Poly(Lactic-Co-Glycolic Acid) Microparticles for the Delivery of Model Drug Compounds for Applications in Vascular Tissue Engineering.

Introduction: Localized delivery of angiogenesis-promoting factors such as small molecules, nucleic acids, peptides, and proteins to promote the repair and regeneration of damaged tissues remains a challenge in vascular tissue engineering. Current delivery methods such as direct administration of therapeutics can fail to maintain the necessary sustained release profile and often rely on supraphysiologic doses to achieve the desired therapeutic effect. By implementing a microparticle delivery system, localized delivery can be coupled with sustained and controlled release to mitigate the risks involved with the high dosages currently required from direct therapeutic administration.

Granular PEG hydrogels mediate osteoporotic MSC clustering via N-cadherin influencing the pro-resorptive bias of their secretory profile.

Postmenopausal osteoporosis results from a pro-resorptive bone environment, which decreases bone mineral density causing increased fracture risk. Bone marrow derived mesenchymal stem/stromal cells (MSCs) secrete factors involved in bone homeostasis, but osteoporosis mediated changes to their secretions remain understudied. Herein, we examined the secretome of MSCs isolated from ovariectomized rats (OVX rMSCs), a model of post-menopausal osteoporosis, as a function of cell-cell interactions.

Advanced biomedical hydrogels: molecular architecture and its impact on medical applications.

Hydrogels are cross-linked polymeric networks swollen in water, physiological aqueous solutions or biological fluids. They are synthesized by a wide range of polymerization methods that allow for the introduction of linear and branched units with specific molecular characteristics. In addition, they can be tuned to exhibit desirable chemical characteristics including hydrophilicity or hydrophobicity.

Electrostatic and Covalent Assemblies of Anionic Hydrogel-Coated Gold Nanoshells for Detection of Dry Eye Biomarkers in Human Tears.

Although dry eye is highly prevalent, many challenges exist in diagnosing the symptom and related diseases. For this reason, anionic hydrogel-coated gold nanoshells (AuNSs) were used in the development of a label-free biosensor for detection of high isoelectric point tear biomarkers associated with dry eye. A custom, aldehyde-functionalized oligo(ethylene glycol)acrylate (Al-OEGA) was included in the hydrogel coating to enhance protein recognition through the formation of dynamic covalent (DC) imine bonds with solvent-accessible lysine residues present on the surface of select tear proteins.

Recent Advancements in Biosensing Approaches for Screening and Diagnostic Applications.

Recent advancements in molecular recognition have provided additional diagnostic and treatment approaches for multiple diseases, including autoimmune disorders and cancers. Research investigating how the composition of biological fluids is altered during disease progression, including differences in the expression of the small molecules, proteins, RNAs, and other components present in patient tears, saliva, blood, urine, or other fluids, has provided a wealth of potential candidates for early disease screening; however, adoption of biomarker screening into clinical settings has been challenged by the need for more robust, low-cost, and high-throughput assays. This review examines current approaches in molecular recognition and biosensing for the quantification of biomarkers for disease screening and diagnostic outcomes.

Lipid- and Polymer-Based Nanoparticle Systems for the Delivery of CRISPR/Cas9.

The discovery of clustered regularly interspaced short palindromic repeat (CRISPR)/ CRISPR-associated (Cas) genome editing systems and their applications in human health and medicine has heralded a new era of biotechnology. However, the delivery of CRISPR therapeutics is arguably the most difficult barrier to overcome for translation to clinical administration. Appropriate delivery methods are required to efficiently and selectively transport all gene editing components to specific target cells and tissues of interest, while minimizing off-target effects.

Engineering the MSC Secretome: A Hydrogel Focused Approach.

The therapeutic benefits of exogenously delivered mesenchymal stromal/stem cells (MSCs) have been largely attributed to their secretory properties. However, clinical translation of MSC-based therapies is hindered due to loss of MSC regenerative properties during large-scale expansion and low survival/retention post-delivery. These limitations might be overcome by designing hydrogel culture platforms to modulate the MSC microenvironment.

Charged Poly(-isopropylacrylamide) Nanogels for the Stabilization of High Isoelectric Point Proteins.

Storage and transportation of protein therapeutics using refrigeration is a costly process; a reliable electrical supply is vital, expensive equipment is needed, and unique transportation is required. Reducing the reliance on the cold chain would enable low-cost transportation and storage of biologics, ultimately improving accessibility of this class of therapeutics to patients in remote locations. Herein, we report on the synthesis of charged poly(-isopropylacrylamide) nanogels that efficiently adsorb a range of different proteins of varying isoelectric points and molecular weights (e.

Engineering precision nanoparticles for drug delivery.

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy.

Nanogel receptors for high isoelectric point protein detection: influence of electrostatic and covalent polymer-protein interactions.

An aldehyde acrylate-based functional monomer was incorporated into poly(N-isopropylacrylamide-co-methacrylic acid) nanogels for use as protein receptors. The aldehyde component forms dynamic imines with surface exposed lysine residues, while carboxylic acid/carboxylate moieties form electrostatic interactions with high isoelectric point proteins. Together, these interactions effect protein adsorption and recognition.

Developing a Multidisciplinary Approach for Engineering Stem Cell Organoids.

Recent advances in stem cell biology, synthetic biology, bioengineering, and biotechnology have included significant work leading to the development of stem cell-derived organoids. The growing popularity of organoid research and use of organoids is widely due to the fact that these three-dimensional cellular structures better model human physiology compared to traditional in vitro and in vivo methods by recapitulating many biologically relevant parameters. Organoids show great promise for a wide range of applications, such as for use in disease modeling, drug discovery, and regenerative medicine.

Engineered microscale hydrogels for drug delivery, cell therapy, and sequencing.

Engineered microscale hydrogels have emerged as promising therapeutic approaches for the treatment of various diseases. These microgels find wide application in the biomedical field because of the ease of injectability, controlled release of therapeutics, flexible means of synthesis, associated tunability, and can be engineered as stimuli-responsive. While bulk hydrogels of several length-scale dimensions have been used for over two decades in drug delivery applications, their use as microscale carriers of drug and cell-based therapies is relatively new.

110 Anniversary: Nanoparticle mediated drug delivery for the treatment of Alzheimer's disease: Crossing the blood-brain barrier.

Alzheimer's disease is an irreversible neurodegenerative disorder affecting approximately 6 million Americans, 90% of which are over the age of 65. The hallmarks of the disease are represented by amyloid plaques and neurofibrillary tangles. While the neuronal characteristics of Alzheimer's disease are well known, current treatments only provide temporary relief of the disease symptoms.

Label-Free Detection of Tear Biomarkers Using Hydrogel-Coated Gold Nanoshells in a Localized Surface Plasmon Resonance-Based Biosensor.

The dependence of the localized surface plasmon resonance (LSPR) of noble-metal nanomaterials on refractive index makes LSPR a useful, label-free signal transduction strategy for biosensing. In particular, by decorating gold nanomaterials with molecular recognition agents, analytes of interest can be trapped near the surface, resulting in an increased refractive index surrounding the nanomaterial, and, consequently, a red shift in the LSPR wavelength. Ionic poly( N-isopropylacrylamide- co-methacrylic acid) (PNM) hydrogels were used as protein receptors because PNM nanogels exhibit a large increase in refractive index upon protein binding.

Vision for Functionally Decorated and Molecularly Imprinted Polymers in Regenerative Engineering.

The emerging field of regenerative engineering offers a great challenge and an even greater opportunity for materials scientists and engineers. How can we develop materials that are highly porous to permit cellular infiltration, yet possess sufficient mechanical integrity to mimic native tissues? How can we retain and deliver bioactive molecules to drive cell organization, proliferation, and differentiation in a predictable manner? In the following perspective, we highlight recent studies that have demonstrated the vital importance of each of these questions, as well as many others pertaining to scaffold development. We posit hybrid materials synthesized by molecular decoration and molecular imprinting as intelligent biomaterials for regenerative engineering applications.

Charged poly(N-isopropylacrylamide) nanogels for use as differential protein receptors in a turbidimetric sensor array.

Due to the high cost and environmental instability of antibodies, there is precedent for developing synthetic molecular recognition agents for use in diagnostic sensors. While these materials typically have lower specificity than antibodies, their cross-reactivity makes them excellent candidates for use in differential sensing routines. In the current work, we design a set of charge-containing poly(N-isopropylacrylamide) (PNIPAM) nanogels for use as differential protein receptors in a turbidimetric sensor array.

Molecularly Imprinted Intelligent Scaffolds for Tissue Engineering Applications.

The development of molecularly imprinted polymers (MIPs) using biocompatible production methods enables the possibility to further exploit this technology for biomedical applications. Tissue engineering (TE) approaches use the knowledge of the wound healing process to design scaffolds capable of modulating cell behavior and promote tissue regeneration. Biomacromolecules bear great interest for TE, together with the established recognition of the extracellular matrix, as an important source of signals to cells, both promoting cell-cell and cell-matrix interactions during the healing process.

Adult Human Mesenchymal Stem Cell Differentiation at the Cell Population and Single-Cell Levels Under Alternating Electric Current.

Mesenchymal stem cells, precursors that can differentiate into osteoblasts, chondrocytes, and adipocytes, have tremendous potential for derivation of cells with specific (e.g., osteogenic) phenotypes for tissue engineering and tissue regeneration applications.

Electrochemically Preadsorbed Collagen Promotes Adult Human Mesenchymal Stem Cell Adhesion.

The present article reports on the effect of electric potential on the adsorption of collagen type I (the most abundant component of the organic phase of bone) onto optically transparent carbon electrodes (OTCE) and its mediation on subsequent adhesion of adult, human, mesenchymal stem cells (hMSCs). For this purpose, adsorption of collagen type I was investigated as a function of the protein concentration (0.01, 0.