Multimodal treatment combining cold atmospheric plasma and acidic fibroblast growth factor for multi-tissue regeneration.

Cold atmospheric plasma (CAP) is an emerging technology for biomedical applications, exemplified by its antimicrobial and antineoplastic potentials. On the contrary, acidic fibroblast growth factor (aFGF) has been a long-standing potent mitogen for cells from various origins. In this study, we are the first to develop a multimodal treatment combining the aforementioned physicochemical and pharmacological treatments and investigated their individual and combined effects on wound healing, angiogenesis, neurogenesis, and osteogenesis.

Cold atmospheric plasma as an interface biotechnology for enhancing surgical implants.

Cold atmospheric plasma (CAP) has been intensively researched for direct treatment of living cells and tissues. Significant attention is now being given to its indirect applications in plasma medicine. Surgical implant is an exemplary conveyor to deliver the therapeutic effects of plasma to patients.

Controlling stem cell fate using cold atmospheric plasma.

The stem cell is the foundation of regenerative medicine and tissue engineering. Regulating specific stem cell fate, such as cell attachment, proliferation, differentiation, and even death, undergoes continuous development. Cold atmospheric plasma (CAP), the core technology of plasma medicine, is attracting tremendous attention due to its ability and versatility to manipulate various types of cells, including stem cells.

Recent advances in the implant-based drug delivery in otorhinolaryngology.

The surgical implant is an interdisciplinary therapeutic modality that offers unique advantages in the daily practice of otorhinolaryngology. Some well-known examples include cochlear implants, bone-anchored hearing aids, sinus stents, and tracheostomy tubes. Neuroprotective, osteogenic, anti-inflammatory, and antimicrobial effects are among their established or pursued functions.

A multifunctional dexamethasone-delivery implant fabricated using atmospheric plasma and its effects on apoptosis, osteogenesis and inflammation.

Implant-based local drug delivery is a unique surgical therapy with many clinical advantages. Atmospheric pressure plasma is a novel non-thermal surface biotechnology that has only recently been applied in enhancing a surgical implant. We are the first to use this technology to successfully create a dexamethasone-delivery metallic implant.

Customizable Implant-specific and Tissue-Specific Extracellular Matrix Protein Coatings Fabricated Using Atmospheric Plasma.

Progression in implant science has benefited from ample amount of technological contributions from various disciplines, including surface biotechnology. In this work, we successfully used atmospheric plasma to enhance the biological functions of surgical implants by coating them with extracellular matrix proteins. The developed collagen and laminin coatings demonstrate advantageous material properties.

Physiological alterations of GS-CHO cells in response to adenosine monophosphate treatment.

Growth-arrested strategies (e.g. hypothermia and hyperosmolarity) have been widely employed to enhance cell-specific productivity (qP) in mammalian cell culture bioprocess.

Surface-enhanced Raman scattering for rapid hematopoietic stem cell differentiation analysis.

Raman-spectroscopy-based methods, such as surface-enhanced Raman spectroscopy, are a well-evolved method to molecular fingerprint cell types. Here we demonstrate that surface-enhanced Raman spectroscopy can enable us to distinguish cell development stages of bone marrow hematopoietic stem cells towards red blood cells through the identification of specific surface-enhanced Raman spectroscopy biomarkers. The approach taken here is to allow cells to take in gold nanoparticles as Raman enhancement platforms for kinetic structural observations presented here through the view of the multidimensional parameter contribution, thereby enabling profiling of bone marrow hematopoietic stem cells acquired from proliferation (stage one), differentiation (stage two), and mature red blood cells (stage three).

The relationship of metabolic burden to productivity levels in CHO cell lines.

The growing demand for recombinant therapeutics has driven biotechnologists to develop new production strategies. One such strategy for increasing the expression of heterologous proteins has focused on enhancing cell-specific productivity through environmental perturbations. In this work, the effects of hypothermia, hyperosmolarity, high shear stress, and sodium butyrate treatment on growth and productivity were studied using three (low, medium, and high producing) CHO cell lines that differed in their specific productivities of monoclonal antibody.

3D culture of mouse gastric stem cells using porous microcarriers.

The lining epithelium of the stomach includes multipotent stem cells which undergo proliferation and migration-associated differentiation. These cells give rise to multiple cell lineages that produce mucus, acid, pepsinogen and various hormones/peptides. A 3D culture for stem cells would facilitate identification of the factors that control proliferation and/or differentiation programs.

Understanding central carbon metabolism of rapidly proliferating mammalian cells based on analysis of key enzymatic activities in GS-CHO cell lines.

The central carbon metabolism (glycolysis, the pentose phosphate pathway [PPP], and the tricarboxylic acid [TCA] cycle) plays an essential role in the supply of biosynthetic precursors and energy. How the central carbon metabolism changes with the varying growth rates in the in vitro cultivation of rapidly proliferating mammalian cells, such as cancer cells and continuous cell lines for recombinant protein production, remains elusive. Based on relationships between the growth rate and the activity of seven key enzymes from six cell clones, this work reports finding an important metabolic characteristic in rapidly proliferating glutamine synthetase-Chinese hamster ovary cells.

Verhulst and stochastic models for comparing mechanisms of MAb productivity in six CHO cell lines.

The present study validates previously published methodologies-stochastic and Verhulst-for modelling the growth and MAb productivity of six CHO cell lines grown in batch cultures. Cytometric and biochemical data were used to model growth and productivity. The stochastic explanatory models were developed to improve our understanding of the underlying mechanisms of growth and productivity, whereas the Verhulst mechanistic models were developed for their predictability.

Revisiting Verhulst and Monod models: analysis of batch and fed-batch cultures.

The paper re-evaluates Verhulst and Monod models. It has been claimed that standard logistic equation cannot describe the decline phase of mammalian cells in batch and fed-batch cultures and in some cases it fails to fit somatic growth data. In the present work Verhulst, population-based mechanistic growth model was revisited to describe successfully viable cell density (VCD) in exponential and decline phases of batch and fed-batch cultures of three different CHO cell lines.

Online flow cytometry for monitoring apoptosis in mammalian cell cultures as an application for process analytical technology.

Apoptosis is the main driver of cell death in bioreactor suspension cell cultures during the production of biopharmaceuticals from animal cell lines. It is known that apoptosis also has an effect on the quality and quantity of the expressed recombinant protein. This has raised the importance of studying apoptosis for implementing culture optimization strategies.

The relationship between mTOR signalling pathway and recombinant antibody productivity in CHO cell lines.

Background: High recombinant protein productivity in mammalian cell lines is often associated with phenotypic changes in protein content, energy metabolism, and cell growth, but the key determinants that regulate productivity are still not clearly understood. The mammalian target of rapamycin (mTOR) signalling pathway has emerged as a central regulator for many cellular processes including cell growth, apoptosis, metabolism, and protein synthesis. This role of this pathway changes in response to diverse environmental cues and allows the upstream proteins that respond directly to extracellular signals (such as nutrient availability, energy status, and physical stresses) to communicate with downstream effectors which, in turn, regulate various essential cellular processes.

Surface biotechnology for refining cochlear implants.

The advent of the cochlear implant is phenomenal because it is the first surgical prosthesis that is capable of restoring one of the senses. The subsequent rapid evolution of cochlear implants through increasing complexity and functionality has been synchronized with the recent advancements in biotechnology. Surface biotechnology has refined cochlear implants by directly influencing the implant–tissue interface.

Quantifying nanoscale biochemical heterogeneity in human epithelial cancer cells using combined AFM and PTIR absorption nanoimaging.

Subcellular chemical heterogeneity plays a key role in cell organization and function. However the biomechanics underlying the structure-function relationship is governed by cell substructures which are poorly resolved using conventional chemical imaging methods. To date, advances in sub-diffraction limited infrared (IR) nanoscopy have permitted intracellular chemical mapping.

Using molecular markers to characterize productivity in Chinese hamster ovary cell lines.

Selection of high producing cell lines to produce maximum product concentration is a challenging and time consuming task for the biopharmaceutical industry. The identification of early markers to predict high productivity will significantly reduce the time required for new cell line development. This study identifies candidate determinants of high productivity by profiling the molecular and morphological characteristics of a panel of six Chinese Hamster Ovary (CHO) stable cell lines with varying recombinant monoclonal antibody productivity levels ranging between 2 and 50 pg/cell/day.

Enhancement of monoclonal antibody production in CHO cells by exposure to He-Ne laser radiation.

This study tested the effectiveness of laser biostimulation in small-scale cultures in vitro. We investigated the response of recombinant CHO cells, which are used for the production of monoclonal antibody, to low level laser radiation. The cells were irradiated using a 632.

Application of statistical techniques for elucidating flow cytometric data of batch and fed-batch cultures.

The objective of this work is to develop structured, segregated stochastic models for bioprocesses using time-series flow cytometric (FC) data. To this end, mammalian CHO cells were grown in both batch and fed-batch cultures, and their viable cell numbers (VCDs), monoclonal antibody (MAb), cell cycle phases, mitochondria membrane potential/mitochondria mass, Golgi apparatus, and endoplasmic reticulum (ER) were analyzed. For the fed-batch mode, soy hydrolysate was introduced at 24-H intervals.

Growth, metabolic activity, and productivity of immobilized and freely suspended CHO cells in perfusion culture.

Chinese hamster ovary (CHO) cells producing β-galactosidase (β-gal) were successfully cultured on silicone-based porous microcarriers (ImmobaSil FS) in a 1 L stirred-tank perfusion bioreactor. We studied the growth, metabolism, and productivity of free and immobilized cells to understand cellular activity in immobilized conditions. CHO cells attached to ImmobaSil FS significantly better than to other microcarriers.

Mathematical approach for the optimal expansion of erythroid progenitors in monolayer culture.

The continuous production of large numbers of red blood cells (RBCs) ex vivo is a challenging task due to process economics and complex culture conditions. In any serial passaging process, the culture conditions and operation mode are important criteria for achieving high proliferation with optimal passage lengths. The optimal inoculation concentration for serial passaging is a factor that affects both the kinetics and the total expansion performance.