Articular cartilage (AC) possesses complex depth-dependent gradients in cell phenotype, matrix composition, metabolism, mechanics, and growth factors. These natural gradients are essential for cartilage function. Because of lack of blood vessels, the repair and treatment of AC defects have been a grand challenge for surgeons, the natural gradients inspired researchers to find solutioninthe gradient construction for AC repair in tissue engineering. This review emphasizes a critical shift from merely describing native gradients to actively implementing gradient-based strategies in scaffold design. Current biomimetic approaches focus on engineering controllable gradients-including cell density, metabolic factors (e.g., oxygen), matrix composition, mechanical properties, and growth factor concentrationswithinthe scaffold. These gradient-enabled constructs can be designed to guide zone-specific cellular responses and extracellular matrix formation, ultimately restoring the native structure and function of AC. We also highlight technologies such as 3D bioprinting, oxygen-releasing biomaterials, perfusion bioreactors, and graded microsphere systems that enable precise spatial control of scaffold properties. A successful gradient-based strategy integrates multiple interdependent gradients rather than relying on a single feature. This review provides a practical framework for developing next-generation biomimetic scaffolds capable of achieving functional AC regeneration for clinical translation.
The practical application of high-temperature proton exchange membranes faces a trade-off between durability and proton transport efficiency. To overcome this challenge, a series of poly [2,2 '-(p-oxidiphenylene)-5,5 ' -benzimidazole] (OPBI)-based crosslinked membranes with tunable triazine content by employing the nitrogenrich triazine-based crosslinker 1,3,5-triazine-2,4,6-triphenylaldehyde (TRIPOD) were fabricated through a onestep thermal crosslinking process in this work. The cross-linking mechanism is investigated using a model compound, which confirms the covalent interaction between the reactive imidazole proton and the aldehyde group of TRIPOD. It is demonstrated that crosslinking strengthens the mechanical properties of the membranes and restricts swelling. Simultaneously, a compact three-dimensional hydrogen bond network is established through robust interactions between the nitrogen-rich triazine core and phosphoric acid (PA). This network further boosts proton transport efficiency and reduces swelling via the effective immobilization of PA. Furthermore, the introduction of the covalent crosslinking network effectively improves the thermal and antioxidant stability of the membranes. Even at a low PA uptake (205.66%), the membrane containing 25 wt% crosslinker (T-OPBI-25) achieves a proton conductivity of 0.1010 S cm- 1 and a single-cell performance of 834.49 mW cm- 2 at 180 degrees C. These values represent 3.73-fold and 3.32-fold improvements over the pristine OPBI membrane (PA uptake: 277.80%) under identical conditions, respectively. Moreover, the voltage decay rate of the T-OPBI-25 membrane is only 0.285 mV h- 1 after continuous operation for 120 h (140 degrees C, 0.3 A cm- 2). The results demonstrate that the nitrogen-rich triazine-crosslinking synergistic strategy enables the advancement of high-temperature proton exchange membranes possessing superior proton conductivity and robustness, effectively enhancing their peak power density and operating lifetime.
Objective: This study aimed to evaluate the long-term degradation behavior, biostimulatory effects, and biocompatibility of a novel poly-L-lactic acid-block-polyethylene glycol/hyaluronic acid (PLLA–b–PEG/HA) composite filler for soft tissue augmentation. Methods: PLLA–b–PEG/HA microsphere properties were characterized via scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance hydrogen spectroscopy (1H NMR), thermogravimetry (TG) and differential scanning calorimetry (DSC). A 104-week in vivo rabbit model was established to systematically observe filler degradation and tissue responses. Ultrasound monitoring, histological staining, ELISA and RT-PCR were performed to assess volumetric changes, inflammatory reactions and collagen synthesis-related signaling. Results: Physicochemical property tests demonstrated that PLLA–b–PEG retains the fundamental physicochemical properties of pristine PLLA while exhibiting enhanced hydrophilicity. B-ultrasound demonstrated a presented uniform in vivo distribution without displacement or diffusion over time, confirming steady and predictable degradation. SEM verified progressive morphological degradation and porous evolution of the microspheres. The filler induced a mild, balanced inflammatory microenvironment with early expression of both pro-inflammatory (IL-12, TNF-α) and anti-inflammatory (IL-4) cytokines, which resolved gradually over time. Sustained TGF-β upregulation persisted throughout the 104-week observation period, driving continuous neocollagenesis and prominent neoelastogenesis, thereby achieving favorable and long-term tissue remodeling with excellent biocompatibility. Conclusions: The PLLA–b–PEG/HA composite filler exhibits controllable degradation properties and homeostatic regulatory effects, along with outstanding long-term biosafety and tissue integration capacity. As an ideal biostimulatory filler for soft tissue augmentation, it can effectively facilitate the regeneration of high-quality functional extracellular matrix rich in collagen fibers and elastic fibers, and holds promising clinical prospects for natural and long-lasting soft tissue filling applications.
Objective To review the research progress and application prospects of Kartogenin(KGN)in cartilage repair and tissue engineering.Methods Through a literature review,the mechanisms of KGN in cartilage repair,biomaterial composite strategies,and the resulting repair effectivenes were sorted out.Results KGN regulates multiple signaling pathways to induce mesenchymal stem cells differentiation into chondrocytes,maintain chondrocyte phenotypes,inhibit chondrocyte senescence,and promote the secretion of extracellular matrix.KGN also forms high-efficiency scaffolds with various materials,suitable for tissue engineering scaffolds of different anatomical sites and defect types,and exhibits significant cartilage regenerative effectiveness in vitro and small animal models.Conclusion Overall,KGN shows great application potential in cartilage tissue engineering.However,clinical translation still faces many challenges,which represents a key direction for future research.
Low-dielectric, transparent, and high-heat-resistant polyimide (PI) films are vital for flexible electronics and high-frequency communication devices. However, balancing these properties within intrinsic polyimides remains a significant challenge. In this work, a nonplanar diamine monomer, 2,7-bis(3,5bis(trifluoromethyl)phenyl)-9,9-bis(4-nitrophenyl)-9H-fluorene (BTFDA), containing a Cardo structure and four trifluoromethyl groups, was synthesized and copolymerized with commercial monomers to produce a series of polyimides (CPI-X). These CPI-X exhibit exceptional heat resistance, with glass transition temperatures (Tg) exceeding 350 degrees C, decomposition temperatures (Td5 %) above 530 degrees C, and low thermal expansion coefficients (CTE < 20.8 ppm/K). Additionally, they have excellent optical properties with over 92 % transparency at 450 nm and low birefringence ( An = 0.00042). They also demonstrate good hydrophobicity with low water absorption ( M a % = 0.04 %) and high-water contact angles ( C a = 97.6 degrees). Most importantly, the CPI-X films show excellent dielectric properties (Dk = 2.25, Df = 0.00365 at 1 MHz, Dk = 2.13, Df = 0.0065 at 10 GHz). Such intrinsic PI films with low D k values may be ideal candidates for next-generation interlayer media.
Cross-linking is an effective way to enhance the mechanical strength of high-temperature proton exchange membranes (HTPEMs). In this study, a series of HTPEMs based on cyanothermal cross-linked polybenzimidazole (C-PBPBI-xCN) were formulated and synthesized using cyano to achieve cross-linking via a simple heat treatment for the first time. The 4fluorobenzonitrile was grafted onto the synthesized polybenzimidazole (PBI) containing 4,5-diazafluorene and pyridine, and the cyano-grafted PBI (PBPBI-xCN) membranes were then heat-treated to cross-link the cyano groups to improve the mechanical strength of PBI, resulting in HTPEMs with good mechanical properties without sacrificing considerable proton conductivity. The prepared cyano cross-linked membranes have high oxidative stability, thermal stability, mechanical strength and phosphoric acid retention properties. The proton conductivity of the C-PBPBI-3CN membrane achieved 52.8 mS cm -1 in an anhydrous environment at 180 degrees C, which is much higher than that of uncured PBPBI-xCN.The maximum output power density of the single cell based on the C-PBPBI-3CN reached 496.2 mW cm -2 at 140 degrees C. (c) 2023 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved.
Objective:To review the research progress of different cell seeding densities and cell ratios in cartilage tissue engineering.Methods:The literature about tissue engineered cartilage constructed with three-dimensional scaffold was extensively reviewed, and the seeding densities and ratios of most commonly used seed cells were summarized.Results:Articular chondrocytes (ACHs) and bone marrow mesenchymal stem cells (BMSCs) are the most commonly used seed cells, and they can induce hyaline cartilage formation in vitro and in vivo. Cell seeding density and cell ratio both play important roles in cartilage formation. Tissue engineered cartilage with good quality can be produced when the cell seeding density of ACHs or BMSCs reaches or exceeds that in normal articular cartilage. Under the same culture conditions, the ability of pure BMSCs to build hyaline cartilage is weeker than that of pure ACHs or co-culture of both.Conclusion:Due to the effect of scaffold materials, growth factors, and cell passages, optimal cell seeding density and cell ratio need further study.
Due to the lack of blood vessels, nerves and lymphatics, articular cartilage is difficult to repair once damaged. Tissue engineering is considered to be a potential strategy for cartilage regeneration. Successful tissue engineering strategies depend on the effective combination of biomaterials, seed cells and biological factors. In our previous study, a genetically modified coculture system with chondrocytes and ATDC5 cells in an alginate hydrogel has exhibited a superior ability to enhance chondrogenesis. In this study, we further evaluated the influence of chondrocytes at various passages on chondrogenesis in the coculture system. The results demonstrated that transfection efficiency was hardly influenced by the passage number of chondrocytes. The coculture system with passage 5 (P5) chondrocytes had a better effect on chondrogenesis of ATDC5 cells, while chondrocytes in this coculture system presented higher levels of dedifferentiation than other groups with P1 or P3 chondrocytes. Therefore, P5 chondrocytes were shown to be more suitable for the coculture system, as they accumulated in sufficient cell numbers with more passages and had a higher level of dedifferentiation, which was prone to form a favorable niche for chondrogenesis of ATDC5 cells. This study may provide fresh insights for future cartilage tissue engineering strategies with a combination of a coculture system and advanced biomaterials.
The use of vaginal surgical mesh to treat pelvic organ prolapse (POP) has been associated with high rates of mesh-related complications. In the present study, we prepared new kinds of meshes based on bacterial cellulose (BC) and collagen-coated BC (BCCOL) using a laser cutting method and perforation technique. The mechanical properties of pre-implanted BC meshes, including breaking strength, suture strength and rigidity, were equal to or exceeded those of available clinically used polypropylene meshes. An in vitro cellular assay revealed that BCCOL meshes exhibited enhanced biocompatibility by increasing collagen secretion and cell adhesion. Both BC and BCCOL meshes only caused weak inflammation and were surrounded by newly formed connective tissue composed of type I collagen after implantation in a rabbit subcutaneous model for one week, demonstrating that the novel mesh is fully biocompatible and can integrate into surrounding tissues. Furthermore, a long-term (ninety days) ewe vaginal implantation model was used to evaluate foreign body reactions and suitability of BC and BCCOL meshes as vaginal meshes. The results showed that the tissue surrounding the BC meshes returned to its original physiology as muscle tissue, indicating the excellent integration of BC meshes into the surrounding tissues without triggering severe local inflammatory response post-implantation. The collagen coating appeared to induce a chronic inflammatory response due to glutaraldehyde remnants. The present exploratory research demonstrated that the developed BC mesh might be a suitable candidate for treating POP.
Parathyroid hormone (PTH) is one of the osteophilic endocrine hormones, which is involved in a variety of cellular biological processes. Previous studies have shown that PTH can inhibit the hypertrophic differentiation and apoptosis of chondrocytes and stimulate their proliferation, which has a moderate protection function on the cartilage cells by multiple signal pathways. In this paper, the mechanism of PTH in osteochondral tissue was reviewed.
Due to the lack of vascular distribution and the slow metabolism, cartilage tissue cannot repair itself, which remains a huge challenge in cartilage regeneration. Tissue engineering using stem cells appears to be a promising method for cartilage repair. Tissue engineers demonstrated that mechanical stimulation can enhance the quality of engineered cartilage, making it more similar to natural cartilage in structure and function. In this review, we summarize recent studies on the role of mechanical stimuli in chondrogenesis, focusing on the applications of extrinsic mechanical loading and the studies on mechanical properties of biomaterials in cartilage tissue engineering. This review will provide fresh insights into the potential use of mechanical stimuli for clinical use.
A new type of poly-chloromethyl styrene chelating resin (CPS-TA) containing tri-dipyridine aniline side group was synthesized from poly-chloromethyl styrene (CPS) and 4'-(4-aminophenyl)-2,2':6',2-tri-pyridine. The results of batch adsorption experiments show CPS-TA chelating resin has excellent adsorption capacity for Cu (II), Ni (II), and Pb (II), and the maximum adsorption capacity is 5.02, 3.38, and 1.27 mmol/g, respectively. The thermodynamic parameters indicate that the CPS-TA chelating resin adsorption for ions is a spontaneous process. CPS-TA chelating resin has good repeated use performance, and the CPS-TA-Cu formed after adsorption has excellent catalytic performance for H2O2 degradation of bisphenol A. The paper simulates the adsorption process through column experiments, indicating CPS-TA chelating resin could be used to adsorb and enrich heavy metal ions in wastewater, which provides a new way to effectively solve the problem of treating wastewater that contains heavy metal ions.
Poly-chloromethyl styrene (CPS) was used as a carrier to synthesize a poly-chloromethyl styrene chelating resin (CPS-DI) containing heterofluorenone side groups with 4, 5-diazafluoren-9-one. The adsorption performance of the chelating resin on Cu (II), Ni (II), and Pb (II) was studied by batch experiments. Results show that CPS-DI chelating resin has a high affinity for Cu (II), Pb (II), and Ni (II) ions. The maximum adsorption capacities of Cu (II), Pb (II), and Ni (II) are 2.55, 1.34 and 0.94 mmol/g resin, respectively. The parameters on thermodynamic give the adsorption process spontaneous, and a higher temperature is beneficial to the adsorption process. CPS-DI chelating resin has excellent reusability. The column experiment simulates the adsorption process of CPS-DI chelating resin to metal ions, indicating that CPS-DI chelating resin can treat and recover heavy metal ions such as Cu (II), Pb (II), and Ni (II), effectively solve the problem of advanced treatment of wastewater containing heavy metal ions.
Critical size bone defects are one of the most serious complications in orthopedics due to the lack of effective osteogenesis treatment. We fabricated carboxymethyl cellulose with phenol moieties (CMC-ph) microcapsules loaded with gene-modified rat bone mesenchymal stem cells (rBMSCs) that secrete hBMP2 following doxycycline (DOX) induction. The results showed that the morphology of microcapsules was spherical, and their diameters have equally distributed in the range of 100-150 μm; the viability of rBMSCs was unchanged over time. Through real-time PCR and Western blot analyses, the rBMSCs in microcapsules were found to secrete hBMP2 and to have upregulated mRNA and protein expression of osteogenesis-related genes in vitro and in vivo. Furthermore, the in vivo results suggested that the group with the middle concentration of cells expressed the highest amount of osteogenic protein over time. In this study, we showed that gene-modified rBMSCs in CMC-ph microcapsules had good morphology and viability. The BMP2-BMSCs/CMC-Ph microcapsule system could upregulate osteogenic mRNA and protein in vitro and in vivo. Further analysis demonstrated that the medium concentration of cells had a suitable density for transplantation in nude mice. Therefore, BMP2-BMSCs/CMC-Ph microcapsule constructs have potential for bone regeneration in vivo.
To address the trade-off between conductivity and stabilities for proton exchange membrane (PEM), polydopamine-modified sulfonated polyhedral oligomeric silsesquioxane (D-sPOSS) is facilely prepared and introduced into sulfonated poly(arylene ether sulfone) (SPAES) polymer matrix. The interaction between sulfonic acid groups of POSS (or of polymer chain) and basic groups of polydopamine not only can avoid the excessive swelling and maintain a high-level mechanical strength of the membrane, but also can enhance the proton hopping diffusion with uninterrupted trajectory. While the resulting D-sPOSS doped hybrid membranes exhibit prominent dimensional stability, oxidative stability and thermal stability in comparison with the sulfonated POSS (sPOSS) doped hybrid membranes and the plain SPAES membrane, the D-sPOSS doped hybrid membranes also possess superior proton conductivity, low methanol permeability and excellent single cell performance. Particularly, the proton conductivity of the hybrid membrane with 2 wt% content of D-sPOSS at 80 degrees C and 100% RH achieves 0.243 S cm(-1), which is approximately 2 times higher than that of Nafion-117 membrane, 2.4 times higher than that of the pristine SPAES membrane and 1.5 times higher than that of the sPOSS doped hybrid membrane with 2 wt% loading under the same condition.
Objective To investigate the biocompatibility of poly lactic-co-glycolic acid (PLGA)modified bacterial cellulose using smooth muscle cells. Methods Different proportions of PLGA modified bacterial cellulose were divided into five groups: the pure PLGA group (the 50P group), bacterial cellulose modified by PLA ∶PGA=50 ∶50 as the 50PB group, bacterial cellulose with poly-lactic acid(PLA) ∶poly-glycolic acid(PGA)=75 ∶25 as the 75PB group and bacterial cellulose with PLA ∶PGA=90 ∶10 as the 90PB group; the pure bacterial cellulose as the control group. The smooth muscle cells were seeded to different kinds of materials and cultured for 7 d. The situation of smooth muscle cells on different materials was observed by electronic migroscope(SEM)and determined by live/dead staining. The cell proliferation on the materials was determined by cell counting kit-8(CCK-8) test. The data of cell survival rate and proliferation rate were analyzed by one-way ANOVA and SNK test. Results The smooth muscle cells in all the groups adhered well to the materials on the 3rd day according to SEM observation. The live/dead staining result showed that smooth muscle cells of all the groups distributed uniformly and grow flourishly(F=1.454, P>0.05). The CCK-8 data indicated that the growth of smooth muscle cells in different groups had no difference on the 3rd day and 5th day(3 d F=1.672, P>0.05; 5 d F=1.19, P>0.05). On the 7th day the cells both in the 50PB group and the control group showed superior proliferation to those in the 90PB group and the 75PB group(F=13.328, P<0.01). Conclusion The biocompatibility of PLGA (PLA ∶PGA=50 ∶50) modified bacterial cellulose is better than other PLGA proportion modified bacterial cellulose, which is potential biomaterial for tissue repair. Key words: Cellulose; Polylactic acid-polyglycolic acid copolymer; Myocytes, smooth muscle; Biocompatible materials
Articular cartilage repair after injury is a great challenge worldwide due to its nerveless and avascular features. Tissue engineering is proposed as a promising alternative for cartilage regeneration. In this study, an adenoviral vector carrying the transforming growth factor-β3 (TGF-β3) gene was constructed and introduced into dedifferentiated chondrocytes, which were then cocultured with ATDC5 cells in an alginate hydrogel system. The results showed that the experimental groups exhibited better cell viability and higher levels of cartilage-related genes than the control groups. In this coculture system, the chondrogenic differentiation of ATDC5 cells was effectively induced by TGF-β3 and other latent cytokines that were produced by the transfected chondrocytes. Thus, this method can avoid the degradation of exogenous TGF-β3, and it can protect ATDC5 cells during virus transfection to maintain cell viability and chondrogenic differentiation capability. Taken together, this study provides fresh insights for applying this genetically manipulated coculture system to cartilage repair in the future.
用成体干细胞修复软骨损伤是目前的研究热点,其中骨髓间充质干细胞( bone marrow mesenchymal stem cells, BM-MSCs)可以诱导成软骨细胞,转化生长因子 β( transforming growth factorβ,TGF-β)可以通过活化成软骨标志物诱导BM-MSCs成软骨,但分化软骨细胞容易肥大且生长因子可能引发免疫反应. 有研究者致力于寻找适合的药物来诱导BM-MSCs成软骨分化,有报道视黄醇酸受体是一种可能的药理作用靶点[1]. LE135是一种视黄醇酸受体拮抗剂,化学式为C29 H30 N2 O2 ,分子质量438. 56,不溶于水,溶于二甲亚砜. 本研究就LE135在大鼠BM-MSCs成软骨分化诱导中的可能作用进行了初步的探索.
目的 探讨多学科综合诊疗(MDT)联合以问题为基础的学习(PBL)教学法对老年髋部骨折的临床教学效果.方法 选取2017年1月至2018年12月广州医科大学五年制临床医学系在广州医科大学附属第一医院骨科进行临床实习同级学生共90名,随机分为试验组(MDT模式下PBL组)45名和对照组[传统教学以讲授为基础的学习(LBL)组]45名.分别按照各组教学方式进行老年髋部骨折临床示教,比较2组的教学效果与教学满意度.结果 试验组理论考试成绩较对照组高,但差异无统计学意义(P>0.05);而试验组的病例分析成绩较对照组高,同时教学满意度亦明显高于对照组,差异均有统计学意义(P<0.05).结论 MDT模式下PBL教学法在老年髋部骨折临床教学中收到良好的效果,可提高学生的自学能力,值得在临床教学中进一步推广.