结果与结论:(1)表征结果显示,随着水凝胶膜中聚乙烯醇质量的增加,水凝胶膜的结构密度增加、孔隙率减少,水接触角(均在90°以内)、断裂伸长率与抗压强度增大,平衡溶胀率降低,对大鼠骨髓间充质干细胞的增殖均无影响,单纯壳聚糖水凝胶膜可促进大鼠骨髓间充质干细胞的黏附,3∶7、5∶5比例复合水凝胶膜不影响大鼠骨髓间充质干细胞的黏附,单纯聚乙烯醇水凝胶膜、7∶3比例复合水凝胶膜抑制大鼠骨髓间充质干细胞的黏附,综合以上结果,选择5∶5复合水凝胶膜作为阿仑膦酸钠的载体。(2)CCK-8检测结果显示,含0.4,1.2 mg/L阿仑膦酸钠组复合水凝胶膜无细胞毒性;CD44免疫荧光染色结果显示,含0.4 mg/L阿仑膦酸钠组复合水凝胶膜不影响大鼠骨髓间充质干细胞的黏附,含1.2,2.0 mg/L阿仑膦酸钠组复合水凝胶膜抑制大鼠骨髓间充质干细胞的黏附;含0.4,1.2,2.0 mg/L阿仑膦酸钠的壳聚糖/聚乙烯醇复合水凝胶膜在最初6 h内爆发性释放阿仑膦酸钠,此后均匀稳定地释放阿仑膦酸钠,释放时间达96 h以上。(3)结果表明,5∶5比例的壳聚糖/聚乙烯醇复合水凝胶膜具有良好的理化性能、细胞相容性,可以作为阿仑膦酸钠的缓释载体。

Polyacrylamide gel migration after injection for breast augmentation:A case report

Polyacrylamide hydrogel(PAAG)was once considered a safe,reliable,and compatible injected filler and was widely used in breast augmentation,rhinoplasty,and other cosmetic surgeries.However,numerous complications,such as implant migration,have been observed after PAAG injections.Herein,we report a rare case of distant implant migration after PAAG injection for breast augmentation in which the material became displaced along the abdominal wall to the perineum and pelvic extraperitoneal space.After a well-prepared preoperative evaluation involving magnetic resonance imaging(MRI)and computed tomography(CT)examinations and threedimensional hologram,debridement surgery was performed to remove the injected material.After the operation,the patient was followed up for two years and was not scheduled for a second operation.Postoperative complications of breast augmentation after PAAG injection,especially gel migration,still affect thousands of patients.Once material migration occurs,surgical removal becomes difficult.Early diagnosis and treatment are recommended.

A double-network hydrogel for the dynamic compression of the lumbar nerve root

Current animal models of nerve root compression due to lumbar disc herniation only assess the mechanical compression of nerve roots and the inflammatory response. Moreover, the pressure applied in these models is static, meaning that the nerve root cannot be dynamically compressed. This is very different from the pathogenesis of lumbar disc herniation. In this study, a chitosan/polyacrylamide double-network hydrogel was prepared by a simple two-step method. The swelling ratio of the double-network hydrogel increased with prolonged time, reaching 140. The compressive strength and compressive modulus of the hydrogel reached 53.6 and 0.34 MPa, respectively. Scanning electron microscopy revealed the hydrogel's crosslinked structure with many interconnecting pores. An MTT assay demonstrated that the number of viable cells in contact with the hydrogel extracts did not significantly change relative to the control surface. Thus, the hydrogel had good biocompatibility. Finally, the double-network hydrogel was used to compress the L4 nerve root of male sand rats to simulate lumbar disc herniation nerve root compression. The hydrogel remained in its original position after compression, and swelled with increasing time. Edema appeared around the nerve root and disappeared 3 weeks after operation. This chitosan/polyacrylamide double-network hydrogel has potential as a new implant material for animal models of lumbar nerve root compression. All animal experiments were approved by the Animal Ethics Committee of Neurosurgical Institute of Beijing, Capital Medical University, China(approval No. 201601006) on July 29, 2016.

Interpenetrated Chitosan-Poly(Acrylic Acid-Co-Acrylamide) Hydrogels. Synthesis, Characterization and Sustained Protein Release Studies

Interpenetrated polymer networks of chitosan (CHI), polyacrylic acid (PAA) and polyacrylamide (PAM) were prepared by free radical polymerization. These hydrogels were either washed with double distilled water (CHI/PAA/PAM) A or hydrolyzed with 1M sodium hydroxide (NaOH), (CHI/PAA/PAM) S. Both types of hydrogels were characterized by infrared spectroscopy, microstructural techniques and compressive mechanical testing. Finally, hydrogels were loaded with bovine serum albumin (BSA) and release followed at different pHs. Infrared spectra analysis showed correspondence between hydrogels and monomer feed compositions. Hydrolyzed hydrogels, had increased water content and pH swelling dependence. Compression modulus of swelled hydrolyzed hydrogels decreased with increasing equilibrium water content. Higher BSA loadings were achieved on hydrolyzed hydrogels due to their high water content and porosity. Protein release from hydrogels was low (≤ 20% after 10 hours) at pH 1.2, but sustained release was observed at pH 6.8 and 7.4. The integrity of the protein released at 6.8 and 7.4 by hydrolyzed hydrogels was unaffected. The hydrogles showed no cytotoxic effects on human skin dermal fibroblasts as determined by MTT assay except for two compositions of (CHI/PAA/PAM) A samples, which after seven days presented a viability lower than 80% respect to the control.

氧化κ-卡拉胶/聚丙稀酰胺水凝胶的制备与表征

为提高κ-卡拉胶水凝胶的应用性能,该文以κ-卡拉胶(κ-carrageenan, KC)为原料,通过TEMPO/NaClO/NaBr(TEMPO:2,2,6,6-四甲基哌啶-1-氧基自由基,2,2,6,6-tetramethylpiperidoxyl)反应体系制备氧化κ-卡拉胶(oxidizedκ-carrageenan, OKC),再用OKC与聚丙烯酰胺(polyacrylamide, PAM)以不同质量比进行复配,采用化学交联法制备了氧化κ-卡拉胶/聚丙烯酰胺水凝胶,通过测定水凝胶的含水率、水溶性、溶胀率、机械性能、红外光谱和微观结构,探究了氧化κ-卡拉胶对水凝胶应用性能的影响。结果表明,OKC可显著提高复合水凝胶的溶胀率、拉伸强度和断裂伸长率、降低水溶性(P<0.05),且当OKC与AM质量比为3∶4时,复合水凝胶的性能指标达最优值,即OKC3/PAM4含水率为82.7%,水溶性为12.2%,溶胀率为887%,拉伸强度达0.223 MPa,断裂伸长率达448%;红外光谱分析显示,κ-卡拉胶中的C-6醇羟基成功氧化为C-6羧基,氧化κ-卡拉胶/聚丙烯酰胺水凝胶各组分之间存在氢键;扫描电镜显示,OKC/PAM水凝胶具有致密多孔的三维网状结构,孔径均匀、规整。因此,氧化κ-卡拉胶与聚丙烯酰胺复配可制备成性能良好的水凝胶,将为开发卡拉胶水凝胶医用敷料提供理论基础。

负载外泌体的可注射水凝胶修复种植体周围骨缺损

背景:大量的研究已证实,外泌体具有促进成骨与血管化的作用,但是单纯的外泌体治疗存在靶向性差、负载分子含量无法达到治疗浓度等问题。目的:将外泌体负载于可注射葡萄糖酸内酯-海藻酸钠/β-磷酸三钙-聚乙二醇水凝胶中,通过体内与体外实验观察该水凝胶在种植体周围骨缺损中的作用。方法:从骨髓间充质干细胞中提取外泌体,并将其包裹于可注射葡萄糖酸内酯-海藻酸钠/β-磷酸三钙-聚乙二醇水凝胶中。①体外实验:将负载与未负载外泌体的水凝胶分别与内皮祖细胞共培养,进行外泌体摄取实验、小管形成实验以及细胞增殖、迁移能力、成血管基因检测。②体内实验:选取雄性新西兰大白兔12只,在一侧股骨长轴制备2个标准种植体窝洞及对应的骨缺损,在近心端的窝洞内植入种植体后,在骨缺损部位植入负载外泌体的水凝胶(实验组);在远心端的种植窝洞内植入种植体后,在骨缺损部位植入未负载外泌体的水凝胶(对照组),术后3,6,9周取带种植体的骨缺损部位,进行苏木精-伊红、Masson染色,同时,术后9周时进行成骨基因与成血管基因检测。结果与结论:①体外实验:外泌体可进入内皮祖细胞中,负载外泌体水凝胶组内皮祖细胞的增殖能力、迁移能力、成血管能力及成血管基因(CD31、血管内皮生长因子及碱性成纤维细胞生长因子)表达均高于未未负载外泌体水凝胶组(P<0.05)。②体内实验:苏木精-伊红、Masson染色显示,术后3周时,两组仅见少量新生骨,材料部分降解;术后6周时,两组新生骨量增加,其中实验组可见大量的新生骨,钙盐沉积明显;术后9周时,相较于对照组,实验组可见大量粗大于成熟的骨小梁,钙盐沉积更加明显,骨小梁周围可见大量排列的成骨细胞。实验组术后9周骨缺损部位的CD31、血管内生长因子、碱性成纤维细胞生长因子、骨形态发生蛋白2、Ⅰ型胶原及骨钙素的蛋白表达均高于对照组(P<0.05)。③负载外泌体的萄糖酸内酯-海藻酸钠/β-磷酸三钙-聚乙二醇水凝胶可促进内皮祖细胞的增殖、迁移与成血管分化,促进种植体周围骨缺损的修复再生。

海藻酸钠/聚丙烯酰胺复合水凝胶的壳聚糖增韧

以天然多糖海藻酸钠(SA)、丙烯酰胺(AM)单体为基础原料构筑双网络水凝胶,引入不同含量的壳聚糖(CS),增强水凝胶的力学韧性。通过扫描电子显微镜、红外光谱、X射线衍射仪及热失重分析仪等表征水凝胶的形貌特征、网络交联结构及热学性能,分析SA/聚丙烯酰胺(PAM)水凝胶的交联机理。结果表明,水凝胶的韧性随CS含量的增加而增加,CS低含量时韧性增加由伸长能力增加引起,而高添加时则因强度伸长同步增加引起,添加10%CS的水凝胶其韧性值达到2.50×10~5 kJ/m~3,明显高于添加5%和7.5%CS的水凝胶;对水凝胶定伸长循环拉伸,其弹性回复率随所定伸长率的增加而有所降低,在25%定伸长时均高于98%,而在200%时只高于90%,其中添加10%CS的水凝胶弹性最佳,且有较强的断裂应力(0.249 MPa)和断裂伸长率(1 635.65%),在200%及以内定伸长循环拉伸时具有优异的回复能力。

Recent advances and innovations in the design and fabrication of wearable flexible biosensors and human health monitoring systems based on conjugated polymers

Wearable biosensors have received great interest as patient-friendly diagnostic technologies because of their high flexibility and conformability.The growing research and utilization of novel materials in designing wearable biosensors have accelerated the development of point-of-care sensing platforms and implantable biomedical devices in human health care.Among numerous potential materials,conjugated polymers(CPs)are emerging as ideal choices for constructing high-performance wearable biosensors because of their outstanding conductive and mechanical properties.Recently,CPs have been extensively incorporated into various wearable biosensors to monitor a range of target biomolecules.However,fabricating highly reliable CP-based wearable biosensors for practical applications remains a significant challenge,necessitating novel developmental strategies for enhancing the viability of such biosensors.Accordingly,this review aims to provide consolidated scientific evidence by summarizing and evaluating recent studies focused on designing and fabricating CP-based wearable biosensors,thereby facilitating future research.Emphasizing the superior properties and benefits of CPs,this review aims to clarify their potential applicability within this field.Furthermore,the fundamentals and main components of CP-based wearable biosensors and their sensing mechanisms are discussed in detail.The recent advancements in CP nanostructures and hybridizations for improved sensing performance,along with recent innovations in next-generation wearable biosensors are highlighted.CPbased wearable biosensors have been—and will continue to be—an ideal platform for developing effective and user-friendly diagnostic technologies for human health monitoring.

P(N-MAAm)水凝胶吸附剂的制备及其对亚甲基蓝染料吸附性能的研究

将N-羟甲基丙烯酰胺引入聚丙烯酸-丙烯酰胺体系,采用“一锅煮”法合成了P(N-MAAm)水凝胶。结果显示,当n(AM)∶n(AA)为1∶4、中和度为60%、交联剂用量为0.4%、n(AM)∶n(N-MA)=9.5∶0.5时,P(N-MAAm)对亚甲基蓝(MB)的实测最大吸附量可达1603.77 mg/g;降低环境温度、盐度,提高pH有利于P(N-MAAm)水凝胶吸附MB;吸附动力学曲线符合准一级动力学模型(R_(1)>0.999),吸附等温线更符合Langmuir模型(R_(L)>0.981),P(N-MAAm)水凝胶对MB的吸附过程更倾向于是物理吸附,并且可能是多分子层吸附。P(N-MAAm)水凝胶通过Langmuir模型拟合计算得到理论最大吸附量为3170.27 mg/g;具有良好的可重复利用性能,5次吸附-解吸循环后对MB的去除率仍高于95%。