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Cartilage tissue engineering involves the invention of novel implantable cartilage replacement materials to help heal cartilage injuries that do not heal themselves, aiming to overcome the shortcomings of current clinical cartilage treatments. Chitosan has been widely used in cartilage tissue engineering because of its similar structure to glycine aminoglycan, which is widely distributed in connective tissues. The molecular weight, as an important structural parameter of chitosan, affects not only the method of chitosan composite scaffold preparation but also the effect on cartilage tissue healing. Thus, this review identifies methods for the preparation of chitosan composite scaffolds with low, medium and high molecular weights, as well as a range of chitosan molecular weights appropriate for cartilage tissue repair, by summarizing the application of different molecular weights of chitosan in cartilage repair in recent years. [ABSTRACT FROM AUTHOR]

Highlights • A rapid-prototyping angle-scanning Surface plasmon resonance was presented. • FDM 3D printing technology was utilized to realize rapid prototyping and cost down manufacture. • Aptasensor was utilized to detect glycated hemoglobin (HbA1c) directly. • The linear detection response of HbA1c appeared in the range from 18 to 147 nM with a detection limit of 1 nM. Abstract Diabetes mellitus is one of the most common noncommunicable diseases in the world. Fasting blood glucose level is one of the diabetes diagnostic criteria, but it is readily affected by stress, exercise and many other factors. Glycated hemoglobin (HbA1c) is an important clinical index for diabetes and related diseases. In this study, a cheaper, rapid-prototyping, high-sensitivity angle-scanning surface plasmon resonance (SPR) was developed by fused deposition modeling (FDM) 3D printing technology for HbA1c detection. The sensor chip is based on an aptamer that has high affinity and high specificity to HbA1c. The results showed that this HbA1c-specific aptamer had high specificity for HbA1c, and the calculated K D was 6.13 × 10−8 M. The linear detection response of HbA1c appeared in the range of 18–147 nM, with a detection limit of 1 nM. This SPR HbA1c detection system could be a promising platform for developing clinical point-of-care diagnostic applications. [ABSTRACT FROM AUTHOR]

After tendon-repair surgery, adhesion between the surgical tendon and the synovial sheath is often presented resulting in poor functional repair of the tendon. This may be prevented using a commercially available mechanical barrier implant, Seprafilm, which is composed of hyaluronan (HA) and carboxymethyl cellulose hydrogels. In a rat model, prepared membranes of various compositions of gellan gum (GG), xanthan gum (XG) and HA as well as Seprafilm were wrapped around repaired tendons and the adhesion of the tendons was examined grossly and histologically after 3 weeks of healing. Certain formulations of the XG/GG/HA hydrogel membranes reduced tendon adhesion with equal efficacy but without reducing the tendon strength compared to Seprafilm. The designed membranes swelled rapidly and blanketed onto the tendon tissue more readily and closely than Seprafilm. Also they degraded slowly, which allowed the membranes to function as barriers for extended periods. [ABSTRACT FROM AUTHOR]

Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure of a sphere that contains smaller microspheres which then encapsulate chemicals, drugs and/or cells. The volvox spheres were produced via a high-voltage electrostatic field system, using alginate as the primary material. Encapsulated materials tested in this study include staining dyes, nuclear fast red and trypan blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The external morphology of the volvox spheres was observed via electron microscopy whereas the internal structure of the volvox spheres was observed via an optical microscope with the aid of the staining dyes, since alginate is colorless and transparent. The diameter of the microspheres was about 200 to 300μm, whereas the diameter of the volvox spheres was about 1500μm. Volvox spheres were durable, retaining about 95% of their mass after 4weeks. Factors affecting entrapment efficiency, such as temperature and concentration of the bivalent cross-linker, were compared followed by a 7-day in vitro release study. The encapsulation efficiency of CytC within the microspheres was higher at cold (~4°C) and warm (~50°C) temperatures whereas temperature has no obvious effect on the BSA encapsulation. High crosslinking concentration (25% w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but not for CytC. Furthermore, volvox spheres showed a different release pattern of BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite the fact that the mechanisms behind remain unclear and further investigation is required, this study demonstrates the potential of the volvox spheres for drug delivery. [ABSTRACT FROM AUTHOR]

An antiadhesion membrane made from gellan gum was fabricated and characterized. A 12-µm-thick membrane of gellan gum was prepared and reacted with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to obtain a cross-linked membrane (G/A70) with 87% gel content and a tensile strength of 46.5 MPa. In vivo, the G/A70 membrane had 90% less tissue adhesion. Inflammation-related and extracellular matrix protein gene expression in a rat model of abdominal surgery was found by real-time quantitative reverse transcription polymerase chain reaction analysis. On day 3, after surgery, the gene expression of ceruloplasmin and type V collagen in the G/A70-treated group was 1.9 and 0.3 times that of the control group, respectively. The G/A70 membrane elicited mild inflammation but suppressed type V collagen synthesis and reduced the occurrence of tissue adhesion. These findings provide insights into the properties of gellan gum antiadhesion membranes and help to overcome problems involving tissue adhesions in surgical procedures. [ABSTRACT FROM AUTHOR]

Abstract: The insertion of dental filling into the dental cavity is a common method of maintaining the space and shape of dental cavities after dental extractions. To develop novel dental fillings meeting clinical requirements, gellan gum (GG) is selected in this study to prepare fillings with specific characteristics by modulating gellan gum concentrations (denoted as GG-DF). The results indicate that the microstructure, porosity, and compression modulus of 1.5% and 1.75% GG-DF are similar to a commercially product (Teruplug®) and with good blood absorption capacity. The degradation ratio of Teruplug® in an amylase/phosphate buffer solution after 4weeks is 80% whereas that of 1.5% and 1.75% GG-DF is 65%. Cell migration studies confirmed that the migration ability of fibroblast was significantly inhibited by gellan gum. These results demonstrate that 1.5% and 1.75% GG-DF are potentially viable for developing into dental fillings. [Copyright &y& Elsevier]

Using a recently established method to prepare hyaluronan/collagen II (HA/Col II) microspheres for a novel biomaterial to couple with living cells/tissues, this animal model study evaluated the effects on a 4-week healing process of chondral defects by the implantation of allogenous chondrocyte-seeded HA/Col II microspheres that had been cultured in vitro for 7 days prior to implantation compared with unseeded HA/Col II microspheres or an untreated wound. Four weeks postsurgery, the untreated group's defect was filled with translucent soft tissue. At the same time, the edges and demarcation lines of the healing defects that were implanted with either HA/Col II microspheres or chondrocyte-seeded HA/Col II microspheres were infused yet recognizable. Furthermore, the new tissues were well integrated into the surrounding articular cartilage. Less glycosaminoglycan (GAG) staining was observed in the defects implanted with HA/Col II microspheres, which indicated that most of the repair tissues were derived from fibrocartilage formation. Conversely, more GAG staining appeared in the defect implanted with chondrocyte-seeded HA/Col II microspheres, which demonstrated a higher level of hyaline cartilage regeneration. Due to the short healing period assigned to this study, the repaired cartilage showed limited incorporation into the surrounding host cartilage and some loose connection to the subchondral bone. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to prepare and evaluate chitosan dressings treated with sodium hydroxide (NaOH) and/or sodium tripolyphosphate (Na5P3O10) for haemostatic use. The pure sodium hydroxide-gelled chitosan dressing (CS-B) had water contents (about 95%) and porosities (about 85%) which were similar to those of commercially available chitosan-based products. The CS-B dressing also exhibited homogeneously sized and penetrating pores throughout, whereas the commercially available Clo-Sur PAD showed porous lamellar structures inside and Instant Clot Pad exhibited a heterogeneous pore size distribution. Additionally, the CS-B dressing was flexible and resilient, free of odour and able to recover completely after compression in a hydrated state. Finally, the CS-B sponge absorbed blood quickly, accelerating blood clotting, enhancing red blood cell adhesion and maintaining its original shape after haemostatic testing. [Copyright &y& Elsevier]

In recent years, with the rise of global diabetes, a growing number of subjects are suffering from pain and infections caused by the invasive nature of mainstream commercial glucose meters. Non-invasive blood glucose monitoring technology has become an international research topic and a new method which could bring relief to a vast number of patients. This paper reviews the research progress and major challenges of non-invasive blood glucose detection technology in recent years, and divides it into three categories: optics, microwave and electrochemistry, based on the detection principle. The technology covers medical, materials, optics, electromagnetic wave, chemistry, biology, computational science and other related fields. The advantages and limitations of non-invasive and invasive technologies as well as electrochemistry and optics in non-invasives are compared horizontally in this paper. In addition, the current research achievements and limitations of non-invasive electrochemical glucose sensing systems in continuous monitoring, point-of-care and clinical settings are highlighted, so as to discuss the development tendency in future research. With the rapid development of wearable technology and transdermal biosensors, non-invasive blood glucose monitoring will become more efficient, affordable, robust, and more competitive on the market. [ABSTRACT FROM AUTHOR]

• Anti HCT interference blood glucose sensors based on fiber paper-based screen-printed carbon electrode were demonstrated. • The paper-based glucose sensor can reduce HCT interference significantly with HCT range 20% to 70%. • In consensus error grid, 95% of the data points lie within zones A and B. As the number of diabetic patients increases year by year, the demand for a self-monitoring blood glucose test also increases. Additionally, more in-depth studies of blood glucose biosensors have led to increasing accuracy requirements. However, at present, most enzyme glucose sensors have difficulty solving issues related to hematocrit (HCT) interference. Most studies on anti-HCT interference in blood glucose sensing have mainly focused on correction factors, such as glucose correction, and electrical impedance or resistivity characteristics to correct the impact of HCT. In this work, we developed an anti-HCT-interference blood glucose sensor based on a fiber paper-based screen-printed carbon electrode with a mediator (potassium ferricyanide) and glucose oxidase (GOD), which were fixed through inkjet printing. When testing whole blood samples with HCT levels of 20%–70% and a fluid dropping method, the results of a consensus error grid analysis showed that 91% of the data points lied within zones A and B. The glucose sensor was exclusively designed with a 16 μL chamber in the working area of the sensor. When the testing fluid was taken in by capillary sucking, the effect of HCT was further reduced, and 95% of the data points lied within zones A and B in the consensus error grid. [ABSTRACT FROM AUTHOR]

Keloid scarring is an abnormal scar disease characterised by excessive proliferation of fibroblasts and over-deposition of collagen during wound healing. Although various treatments for keloid scars have been developed, preventive medicine is believed to be a promising strategy. The skin barrier limits the gentle topical administration of medicaments such as creams and hydrogel dressings, resulting in reduced therapeutic efficacy. In recent years, microneedles (MNs) have been regarded as an appreciable device for topical administration without inducing side effects, and they are painless and do not cause bleeding. In this study, an MN patch with controlled transdermal dual-drug release was developed to achieve combinatory treatment of keloid scars using a heterogeneous gelatin-structured composite MN. Gelatin hydrogel was used as a substrate to load gallic acid (GA) and quercetin-loaded amphiphilic gelatin nanoparticles to fabricate dual-drug heterogeneous composite MNs. The results of the insertion test and mechanical properties of the MNs showed that the heterogeneous composite MN patches could be self-pressed into the stratum corneum and control dual-drug release at different time periods. GA was released at an earlier stage to retard the proliferation of fibroblasts, and quercetin was released at a later stage as a strong antioxidant to erase the generation of reactive oxygen species. Furthermore, real-time quantitative polymerase chain reaction data indicated that the gene expression of fibroblasts (such as Col I and III) was downregulated in the dual-drug system. The above results demonstrate that using heterogeneous composite MNs with the combination of dual-drug pharmacology is beneficial for preventing keloid scar formation. [ABSTRACT FROM AUTHOR]

Volvox sphere is a bio-mimicking concept of a biomaterial structure design able to encapsulate chemicals, drugs and/or cells. The aim of this study was to prepare Volvox spheres encapsulating AML12 liver cells and mesenchymal stem cells (MSCs) via a high voltage electrostatic field system. The results demonstrated that AML12 liver cells and MSCs could be successfully encapsulated into the inner spheres and the outer sphere of the Volvox spheres. The improved cell viability of MSCs was achieved by the addition of collagen and polyethylene glycol into the preparation components of the Volvox spheres. Collagen material potentially provides extracellular matrix-like structure for cell adhesion while polyethylene glycol provides a void/loose space for permeability of metabolites. The encapsulated MSCs were able to differentiate into hepatocytes or hepatocyte-like cells and express liver cell markers including albumin, alpha feto-protein and cytokeratin 18. The encapsulated cells secreted albumin to about 140 ng on day 14. Based on these observations, we conclude that Volvox spheres can be used as an alternative approach to encapsulate multiple types of cells, here AML12 hepatocyte cell line and MSCs. Nevertheless, efforts are still needed to improve the viability of the encapsulated cells and increase the differentiation of MSCs into functional liver cells. [ABSTRACT FROM AUTHOR]

Glycated hemoglobin (HbA1c) has been widely explored as an important marker for monitoring and diagnosing diabetes. Due to the advantages of high selectivity, easy preparation, and convenient preservation of aptamers, research on glycated hemoglobin detection utilizing aptasensors has received much attention in recent years. However, factors such as the pH and the salt concentration of the solution and the structure of the aptamer could influence the interactions between HbA1c and the aptamer. In this study, the factors were evaluated using surface plasmon resonance (SPR). The results show that the pH and the salt concentration can greatly affect the formation of a complex between the aptamer and HbA1c. In the stereostructure of the aptamer, loop L1 may be an important motif for recognizing glycated hemoglobin. In addition, the best condition for detecting HbA1c was at pH 6, with a high sensitivity and a low limit of detection(LOD) (1.06 × 10−3 RU nM /2.55 nM). The results also demonstrated that the use of an SPR aptamer biosensor can be a sensitive technique to improve the accuracy and correctness of HbA1c measurement. Highly sensitive HbA1c detection using SPR aptasensor is achieved under the circumstance of optimized environmental parameters and aptamer structure evaluation. Image 1 • This is the first investigation of the interaction between aptamer and HbA1c. • This spontaneous interaction can be attributed to enthalpy-entropy compensation. • This methodology could provide serve as an aptamer assay for target binding ability. [ABSTRACT FROM AUTHOR]

Extracellular matrix has an important part of the role in tissue engineering and regenerative medicine, so it is necessary to understand the various interactions between cells and extracellular matrix. Type II collagen and hyaluronic acid are the major structural components of the extracellular matrix of articular cartilage, and they are involved in fibril formation, entanglement and binding. The aim of this study was to prepare type II collagen fibrils with surface grafted with hyaluronic acid modified at the reducing end. The topographic pattern of type II collagen fibrils showed a significant change after the surface coupling of hyaluronic acid according to atomic force microscopy scanning. The presence of hyaluronic acid on the type II collagen fibrillar surface was confirmed by the specific binding of nanogold labelled with lectin. No significant increase in cell proliferation was detected by a WST-1 assay. According to histochemical examination, the maintenance of the round shape of chondrocytes and increased glycosaminoglycan secretion revealed that these cell pellets with Col II- g -hyaluronic acid molecules contained un-dedifferentiated chondrocytes in vitro. In the mixture with the 220-kDa Col II- g -hyaluronic acid copolymer, the expression of type II collagen and aggrecan genes in chondrocytes increased as demonstrated by real-time polymerase chain reaction analysis. Experimental results show that the amount of hyaluronic acid added during culturing of chondrocytes can maintain the functionality of chondrocytes and thus allow for increased cell proliferation that is suitable for tissue repair of human cartilage. [ABSTRACT FROM AUTHOR]

Due to limited self-healing capacity in cartilages, there is a rising demand for an innovative therapy that promotes chondrocyte proliferation while maintaining its biofunctionality for transplantation. Chondrocyte transplantation has received notable attention; however, the tendencies of cell de-differentiation and de-activation of biofunctionality have been major hurdles in its development, delaying this therapy from reaching the clinic. We believe it is due to the non-stimulative environment in the injured cartilage, which is unable to provide sustainable physical and biological supports to the newly grafted chondrocytes. Therefore, we evaluated whether providing an appropriate matrix to the transplanted chondrocytes could manipulate cell fate and recovery outcomes. Here, we proposed the development of electrosprayed nanoparticles composed of cartilage specific proteins, namely collagen type II and hyaluronic acid, for implantation with pre-seeded chondrocytes into articular cartilage defects. The fabricated nanoparticles were pre-cultured with chondrocytes before implantation into injured articular cartilage. The study revealed a significant potential for nanoparticles to support pre-seeded chondrocytes in cartilage repair, serving as a protein delivery system while improving the survival and biofunctionality of transplanted chondrocytes for prolonged period of time. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a globally occurring articular cartilage degeneration disease that adversely affects both the physical and mental well-being of the patient, including limited mobility. One major pathological characteristic of OA is primarily related to articular cartilage defects resulting from abrasion and catabolic and proinflammatory mediators in OA joints. Although cell therapy has hitherto been regarded as a promising treatment for OA, the therapeutic effects did not meet expectations due to the outflow of implanted cells. Here, we aimed to explore the repair effect of magnetized chondrocytes using magnetic amphiphilic-gelatin nanocarrier (MAGNC) to enhance cellular anchored efficiency and cellular magnetic guidance (MG) toward the superficial zone of damaged cartilage. The results of in vitro experiments showed that magnetized chondrocytes could be rapidly guided along the magnetic force line to form cellular amassment. Furthermore, the Arg-Gly-Asp (RGD) motif of gelatin in MAGNC could integrate the interaction among cells to form cellular stacking. In addition, MAGNCs upregulated the gene expression of collagen II (Col II), aggrecan, and downregulated that of collagen I (Col I) to reduce cell dedifferentiation. In animal models, the magnetized chondrocytes can be guided into the superficial zone with the interaction between the internal magnetic field and MAGNC to form cellular stacking. In vivo results showed that the intensity of N-sulfated-glycosaminoglycans (sGAG) and Col II in the group of magnetized cells with magnetic guiding was higher than that in the other groups. Furthermore, smooth closure of OA cartilage defects was observed in the superficial zone after 8 weeks of implantation. The study revealed the significant potential of MAGNC in promoting the high-density stacking of chondrocytes into the cartilage surface and retaining the biological functions of implanted chondrocytes for OA cartilage repair. [ABSTRACT FROM AUTHOR]

Background: Low-intensity pulsed ultrasound (LIPUS) regiment has been used to treat fractures with non-union and to promote bone union in general. The effect of LIPUS on articular cartilage metabolism has been characterized. Yet, the effect of LIPUS to repair articular cartilage injury remains unclear in vivo.Methods: We designed a study to investigate the effect of LIPUS on articular cartilage repairing in a rabbit severe cartilage injury model. Eighteen rabbits were divided into three groups: Sham-operated group, operated group without-LIPUS-treatment, operated group with-LIPUS-treatment (a daily 20-minute treatment for 3 months). Full-thickness cartilage defects were surgically created on the right side distal femoral condyle without intending to penetrate into the subchondral bone, which mimicked severe chondral injury. MR images for experimental joints, morphology grading scale, and histopathological Mankin score were evaluated.Results: The preliminary results showed that the operated groups with-LIPUS-treatment and without-LIPUS-treatment had significantly higher Mankin score and morphological grading scale compared with the sham-operated group. However, there was no significant difference between the with-LIPUS-treatment and without-LIPUS-treatment groups. Cartilage defects filled with proliferative tissue were observed in the with-LIPUS-treatment group grossly and under MR images, however which presented less up-take under Alcian blue stain. Furthermore, no new deposition of type II collagen or proliferation of chondrocyte was observed over the cartilage defect after LIPUS treatment.Conclusion: LIPUS has no significant therapeutic potential in treating severe articular cartilage injury in our animal study. [ABSTRACT FROM AUTHOR]

Background: Leiomyoma is a benign tumor of smooth-muscle origin. They most commonly derived from the uterus. Besides, they were also usually diagnosed in the gastrointestinal tract, skin, and mucous membranes. However, it rarely occurs in the bone. Case presentation: The authors reported one case of 56-year-old male with intraosseous leiomyoma of the distal femur. Initially, the patient felt left knee pain for 1 year. Radiographs film disclosed an ill-defined osteolytic lesion with thinning cortex over left distal femoral medial condylar region. Computed tomography (CT) revealed homogenous radiolucent lesion with thinning cortex over the metaphysis of distal femur. Magnetic resonance imaging showed focal marrow replacement by tumor. CT-guide biopsy was performed, and the pathology showed a picture of leiomyoma. Since the definite diagnosis, the lesion was treated with en-bloc resection and endoprosthetic knee joint reconstruction. Satisfied result and disease free were achieved during follow-up. Conclusions: Intraosseous leiomyoma of the extremities is difficult to be diagnosed due to extraordinarily rare. This rare benign tumor should be included in the differential diagnosis of any relatively intraosseous lesion with benign imaging findings. This is the first published case of primary intraosseous leiomyoma of distal femur after literature reviews. [ABSTRACT FROM AUTHOR]

Abstract: Designing a surface recognition layer with high anti-fouling ability, high affinity, and high specificity is an important issue to produce high sensitivity biosensing transducers. In this study, a self-assembled monolayer (SAM) consisting of a homogeneous mixture of oligo(ethylene glycol) (OEG)-terminated alkanethiolate and mercaptohexadecanoic acid (MHDA) on Au was employed for immobilizing troponin T antibody and applied in detecting cardiac troponin T by using surface plasmon resonance (SPR). The mixed SAM showed no phase segregation and exhibited human serum albumin resistance, particularly with an antibody-immobilized surface. X-ray photoemission spectra revealed that the chemical composition ratio of OEG to the mixed SAM was 69% and the OEG packing density was 82%. The specific binding of troponin T on the designed surface indicated a good linear correlation (R =0.991, P <0.0009) at concentrations lower than 50μgmL−1 with the limit of detection of 100ngmL−1 using a SPR measuring instrument. It is concluded that the mixed SAM functions as designed since it has high detection capability, high accuracy and reproducibility, as well as shows strong potential to be applied in rapid clinical diagnosis for label-free detection within 2min. [Copyright &y& Elsevier]

Abstract: Using excitation polarization-resolved second harmonic generation (SHG) microscopy, we measured SHG intensity as a function of the excitation polarization angle for type I and type II collagens. We determined the second order susceptibility (χ(2)) tensor ratios of type I and II collagens at each pixel, and displayed the results as images. We found that the χ(2) tensor ratios can be used to distinguish the two types of collagen. In particular, we obtained χ zzz/χ zxx = 1.40 ± 0.04 and χ xzx/χ zxx = 0.53 ± 0.10 for type I collagen from rat tail tendon, and χ zzz/χ zxx = 1.14 ± 0.09 and χ xzx/χ zxx = 0.29 ± 0.11 for type II collagen from rat trachea cartilage. We also applied this methodology on the label-free imaging of engineered cartilage tissue which produces type I and II collagen simultaneously. By displaying the χ(2) tensor ratios in the image format, the variation in the χ(2) tensor ratios can be used as a contrast mechanism for distinguishing type I and II collagens. [Copyright &y& Elsevier]

Platelet gels (PG), activated by bovine thrombin (BT), have increasingly been used in orthopedic surgery. However, BT may induce immunological reactions and carry potential viral and prion risks. To avoid these side effects, thrombin derived from human plasma (human thrombin, HT) is becoming the preferred platelet activator to prepare PG. However, limited experience and data on the clinical benefits of HT-generated PG (HTPG) in orthopedic surgery is reported. Consequently, we designed and performed a series of studies in dogs to compare the impacts of promotion of bone growth by an artificial bone substitute (Osteoset®) in combination with HTPG or without it in the spinal repair experiments. X-ray observations and histological studies were performed at predetermined periods post-operation. The preliminary results revealed the preparation of HTPG was easy and required less than 30 minutes. HTPG was capable of embedding the artificial bone substitute Osteoset® to prepare a sticky and easily manipulated composite for the application into spinal defect. We found HTPG exhibited enhancement of grafting capacity in consolidation of bone mass. After 12 weeks, tissue reconstruction reached approximately 80% of the injury defects when treated by HTPG/Osteoset® combination, but only 30∼40% in the absence of HTPG. The physiological activity of artificial bone substitute combined with PG activated by HT may therefore open beneficial prospects for more successful and safer bone formation in spine procedures in the near future. [ABSTRACT FROM AUTHOR]

Although traditional 3D scaffolds or biomimetic hydrogels have been used for tissue engineering and regenerative medicine, soft tissue microenvironment usually has a highly anisotropic structure and a dynamically controllable deformation with various biomolecule distribution. In this study, we developed a hierarchical hybrid gelatin methacrylate-microcapsule hydrogel (HGMH) with Neurotrophin-3(NT-3)-loaded PLGA microcapsules to fabricate anisotropic structure with patterned NT-3 distribution (demonstrated as striped and triangular patterns) by dielectrophoresis (DEP). The HGMH provides a dynamic biomimetic sinuate-microwrinkles change with NT-3 spatial gradient and 2-stage time-dependent distribution, which was further simulated using a 3D finite element model. As demonstrated, in comparison with striped-patterned hydrogel, the triangular-patterned HGMH with highly anisotropic array of microcapsules exhibits remarkably spatial NT-3 gradient distributions that can not only guide neural stem cells (NSCs) migration but also facilitate spinal cord injury regeneration. This approach to construct hierarchical 4D hydrogel system via an electromicrofluidic platform demonstrates the potential for building various biomimetic soft scaffolds in vitro tailed to real soft tissues. [Display omitted] [ABSTRACT FROM AUTHOR]

This study focuses on preparation and valuation of the biodegradable, native, and modified gelatin film as screen-printing substrates. Modified gelatin film was prepared by crosslinking with various crosslinking agents and the electrode array was designed by screen-printing. It was observed that the swelling ratio of C-2, crosslinked with glutaraldehyde and EDC/NHS (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide) was found to be lower (3.98%) than that of C-1 (crosslinked with only glutaraldehyde) (8.77%) and C-0 (without crosslinking) (28.15%). The obtained results indicate that the swelling ratios of both C-1 and C-2 were found to be lower than that of C-0 (control one without crosslinking). The Young's modulus for C-1 and C-2 was found to be 8.55 ± 0.57 and 23.72 ± 2.04 kPa, respectively. Hence, it was conveyed that the mechanical strength of C-2 was found to be two times higher than that of C-l, suggesting that the mechanical strength was enhanced upon dual crosslinking in this study also. The adhesion study indicates that silver ink adhesion on the gelation surface is better than that of carbon ink. In addition, the electrical response of C-2 with a screen-printed electrode (SPE) was found to be the same as the commercial polycarbonate (PC) substrate. The result of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay suggested that the silver SPE on C-2 was non-cytotoxic toward L929 fibroblast cells proliferation. The results indicated that C-2 gelatin is a promising material to act as a screen-printing substrate with excellent biodegradable and biocompatible properties. [ABSTRACT FROM AUTHOR]

Articular cartilage defect is a common disorder caused by sustained mechanical stress. Owing to its nature of avascular, cartilage had less reconstruction ability so there is always a need for other repair strategies. In this study, we proposed tissue-mimetic pellets composed of chondrocytes and hyaluronic acid-graft-amphiphilic gelatin microcapsules (HA-AGMCs) to serve as biomimetic chondrocyte extracellular matrix (ECM) environments. The multifunctional HA-AGMC with specific targeting on CD44 receptors provides excellent structural stability and demonstrates high cell viability even in the center of pellets after 14 days culture. Furthermore, with superparamagnetic iron oxide nanoparticles (SPIOs) in the microcapsule shell of HA-AGMCs, it not only showed sound cell guiding ability but also induced two physical stimulations of static magnetic field(S) and magnet-derived shear stress (MF) on chondrogenic regeneration. Cartilage tissue-specific gene expressions of Col II and SOX9 were upregulated in the present of HA-AGMC in the early stage, and HA-AGMC+MF+S held the highest chondrogenic commitments throughout the study. Additionally, cartilage tissue-mimetic pellets with magnetic stimulation can stimulate chondrogenesis and sGAG synthesis. [ABSTRACT FROM AUTHOR]