Low-Molecular-Weight PEGs for Cryopreservation of Stem Cell Spheroids.

Stem cell spheroids (SCSs) are a valuable tool in stem cell research and regenerative medicine. SCSs provide a platform for stem cell behavior in a more biologically relevant context with enhanced cell-cell communications. In this study, we investigated the recovery of SCSs after cryopreservation at -196 °C for 7 days.

Liquid Embolic Agents for Endovascular Embolization: A Review.

Endovascular embolization (EE) has been used for the treatment of blood vessel abnormalities, including aneurysms, AVMs, tumors, etc. The aim of this process is to occlude the affected vessel using biocompatible embolic agents. Two types of embolic agents, solid and liquid, are used for endovascular embolization.

In situ crosslinking temperature-responsive hydrogels with improved delivery, swelling, and elasticity for endovascular embolization.

Endovascular embolization of cerebral aneurysms is a common approach for reducing the risk of often-fatal hemorrhage. However, currently available materials used to occlude these aneurysms provide incomplete filling (coils) or require a complicated, time-consuming delivery procedure (solvent-exchange precipitating polymers). The objective of this work was to develop an easily deliverable in situ forming hydrogel that can occlude the entire volume of an aneurysm.

PNJ scaffolds promote microenvironmental regulation of glioblastoma stem-like cell enrichment and radioresistance.

Glioblastoma (GBM) brain tumors contain a subpopulation of self-renewing multipotent Glioblastoma stem-like cells (GSCs) that are believed to drive the near inevitable recurrence of GBM. We previously engineered temperature responsive scaffolds based on the polymer poly(-isopropylacrylamide--Jeffamine M-1000 acrylamide) (PNJ) for the purpose of enriching GSCs from patient-derived samples. Here, we used PNJ scaffolds to study microenvironmental regulation of self-renewal and radiation response in patient-derived GSCs representing classical and proneural subtypes.

What Is the Duration of Irrigation? An In Vitro Study of the Minimum Exposure Time to Eradicate Bacteria With Irrigation Solutions.

Background: Antiseptic irrigation solutions are commonly used by arthroplasty surgeons to reduce intraoperative bacterial colonization with the goal of reducing postoperative infections in the setting of primary total joint arthroplasty. Currently, the minimum irrigation time to eliminate common microbes implicated in periprosthetic joint infection is unknown. We sought to determine the minimum effective exposure time required to prevent growth of Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium acnes with common antiseptic solutions.

3D Printing-Enabled Nanoparticle Alignment: A Review of Mechanisms and Applications.

3D printing (additive manufacturing (AM)) has enormous potential for rapid tooling and mass production due to its design flexibility and significant reduction of the timeline from design to manufacturing. The current state-of-the-art in 3D printing focuses on material manufacturability and engineering applications. However, there still exists the bottleneck of low printing resolution and processing rates, especially when nanomaterials need tailorable orders at different scales.

In vivo evaluation of temperature-responsive antimicrobial-loaded PNIPAAm hydrogels for prevention of surgical site infection.

Surgical site infections (SSIs) are a persistent clinical challenge. Local antimicrobial delivery may reduce the risk of SSI by increasing drug concentrations and distribution in vulnerable surgical sites compared to what is achieved using systemic antimicrobial prophylaxis alone. In this work, we describe a comprehensive in vivo evaluation of the safety and efficacy of poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) [PNDJ], an injectable temperature-responsive hydrogel carrier for antimicrobial delivery in surgical sites.

Poly(N-isopropylacrylamide)-based dual-crosslinking biohybrid injectable hydrogels for vascularization.

Injectable hydrogels provide a powerful and non-invasive approach for numerous applications in cell transplantation, growth factor delivery, tissue regeneration and so forth. The properties of injectable hydrogels should be well-tuned for specific applications, where their overall design should ensure biocompatibility, non-toxicity, robust mechanical properties, and most importantly the ability to promote vascularization and integration with the host tissue/organ. Among these criteria, vascularization remains a key design element in the development of functional therapeutic hydrogels for successful translation into clinical settings.

Plasma-based fast-gelling biohybrid gels for biomedical applications.

Blood based biomaterials are widely researched and used in different biomedical applications including cell therapy, drug delivery, sealants etc. due to their biocompatibility and biodegradability. Blood derived gels are successfully used in clinical studies due to the presence of fibrinogen and several platelet growth factors.

Temperature-responsive PNDJ hydrogels provide high and sustained antimicrobial concentrations in surgical sites.

Local antimicrobial delivery is a promising strategy for improving treatment of deep surgical site infections (SSIs) by eradicating bacteria that remain in the wound or around its margins after surgical debridement. Eradication of biofilm bacteria can require sustained exposure to high antimicrobial concentrations (we estimate 100-1000 μg/mL sustained for 24 h) which are far in excess of what can be provided by systemic administration. We have previously reported the development of temperature-responsive hydrogels based on poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylate-co-Jeffamine M-1000 acrylamide) (PNDJ) that provide sustained antimicrobial release in vitro and are effective in treating a rabbit model of osteomyelitis when instilled after surgical debridement.

Therapeutic neovascularization promoted by injectable hydrogels.

The aim of therapeutic neovascularization is to repair ischemic tissues via formation of new blood vessels by delivery of angiogenic growth factors, stem cells or expansion of pre-existing cells. For efficient neovascularization, controlled release of growth factors is particularly necessary since bolus injection of molecules generally lead to a poor outcome due to inadequate retention within the injured site. In this regard, injectable hydrogels, made of natural, synthetic or hybrid biomaterials, have become a promising solution for efficient delivery of angiogenic factors or stem and progenitor cells for tissue repair, regeneration and neovascularization.

Oncolytic virus delivery: from nano-pharmacodynamics to enhanced oncolytic effect.

With the advancement of a growing number of oncolytic viruses (OVs) to clinical development, drug delivery is becoming an important barrier to overcome for optimal therapeutic benefits. Host immunity, tumor microenvironment and abnormal vascularity contribute to inefficient vector delivery. A number of novel approaches for enhanced OV delivery are under evaluation, including use of nanoparticles, immunomodulatory agents and complex viral-particle ligands along with manipulations of the tumor microenvironment.

Synthesis, characterization and application of biodegradable polymer grafted novel bioprosthetic tissue.

Animal tissue has an extended history of clinical use in applications like heart valve bioprosthesis devices, cardiovascular surgical applications etc. but often does not last long after implantation in the body due to rapid unwanted degradation. The goal of this work is to develop novel composite biomaterials by grafting biological tissue with synthetic, biodegradable polymers.

PNIPAAm-co-Jeffamine (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells.

Glioblastoma (GBM) is the most common adult primary brain tumor, and the 5-year survival rate is less than 5%. GBM malignancy is driven in part by a population of GBM stem-like cells (GSCs) that exhibit indefinite self-renewal capacity, multipotent differentiation, expression of neural stem cell markers, and resistance to conventional treatments. GSCs are enriched in specialized niche microenvironments that regulate stem phenotypes and support GSC radioresistance.

PNIPAAm-based biohybrid injectable hydrogel for cardiac tissue engineering.

Unlabelled: Injectable biomaterials offer a non-invasive approach to deliver cells into the myocardial infarct region to maintain a high level of cell retention and viability and initiate the regeneration process. However, previously developed injectable matrices often suffer from low bioactivity or poor mechanical properties. To address this need, we introduced a biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm-Gelatin-based injectable hydrogel with excellent bioactivity as well as mechanical robustness for cardiac tissue engineering.

Temperature responsive hydrogels enable transient three-dimensional tumor cultures via rapid cell recovery.

Recovery of live cells from three-dimensional (3D) culture would improve analysis of cell behaviors in tissue engineered microenvironments. In this work, we developed a temperature responsive hydrogel to enable transient 3D culture of human glioblastoma (GBM) cells. N-isopropylacrylamide was copolymerized with hydrophilic grafts and functionalized with the cell adhesion peptide RGD to yield the novel copolymer poly(N-isopropylacrylamide-co-Jeffamine(®) M-1000 acrylamide-co-hydroxyethylmethacrylate-RGD), or PNJ-RGD.

Bioengineered Scaffolds for 3D Analysis of Glioblastoma Proliferation and Invasion.

The invasion of malignant glioblastoma (GBM) cells into healthy brain is a primary cause of tumor recurrence and associated morbidity. Here, we describe a high-throughput method for quantitative measurement of GBM proliferation and invasion in three-dimensional (3D) culture. Optically clear hydrogels composed of thiolated hyaluronic acid and gelatin were chemically crosslinked with thiol-reactive poly(ethylene glycol) polymers to form an artificial 3D tumor microenvironment.

Local gentamicin delivery from resorbable viscous hydrogels is therapeutically effective.

Background: Local delivery can achieve the high antimicrobial concentrations necessary to kill biofilm-related microbes. Degradation times for resorbable carriers are too long. Hydrogels (gels of hydrophilic polymer in water) can degrade faster but release antimicrobials too quickly.

In vitro characteristics of a gelling PEGDA-QT polymer system with model drug release for cerebral aneurysm embolization.

A liquid-to-solid gelling polymer system, such as the poly(ethylene glycol) diacrylate-pentaerythritol tetrakis (3-mercaptopropionate) (PEGDA-QT) system, can fill cerebral aneurysms more completely than current embolization materials, reducing the likelihood of aneurysm recurrence. PEGDA-QT gels were formulated using PEGDA of different molecular weights (PEGDA575 and PEGDA700), and their characteristics were examined in vitro. Experiments examined gel time, mass change, crosslink integrity, cytotoxicity, and protein release capabilities.

In vitro and in vivo demonstration of physically and chemically in situ gelling NIPAAm-based copolymer system.

Poly(NIPAAm-co-hydroxyethylmethacarylate (HEMA)) acrylate and poly(NIPAAm-co-cysteine ethyl ester (CysOEt)) were synthesized and characterized by GPC(gel permeation chromatography), rheology, NMR (nuclear magnetic resonance), and Ellman's method. Upon mixing of these materials in aqueous solution, they formed gels immediately at body temperature owing to temperature-driven physical gelling, and gradually cured by chemical cross-linking through Michael-type addition reactions between thiols and acrylates. The rate of nucleophilic attack in the Michael-type addition reaction was shown to be highly dependent on the mole ratio of thiol to acrylate at neutral pH.

In vitro characteristics of a gelling PEGDA-QT polymer system with model drug release for cerebral aneurysm embolization.

A liquid-to-solid gelling polymer system, such as the poly(ethylene glycol) diacrylate-pentaerythritol tetrakis (3-mercaptopropionate) (PEGDA-QT) system, can fill cerebral aneurysms more completely than current embolization materials, reducing the likelihood of aneurysm recurrence. PEGDA-QT gels were formulated using PEGDA of different molecular weights (PEGDA and PEGDA ), and their characteristics were examined in vitro. Experiments examined gel time, mass change, crosslink integrity, cytotoxicity, and protein release capabilities.

In vivo embolization of lateral wall aneurysms in canines using the liquid-to-solid gelling PPODA-QT polymer system: 6-month pilot study.

Object: Over the past 20 years, endovascular embolization has become the preferred method of treating cerebral aneurysms. While there are many embolic devices on the market, none is ideal. In this study the authors investigated the use of a liquid-to-solid gelling polymer system-that is, poly(propylene glycol) diacrylate and pentaerythritol tetrakis (3-mercaptopropionate) (PPODA-QT)-to embolize in vivo aneurysms over a 6-month period.

Cytotoxicity, in vitro models and preliminary in vivo study of dual physical and chemical gels for endovascular embolization of cerebral aneurysms.

We report the evaluation of dual-gelling poly(N-isopropylacrylamide)-based polymer systems as embolic agents for intracranial aneurysms. These hydrogels undergo gelation physically via temperature-responsiveness of poly(NIPAAm) and chemically through a Michael-addition reaction between thiol and vinyl functional groups on the copolymers. Cytotoxicity studies were performed for biocompatibility of the hydrogels.

In situ forming, resorbable graft copolymer hydrogels providing controlled drug release.

In situ forming hydrogels are promising drug delivery vehicles due to their ease of delivery as liquids and their ability to be used in sites with irregular geometries. In this work, we report on in situ forming, resorbable hydrogels based on N-isopropylacrylamide (NIPAAm) as a fluid-like controlled release gel. These gels are the first resorbable NIPAAm-based gels providing controlled release without relying on affinity between the drug and device.

Comparison of properties between NIPAAm-based simultaneously physically and chemically gelling polymer systems for use in vivo.

In this work, a comparison between two different physical-chemical gels, poly(NIPAAm-co-cysteamine) with poly(NIPAAm-co-cysteamine-vinylsulfone) and poly(NIPAAm-co-cysteamine) with poly(NIPAAm-co-HEMA-acrylate), is made. These hydrogels undergo gelation via dual mechanisms: temperature sensitivity (physical gelation) and chemical crosslinking (chemical gelation). The advantages of using both gelation mechanisms are to reduce the creep experienced by purely physical gels and to increase the elastic modulus of purely chemical gels.