Cell Carriers Research Articles

Living Microneedle Patch with Adipose‐Derived Stem Cells Embedding for Diabetic Ulcer Healing

AbstractStem cells have demonstrated values in diabetic ulcer (DU) treatments. Challenges in this area are focused on enhancing the localized curative effects of stem cells and improving diabetic wound healing efficiently. Herein, a novel living microneedle (MN) patch is presented as a localized delivery system of bioactive platelet derived growth factor D (PDGF‐D) and human adipose‐derived stem cells (ADSCs) for DU wound treatment. Compared with traditional complicated stem cell carriers, the MN patch can keep stem cell viability for ADSCs encapsulation and delivery, and possesses good mechanical strengths to penetrate the local skin wounds noninvasively. It is demonstrated that the delivery ADSCs are with the abilities of angiogenesis promotion during the DU wound healing; while the additive PDGF‐D can contribute significantly to the proliferation of ADSCs, strengthening the cell function of ADSCs and further facilitating the healing processes. Thus, living MN patches accelerate vascularization, tissue regeneration, and collagen deposition in a wounded diabetic mouse model, suggesting their potential application to DU wound healing and other therapeutic applications.

Designer injectable matrices of photocrosslinkable carboxymethyl cellulose methacrylate based hydrogels as cell carriers for gel type autologous chondrocyte implantation (GACI)

Gel-type autologous chondrocyte implantation (GACI) is the fourth-generation therapeutic strategy that has been introduced to address the limitations of earlier generation strategies, especially problems related to cell leakage upon implantation and loss of chondrocyte functionality owing to the dedifferentiation of cells in culture and fibrocartilage formation. In GACI, an injectable gel system is used, which acts as the cell carrier. However, the maintenance of the morphology and redifferentiation of chondrocytes with appropriate biofunctionality are major challenges in this technique. In this study, we prepared a photocrosslinkable injectable hydrogel based on carboxymethyl cellulose-methacrylate (CMC-MA) and polyethylene glycol diacrylate (PEGDA) and evaluated chondrocyte–matrix interactions and biofunctionality on different blend ratios of the gels with varying stiffness. Cell–matrix interaction was evaluated by immunostaining for actin filaments via phalloidin and cell adhesion markers such as focal adhesion kinase (FAK), integrin β1, and integrin αV. This study indicates that the stiffness of the substrates, along with the material chemistry, is a crucial factor when selecting an injectable gel-based system. Stiffer gels (2:8 CMC-MA/PEGDA) showed good chondrocyte cell attachment and growth with maintenance of the redifferentiated phenotype; therefore, they can be considered as an ideal matrix for GACI technique.

Molecular Mechanism of Hydrotropic Properties of GTP and ATP.

Hydrotropes are small amphiphilic compounds that increase the aqueous solubility of hydrophobic molecules. Recent evidence suggests that adenosine triphosphate (ATP), which is the primary energy carrier in cells, also assumes hydrotropic properties to prevent the aggregation of hydrophobic proteins, but the mechanism of hydrotropy is unknown. Here, we compare the hydrotropic behavior of all four biological nucleoside triphosphates (NTPs) using molecular dynamics (MD) simulations. We launch all atom MD simulations of aqueous solutions of NTPs [ATP, guanosine triphosphate (GTP), cytidine triphosphate (CTP), and uridine triphosphate (UTP)] with pyrene, which acts both as a model hydrophobic compound and as a spectroscopic reporter for aggregation. GTP prevents pyrene aggregation effectively. Dissolution is not achieved in the presence of CTP and UTP. The higher stability of the base stacking in guanine is responsible for the higher hydrotropic efficiency of GTP. Consistent with the simulations, spectroscopic measurements also suggest that the hydrotropic activity of GTP is higher than ATP. Stacking of aromatic pyrene with the aromatic base of NTPs is a characteristic feature of this hydrotropic property. Both ATP and GTP also dissolve clusters of di- and tripeptides containing tryptophan but with equal potency. Importantly, the presence of aromatic amino acids is a necessary condition for the hydrotropic potency of ATP and GTP. Our results can have broad implications for hydrotrope design in the pharmaceutical industry, as well as the possibility of cells employing GTP as a hydrotrope to regulate the hydrophobic protein aggregation in membrane-less biological condensates.

Polyhydroxy compound modifying SnO2 for high-performance and stable perovskite solar cells

Electron transport layer (ETL) is one of the key functional layers for extracting carriers in perovskite solar cells (PSCs). SnO2 with high electron mobility and excellent energy level matching with adjacent perovskites has been considered an ideal electron transport material with great application prospects. However, surface defects always exist on the SnO2 films prepared by solution method, which will inevitably lead to non-radiation recombination at the interface of SnO2 ETL/perovskite. To further improve the performance of PSCs, the defects should be effectively suppressed. Herein, an interfacial engineering strategy is adopted to eliminate the surface defects and improve the interface performance by passivating the SnO2 electron transport layer with sodium L-ascorbate (SLA). After the SLA treatment, the interfacial defects of SnO2/perovskite film were reduced significantly and the electron transport was effectively facilitated by the denser SnO2 layer, finally improving the power conversion efficiency (PCE) of PSCs. Besides, SLA neutralized the alkalinity of SnO2 film, simultaneously improving the efficiency and stability of the device. As a result, the PCE of FA0.74MA0.19Cs0.07PbI2.81Cl0.19 PSCs with active area of 0.09 cm2 was increased from 20.32 % to 22.70 %, and the larger area PSCs with active area 1.00 cm2 obtained a high PCE of 19.83 %. This work presents a convenient and effective passivation strategy for improving the ETL to promote the development of perovskite photovoltaic devices.

Sphingolipids in Atherosclerosis: Chimeras in Structure and Function.

Atherosclerosis—a systemic inflammatory disease—is the number one cause of mortality and morbidity worldwide. As such, the prevention of disease progression is of global interest in order to reduce annual deaths at a significant scale. Atherosclerosis is characterized by plaque formation in the arteries, resulting in vascular events such as ischemic stroke or myocardial infarction. A better understanding of the underlying pathophysiological processes at the cellular and molecular level is indispensable to identify novel therapeutic targets that may alleviate disease initiation or progression. Sphingolipids—a lipid class named after the chimeric creature sphinx—are considered to play a critical and, metaphorically, equally chimeric regulatory role in atherogenesis. Previous studies identified six common sphingolipids, namely dihydroceramide (DhCer), ceramide (Cer), sphingosine-1-phosphate (S1P), sphingomyelin (SM), lactosylceramide (LacCer), and glucosylceramide (GluCer) in carotid plaques, and demonstrated their potential as inducers of plaque inflammation. In this review, we point out their specific roles in atherosclerosis by focusing on different cell types, carrier molecules, enzymes, and receptors involved in atherogenesis. Whereas we assume mainly atheroprotective effects for GluCer and LacCer, the sphingolipids DhCer, Cer, SM and S1P mediate chimeric functions. Initial studies demonstrate the successful use of interventions in the sphingolipid pathway to prevent atherosclerosis. However, as atherosclerosis is a multifactorial disease with a variety of underlying cellular processes, it is imperative for future research to emphasize the circumstances in which sphingolipids exert protective or progressive functions and to evaluate their therapeutic benefits in a spatiotemporal manner.

From In Vitro to Perioperative Vascular Tissue Engineering: Shortening Production Time by Traceable Textile-Reinforcement

Background:The production of tissue-engineered vascular graft (TEVG) usually involves a prolonged bioreactor cultivation period of up to several weeks to achieve maturation of extracellular matrix and sufficient mechanical strength. Therefore, we aimed to substantially shorten this conditioning time by combining a TEVG textile scaffold with a recently developed copolymer reinforced fibrin gel as a cell carrier. We further implemented our grafts with magnetic resonance imaging (MRI) contrast agents to allow the in-vitro monitoring of the TEVG’s remodeling process.Methods:Biodegradable polylactic-co-glycolic acid (PLGA) was electrospun onto a non-degradable polyvinylidene fluoride scaffold and molded along with copolymer-reinforced fibrin hydrogel and human arterial cells. Mechanical tests on the TEVGs were performed both instantly after molding and 4 days of bioreactor conditioning. The non-invasive in vitro monitoring of the PLGA degradation and the novel imaging of fluorinated thermoplastic polyurethane (19F-TPU) were performed using 7T MRI.Results:After 4 days of close loop bioreactor conditioning, 617 ± 85 mmHg of burst pressure was achieved, and advanced maturation of extracellular matrix (ECM) was observed by immunohistology, especially in regards to collagen and smooth muscle actin. The suture retention strength (2.24 ± 0.3 N) and axial tensile strength (2.45 ± 0.58 MPa) of the TEVGs achieved higher values than the native arteries used as control. The contrast agents labeling of the TEVGs allowed the monitorability of the PLGA degradation and enabled the visibility of the non-degradable textile component.Conclusion:Here, we present a concept for a novel textile-reinforced TEVG, which is successfully produced in 4 days of bioreactor conditioning, characterized by increased ECM maturation and sufficient mechanical strength. Additionally, the combination of our approach with non-invasive imaging provides further insights into TEVG’s clinical application.

Mitochondrial neurogastrointestinal encephalomyopathy in a Pakistani female: a case report

BackgroundMitochondrial neurogastrointestinal encephalopathy is a rare multisystem autosomal recessive disease caused by mutations in the TYMP gene, that encodes for thymidine phosphorylase. Mitochondrial neurogastrointestinal encephalopathy is a progressive degenerative disease characterized by a distinctive tetrad of gastrointestinal dysmotility, peripheral neuropathy, ophthalmoplegia with ptosis, and asymptomatic leukoencephalopathy. It provides a diagnostic dilemma to physicians in regions like Pakistan because of a lack of genetic study availability and associated financial constraints of the population. However, with careful examination and a few basic investigations, mitochondrial neurogastrointestinal encephalopathy can be diagnosed by ruling out most of the close differentials.Case presentationWe report the case of a 23-year-old Asian female whose chief complaints were epigastric pain, bilious emesis, weight loss for 3 months, and bilateral lower limb weakness for 20 days. All clinical signs and symptoms along with relevant investigations including nerve conduction studies, electromyography, and magnetic resonance imaging of the brain were highly suggestive of mitochondrial neurogastrointestinal encephalopathy syndrome. Because of financial constraints, genetic studies could not be performed. The patient was managed with a multidisciplinary approach involving gastroenterology, physiotherapy, and nutrition departments. Currently, therapeutic options for the disease include allogeneic hematopoietic stem cell transplant and carrier erythrocyte entrapped thymidine phosphorylase; however, these could not be provided to the patient owing to certain limitations.ConclusionsAs misdiagnosis and delayed diagnosis are quite common in this disease, the prime objective of this case report is to increase the basic understanding of this disease, especially its signs and symptoms, and address the limitations regarding the diagnostic investigations and management of patients with mitochondrial neurogastrointestinal encephalopathy.

Leukocyte-nanomedicine system for targeted delivery and precise theragnostics

Targeted delivery of nanomedicines to disease sites via living cell carriers has attracted extensive attention, but a better way to direct nanomedicines to carriers is still under exploration. Recently in <i>Nature Nanotechnology</i>, Cruz et al. modified the binding peptides on nanomedicines to hitchhike with specifically activated leukocytes for improved therapy of venous thrombosis.

A review of polysaccharide based hydrogel as cell carrier in wound healing

Various types of wound treatment materials have been developed that influenced by numerous wound types and wound management using hydrogel has been explored and widely used before. Among current strategies of development of hydrogel is the one that can act as a cell carrier that is applicable for wound healing. Thus, this study is conducted for reviewing the synthesis and method approaches for various polysaccharide-based hydrogel as wound healing materials. In other hand, this study is concerning on properties of hydrogel and their biological role as cell carrier that can support wound healing process by reviewing studies that related to polysaccharide-based hydrogel as cell carrier. Various types of polysaccharide-based hydrogel such as alginate, chitosan and hyaluronic acid have been developed using different type of approaches for wound healing. They can capsulate various type of cells that and the formed polymers give an excellent support for the cells such as to be delivered to the host tissues as well as aiding angiogenesis to accelerate wound healing. The emerging polysaccharide-based hydrogel for wound carrier has a very promising criterion that can be polished further due to its favorable qualities in assisting wound healing mechanisms.

Influence of the Components and Orientation of Hydroxyapatite Fibrous Substrates on Osteoblast Behavior.

Synthetic hydroxyapatite has good biocompatibility, bioactivity and osteoconductive ability because its chemical properties and biological properties are similar to those of bioapatite in bone tissue. Strontium-substituted hydroxyapatite has better degradability than hydroxyapatite and can both promote osteogenesis and inhibit adipogenesis in mesenchymal stem cells. Hence, hydroxyapatite and strontium-substituted hydroxyapatite are widely used as bone graft materials, cell carriers and drug/gene delivery carriers. In addition, osteoblasts cultured on aligned nanofibrous substrates had higher expression of osteogenesis-related genes than did those cultured on random nanofibrous substrates. However, to date, no study has explored the effects of the components and orientation of hydroxyapatite nanofibrous substrates on osteoblastic behavior. In this study, a random hydroxyapatite nanofibrous substrate (R-HANF), a random strontium-substituted hydroxyapatite nanofibrous substrate (R-SrHANF), an aligned hydroxyapatite nanofibrous substrate (A-HANF) and an aligned strontium-substituted hydroxyapatite nanofibrous substrate (A-SrHANF) were successfully fabricated by using the electrospinning technique. The effect of fiber composition on osteoblast-like MG63 cells was assessed by evaluating cell morphology, cell proliferation and osteogenesis-related gene expression. The results showed that MG63 cells cultured on A-SrHANF had higher osteogenesis-related gene expression than those cultured on A-HANF. Additionally, MG63 cells were cultured on R-SrHANF and A-SrHANF to evaluate the effects of fiber orientation on cell behavior. On A-SrHANF, the cells aligned along the direction of the nanofibers, with typical bipolar morphologies, and exhibited higher osteogenesis-related gene expression than cells on R-SrHANF. Hence, the components and orientation of hydroxyapatite nanofibrous substrates are critical parameters affecting the osteogenesis process.

STAC3 determines the slow activation kinetics of CaV 1.1 currents and inhibits its voltage-dependent inactivation.

The skeletal muscle CaV 1.1 channel functions as the voltage-sensor of excitation-contraction (EC) coupling. Recently, the adaptor protein STAC3 was found to be essential for both CaV 1.1 functional expression and EC coupling. Interestingly, STAC proteins were also reported to inhibit calcium-dependent inactivation (CDI) of L-typecalcium channels (LTCC), an important negative feedback mechanism in calcium signaling. The same could not be demonstrated for CaV 1.1, as STAC3 is required for its functional expression. However, upon strong membrane depolarization, CaV 1.1 conducts calcium currents characterized by very slow kinetics of activation and inactivation. Therefore, we hypothesized that the negligible inactivation observed in CaV 1.1 currents reflects the inhibitory effect of STAC3. Here, we inserted a triple mutation in the linker region of STAC3 (ETLAAA), as the analogous mutation abolished the inhibitory effect of STAC2 on CDI of CaV 1.3 currents. When coexpressed in CaV 1.1/STAC3 double knockout myotubes, the mutant STAC3-ETLAAA failed to colocalize with CaV 1.1 in the sarcoplasmic reticulum/membrane junctions. However, combined patch-clamp and calcium recording experiments revealed that STAC3-ETLAAA supports CaV 1.1 functional expression and EC coupling, although at a reduced extent compared to wild-type STAC3. Importantly, STAC3-ETLAAA coexpression dramatically accelerated the kinetics of activation and inactivation of CaV 1.1 currents, suggesting that STAC3 determines the slow CaV 1.1 currents kinetics. To examine if STAC3 specifically inhibits the CDI of CaV 1.1 currents, we performed patch-clamp recordings using calcium and barium as charge carriers in HEK cells. While CaV 1.1 displayed negligible CDI with STAC3, this did not increase in the presence of STAC3-ETLAAA. On the contrary, our data demonstrate that STAC3 specifically inhibits the voltage-dependent inactivation (VDI) of CaV 1.1 currents. Altogether, these results designate STAC3 as a crucial determinant for the slow activation kinetics of CaV 1.1 currents and implicate STAC proteins as modulators of both components of inactivation of LTCC.

The Hollow Porous Sphere Cell Carrier for the Dynamic Three-Dimensional Cell Culture.

Large-scale mammalian cell culture is essential in cell therapy, vaccine production, and the manufacturing of therapeutic protein drugs. Due to the adherent growth characteristic of most mammalian cell types, the combination of cell carrier and bioreactor is a common choice in large-scale mammalian cell culture. Current cell carriers developed by polymer crosslinking, lithography, or emulsion drops are unable to obtain a structure with uniformed porous structure and porous interior design, which results in an inhomogeneous culture condition for cells and therefore cannot ensure an optimal dynamic culture condition for cell proliferation, matrix production, and cell differentiation. In addition, the fluidic shear stress (a standard mechanical stimulation in bioreactor culture) and inner-carrier velocity (to ensure nutrient transport and waste exchange), which influence cell viability and growth, are not well-controlled/analyzed due to an irregular porous structure with these traditionally synthesized cell carriers. To solve these problems, we designed four types of hollow porous spheres (HPS, 1.0 cm diameter) with different porous structures. To investigate the impacts of porous structure on surface shear stress and inner velocity, computational fluid dynamics (CFD) simulations were conducted to analyze the liquid flow behavior in HPSs, based on which an optimal structure with minimal surface shear stress and best inner velocity was obtained and fabricated using fused deposition modeling three-dimensional (3D) printing technology. Inspired by the industrial large-scale culture system, a novel 3D dynamic culture system was then established using HPSs to seed the cells, which were then placed in a mini bioreactor on a tube roller. CFD analysis showed that under 0.1 m/s water flow, the shear stress at most surface areas from four HPSs was lower than 20 dynes/cm2, which suggests that the HPSs should provide protection against physical stress to the cells living on the scaffold surface. A dynamic cell seeding was developed and refined using the 3D culture system, which increased the 32% seeding efficiency of MC3T3 cells compared to the traditional static cell seeding method. The cell proliferation analysis demonstrated that HPSs could speed up cell growth in dynamic cell culture. The HPS with a honeycomb-like structure showed the highest inner pore velocity (CFD analysis) and achieved the fastest cell proliferation and the highest cell viability. Overall, our study, for the first time, developed a 3D printed HPS cell culture device with a uniformed porous structure, which can effectively facilitate cell adhesion and proliferation in the dynamic cultural environment, thereby could be considered an ideal carrier candidate.

An Alternative Approach to Improve the Butanol Production Efficiency from Sweet Sorghum Stem Juice Using Immobilized Cells Combined with an In Situ Gas Stripping System

The effects of the nitrogen source and buffers used in butanol production with Clostridium beijerinckii TISTR 1461 from sweet sorghum stem juice (SSJ) containing 60 g/L of total sugar were first studied in this paper. Among the various nitrogen sources (dried spent yeast, urea, ammonium acetate, ammonium sulfate), urea was found to be the most suitable for butanol production. SSJ supplemented with urea (0.64 g/L) and cocktail buffers (KH2PO4, 0.5 g/L; K2HPO4, 0.5 g/L; ammonium acetate, 2.2 g/L) gave the highest butanol concentration (PB, 10.13 g/L). Then, the capability of immobilized C. beijerinckii TISTR 1461 cells for butanol fermentation was investigated. Two residual waste materials were examined as immobilized cell carriers. Bamboo chopstick pieces were more appropriate as carriers for cell immobilization than cigarette filter tips. The PB value of the immobilized cells on the bamboo chopstick pieces was ~13% higher than that on the cigarette filter tips. Using the response surface methodology (RSM), 1.9 cm bamboo chopstick pieces with a carrier loading of 1:32 (w/v) were the optimum conditions for cell immobilization for butanol production. Under these conditions, the PB value was 11.62 g/L. To improve the butanol production efficiency, a gas stripping system (GS) was connected to the fermenter. It was found that the PB (14.02 g/L) and butanol productivity (QB, 0.29 g/L·h) values improved by ~21% compared to butanol fermentation using no gas stripping.

Lactic Acid Bacteria Simultaneously Encapsulate Diverse Bioactive Compounds from a Fruit Extract and Enhance Thermal Stability.

This study develops an innovative cell-based carrier to simultaneously encapsulate multiple phytochemicals from a complex plant source. Muscadine grapes (MG) juice prepared from fresh fruit was used as a model juice. After incubation with inactivated bacterial cells, 66.97% of the total anthocyanins, and 72.67% of the total antioxidant compounds were encapsulated in the cells from MG juice. Confocal images illustrated a uniform localization of the encapsulated material in the cells. The spectral emission scans indicated the presence of a diverse class of phenolic compounds, which was characterized using high-performance liquid chromatography (HPLC). Using HPLC, diverse phytochemical compound classes were analyzed, including flavanols, phenolic acid, hydroxycinnamic acid, flavonols, and polymeric polyphenols. The analysis validated that the cell carrier could encapsulate a complex profile of bioactive compounds from fruit juice, and the encapsulated content and efficiencies varied by the chemical class and compound. In addition, after the heat treatment at 90 °C for 60 min, >87% total antioxidant capacity and 90% anthocyanin content were recovered from the encapsulated MG. In summary, these results highlight the significant potential of a selected bacterial strain for simultaneous encapsulation of diverse phenolic compounds from fruit juice and improving their process stability.

A supramolecular injectable hydrogel based on β-cyclodextrin-grafted alginate and pluronic-amine loaded with kartogenin for chondrogenic differentiation of mesenchymal stem cells

Owing to the similarity of hydrogels to cartilage extracellular matrix, they have been extensively utilized in the chondral lesions. Moreover, their tunable administration properties are desirable for reducing injuries in lesion sites. Generally, injectable hydrogels are mechanically weak, requiring some modifications for being used as a cell carrier in place of articular cartilage. In this study, a combination of β-cyclodextrin-grafted alginate (Alg-β-CD) and pluronic-amine with multiple physical crosslinking was used for the first time. Supramolecular interactions, including electrostatic forces, host-guest interaction, and hydrophobic interaction with increasing temperature maintain injectability of hydrogels while these interactions boost mechanical properties to the extent that shear modulus surpassed 40 kPa. Vacant β-CD cavities in conjunction with gel network were exploited for kartogenin (KGN) loading. All groups had gel time of less than one minute and gel temperature was 28 °C. No toxic effect of hydrogels on encapsulated cells was observed. While the optimum combination of polymers provided a sustainable release for KGN, it also extended the in vitro degradation time of hydrogels from six days to two weeks. KGN facilitated encapsulated mesenchymal stem cells differentiation towards chondrocytes. Taken together, the synthesized hydrogel proved to be a promising candidate for being utilized in cartilage regeneration.

A dopamine-methacrylated hyaluronic acid hydrogel as an effective carrier for stem cells in skin regeneration therapy

Adipose-derived stem cells (ADSCs) show potential in skin regeneration research. A previous study reported the failure of full-thickness skin self-repair in an injury area exceeding 4 cm in diameter. Stem cell therapies have shown promise in accelerating skin regeneration; however, the low survival rate of transplanted cells due to the lack of protection during and after transplantation leads to low efficacy. Hence, effective biomaterials for the delivery and retention of ADSCs are urgently needed for skin regeneration purposes. Here, we covalently crosslinked hyaluronic acid with methacrylic anhydride and then covalently crosslinked the product with dopamine to engineer dopamine-methacrylated hyaluronic acid (DA-MeHA). Our experiments suggested that the DA-MeHA hydrogel firmly adhered to the skin wound defect and promoted cell proliferation in vitro and skin defect regeneration in vivo. Mechanistic analyses revealed that the beneficial effect of the DA-MeHA hydrogel combined with ADSCs on skin defect repair may be closely related to the Notch signaling pathway. The ADSCs from the DA-MeHA hydrogel secrete high levels of growth factors and are thus highly efficacious for promoting skin wound healing. This DA-MeHA hydrogel may be used as an effective potential carrier for stem cells as it enhances the efficacy of ADSCs in skin regeneration.

Physical and Natural Crosslinking Approaches on Three-Dimensional Gelatin Microspheres for Cartilage Regeneration.

The use of gelatin microspheres (GMs) as a cell carrier has been extensively researched. One of its limitations is that it dissolves rapidly in aqueous settings, precluding its use for long-term cell propagation. This circumstance necessitates the use of crosslinking agents to circumvent the constraint. Thus, this study examines two different methods of crosslinking and their effect on the microsphere's physicochemical and cartilage tissue regeneration capacity. Crosslinking was accomplished by physical (dehydrothermal [DHT]) and natural (genipin) crosslinking of the three-dimensional (3D) GM. We begin by comparing the microstructures of the scaffolds and their long-term resistance to degradation under physiological conditions (in an isotonic solution, at 37°C, pH = 7.4). Infrared spectroscopy indicated that the gelatin structure was preserved after the crosslinking treatments. The crosslinked GM demonstrated good cell adhesion, viability, proliferation, and widespread 3D scaffold colonization when seeded with human bone marrow mesenchymal stem cells. In addition, the crosslinked microspheres enhanced chondrogenesis, as demonstrated by the data. It was discovered that crosslinked GM increased the expression of cartilage-related genes and the biosynthesis of a glycosaminoglycan-positive matrix as compared with non-crosslinked GM. In comparison, DHT-crosslinked results were significantly enhanced. To summarize, DHT treatment was found to be a superior approach for crosslinking the GM to promote better cartilage tissue regeneration.

An Insight into the Role of Marine Biopolymer Alginate in Endodontics: A Review

Alginate is a natural marine biopolymer that has been widely used in biomedical applications, but research on its use as an endodontic material is still sparse in the literature. This pioneer review aims to summarize the emerging roles of alginate and to outline its prospective applications as a core biomaterial in endodontics. Ten electronic databases and five textbooks were used to perform a search of English-language literature on the use of alginate in endodontics published between January 1980 and June 2022. The risk of bias (RoB) of each included study was assessed using the Office of Health Assessment and Translation (OHAT) tool. Subsequently, studies were categorized into three tiers to represent the overall risk. Qualitative analysis was performed, and the articles were sorted into different thematic categories. An initial search yielded a total of 1491 articles, but only 13 articles were chosen. For most domains, all the studies were rated with ‘probably low’ or ‘definitely low’ RoB, except for domains 2 and 6. All included studies fall in the Tier 1 category and were either in vitro, in vivo, or ex vivo. Four thematic categories were identified: endodontic regeneration, intracanal medicament, filing material, and chelating agent. Based on the available evidence, alginate has emerged as a cell carrier and scaffold in regenerative endodontics, a microcapsule delivery system for intracanal medicaments, a chelating agent reinforcing material, and a root canal sealer. More well-designed experiments and clinical trials are needed to warrant the promising advent of this hydrogel-based biomaterial.

Injectable conductive micro-cryogel as a muscle stem cell carrier improves myogenic proliferation, differentiation and in situ skeletal muscle regeneration

Volumetric muscle loss (VML) results in the impediment of skeletal muscle function, and there were still great challenges in cell delivery approach with the minimally invasive operation to repair muscle defects. To deliver cells to the VML defects site efficiently, the injectable conductive porous nanocomposite microcryogels based on gelatin (GT) and reduced graphene oxide (rGO) were designed and prepared. The microcryogels were loaded with myoblasts to form an injectable cell delivery system and show the ability to protect cells during injection. Conductive microcryogel with 4 mg/mL rGO (GT/rGO4) enhanced C2C12 cell proliferation and myogenic differentiation during 3D culture compared with pure gelatin microcryogel. In a mice VML model, injection of microcryogel loaded with muscle-derived stem cells into the injury site significantly improved the generation of new muscle fibers and blood vessels, and anti-inflammatory properties. The results show that injectable biodegradable conductive microcryogel can be used as muscle stem cell carriers with the potential to maintain cell activity and deliver cells to defective sites, thereby in situ enhancing skeletal muscle regeneration. Statement of significanceVolumetric muscle loss overwhelms the regenerative capacity of skeletal muscle, which results in severe damage to muscle tissues. In the treatment of volumetric muscle loss, conductive niche and muscle stem cells are needed to alleviate excessive scar formation and inflammation to improve muscle regeneration. Injectable gelatin/reduced graphene oxide based nanocomposite microcryogel can enhance the differentiation of seeded muscle stem cells. The improved repair of volumetric muscle loss was achieved via reducing collagen deposition and inflammation in the injected region through the microcryogel cell-delivery therapy, suggesting great potential of the injectable microcryogel as a cell carrier in soft tissue repair.

Quantitative and Qualitative Changes in the Genetic Diversity of Bacterial Communities in Anaerobic Bioreactors with the Diatomaceous Earth/Peat Cell Carrier.

This paper analyses the impact of the diatomaceous earth/peat (DEP; 3:1) microbial carrier on changes in the bacterial microbiome and the development of biofilm in the anaerobic digestion (AD) of confectionery waste, combined with digested sewage sludge as inoculum. The physicochemical properties of the carrier material are presented, with particular focus on its morphological and dispersion characteristics, as well as adsorption and thermal properties. In this respect, the DEP system was found to be a suitable carrier for both mesophilic and thermophilic AD. The evaluation of quantitative and qualitative changes in the genetic diversity of bacterial communities, carried out using next-generation sequencing (NGS), showed that the material has a modifying effect on the bacterial microbiome. While Actinobacteria was the most abundant cluster in the WF-control sample (WF—waste wafers), Firmicutes was the dominant cluster in the digested samples without the carrier (WF-dig.; dig.—digested) and with the carrier (WF + DEP). The same was true for the count of Proteobacteria, which decreased twofold during biodegradation in favor of Synergistetes. The Syntrophomonas cluster was identified as the most abundant genus in the two samples, particularly in WF + DEP. This information was supplemented by observations of morphological features of microorganisms carried out using fluorescence microscopy. The biodegradation process itself had a significant impact on changes in the microbiome of samples taken from anaerobic bioreactors, reducing its biodiversity. As demonstrated by the results of this innovative method, namely the BioFlux microfluidic flow system, the decrease in the number of taxa in the digested samples and the addition of DEP contributed to the microbial adhesion in the microfluidic system and the formation of a stable biofilm.