M2e-Derived Peptidyl and Peptide Amphiphile Micelles as Novel Influenza Vaccines.

A significant problem with current influenza vaccines is their reliance on predictions of the most prevalent strains for the upcoming season, with inaccurate forecasts greatly reducing the overall efficacy of the immunization campaign. A universal influenza vaccine, which leverages epitopes conserved across many, if not all, strains of influenza, could reduce the need for extremely accurate forecasting. The highly conserved ectodomain of the influenza M2 protein contains a B cell epitope in the M2 region, making it a promising candidate as a universal influenza vaccine.

Adjuvant Delivery Method and Nanoparticle Charge Influence Peptide Amphiphile Micelle Vaccine Bioactivity.

Vaccines are an indispensable public health measure that have enabled the eradication, near elimination, and prevention of a variety of pathogens. As research continues and our understanding of immunization strategies develops, subunit vaccines have emerged as exciting alternatives to existing whole vaccine approaches. Unfortunately, subunit vaccines often possess weak antigenicity, requiring delivery devices and adjuvant supplementation to improve their utility.

Hydrogen Sulfide Delivery to Enhance Bone Tissue Engineering Cell Survival.

Though crucial for natural bone healing, local calcium ion (Ca) and phosphate ion (P) concentrations can exceed the cytotoxic limit leading to mitochondrial overload, oxidative stress, and cell death. For bone tissue engineering applications, HS can be employed as a cytoprotective molecule to enhance mesenchymal stem cell (MSC) tolerance to cytotoxic Ca/P concentrations. Varied concentrations of sodium hydrogen sulfide (NaSH), a fast-releasing HS donor, were applied to assess the influence of HS on MSC proliferation.

Vasoactive Intestinal Peptide Amphiphile Micelle Chemical Structure and Hydrophobic Domain Influence Immunomodulatory Potentiation.

Vasoactive intestinal peptide (VIP) is a neuropeptide capable of downregulating innate immune responses in antigen presenting cells (APCs) by suppressing their pro-inflammatory cytokine secretion and cell surface marker expression. Though VIP's bioactivity could possibly be leveraged as a treatment for transplant tolerance, drug delivery innovation is required to overcome its intrinsically limited cellular delivery capacity. One option is to employ peptide amphiphiles (PAs) which are lipidated peptides capable of self-assembling into micelles in water that can enhance cellular association.

4D Printing of shape-memory polymeric scaffolds for adaptive biomedical implantation.

4D printing has shown great potential in a variety of biomedical applications due to the adaptability and minimal invasiveness of fabricated devices. However, commonly employed shape memory polymers (SMPs) possess undesirable transition temperatures (Ts), leading to complications in implantation operations. Herein, we demonstrate 4D printing of a new SMP named poly(glycerol dodecanoate) acrylate (PGDA) with a T in a range of 20 °C - 37 °C making it appropriate for shape programming at room temperature and then shape deployment within the human body.

Effect of Dibasic Calcium Phosphate Incorporation on Cellulose Nanocrystal/Chitosan Hydrogel Properties for the Treatment of Vertebral Compression Fractures.

Vertebral compression fractures account for approximately 700,000 out of the 1.5 million total osteoporotic fractures that occur annually in the USA. There is growing interest in substituting currently utilized clinical treatments for vertebral compression fractures with an injectable, degradable, and bioactive system.

Inductive co-crosslinking of cellulose nanocrystal/chitosan hydrogels for the treatment of vertebral compression fractures.

Vertebral compression fractures are a very common consequence of osteoporosis for which injection of a non-biodegradable, non-bioactive, mechanically-stiff polymer bone cement into the vertebral body is the most common treatment. Recently, there has been growing interest in using bioactive, degradable, and bone biomechanics-matching products as an alternative approach for treating these fractures. In this research, we focused on creating injectable, chitosan-based hydrogels that can convey mechanical strength similar to vertebral bone as well as possess inherent osteoinductivity.

Aptamer-displaying peptide amphiphile micelles as a cell-targeted delivery vehicle of peptide cargoes.

Peptide amphiphile micelles (PAMs) are attractive vehicles for the delivery of a variety of therapeutic and prophylactic peptides. However, a key limitation of PAMs is their lack of preferential targeting ability. In this paper, we describe our design of a PAM system that incorporates a DNA oligonucleotide amphiphile (antitail amphiphile-AA) to form A/PAMs.

Peptide Amphiphile Micelle Vaccine Size and Charge Influence the Host Antibody Response.

Vaccines are one of the best health care advances ever developed, having led to the eradication of smallpox and near eradication of polio and diphtheria. While tremendously successful, traditional vaccines (i.e.

Instructive Design of Triblock Peptide Amphiphiles for Structurally Complex Micelle Fabrication.

Hydrophobically driven self-assembly is a well-understood principle that has been shown to facilitate micelle formation. Although quite useful, the library of structures accessible is limited to only a few simplistic geometric configurations that are suboptimal for complex applications. It is believed that other physical phenomena like hydrogen bonding and electrostatic interactions can be exploited to complement hydrophobic interactions allowing for the design of structurally complex, aggregated micelles.

Immunomodulatory vasoactive intestinal peptide amphiphile micelles.

Two different vasoactive intestinal peptide (VIP) amphiphiles have been formulated which readily form micelles of varying shapes. Interestingly, VIP micelle structure has been found to directly correlate to anti-inflammatory behavior providing evidence that these biomaterials can serve as a promising new therapeutic modality.

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.

Calcium and phosphate ions as simple signaling molecules with versatile osteoinductivity.

Due to the continually increasing clinical need to heal large bone defects, synthetic bone graft substitutes have become ever more necessary with calcium phosphates (CaP) widely used due to their similarity to the mineral component of bone. In this research, different concentrations of calcium ions (Ca), phosphate ions (P), or their combination were provided to mesenchymal stem cells (MSCs) to evaluate their influence on proliferation and differentiation. The results suggest that 1-16 mM Ca and 1-8 mM P is osteoinductive, but not cytotoxic.

Modular Peptide Amphiphile Micelles Improving an Antibody-Mediated Immune Response to Group A Streptococcus.

Inducing a strong and specific immune response is the hallmark of a successful vaccine. Nanoparticles have emerged as promising vaccine delivery devices to discover and elicit immune responses. Fine-tuning a nanoparticle vaccine to create an immune response with specific antibody and other cellular responses is influenced by many factors such as shape, size, and composition.

Controlled Ion Release from Novel Polyester/Ceramic Composites Enhances Osteoinductivity.

Due to the growing number of patients suffering from musculoskeletal defects and the limited supply of and sub-optimal outcomes associated with biological graft materials, novel biomaterials must be created that can function as graft substitutes. For bone regeneration, composite materials that mimic the organic and inorganic phases of natural bone can provide cues which expedite and enhance endogenous repair. Specifically, recent research has shown that calcium and phosphate ions are inherently osteoinductive, so controllably delivering their release holds significant promise for this field.

Porous polymeric platform repairs primates after spinal cord injury.

Amine-containing polymers immobilized on mesh and placed at trauma sites scavenge biomolecules that initiate a damaging immune response.

DAMPening the effects of trauma-induced inflammation.

Amine-containing polymers immobilized on mesh and placed at trauma sites scavenge biomolecules that initiate a damaging immune response.

Osteotropic nanoscale drug delivery systems based on small molecule bone-targeting moieties.

Bone-targeted drug delivery is an active research area because successful clinical applications of this technology can significantly advance the treatment of bone injuries and disorders. Molecules with bone-targeting potential have been actively investigated as promising moieties in targeted drug delivery systems. In general, bone-targeting molecules are characterized by their high affinity for bone and their predisposition to persist in bone tissue for prolonged periods, while maintaining low systemic concentrations.

Nanoparticles as synthetic vaccines.

As vaccines have transitioned from the use of whole pathogens to only the required antigenic epitopes, unwanted side effects have been decreased, but corresponding immune responses have been greatly diminished. To enhance immunogenicity, a variety of controlled release vehicles have been proposed as synthetic vaccines, but nanoparticles have emerged as particularly impressive systems due to many exciting publications. In specific, nanoparticles have been shown capable of not only desirable vaccine release, but can also be targeted to immune cells of interest, loaded with immunostimulatory substances termed adjuvants, or even induce desirable immune activating effects on their own.

Biocompatibility and characterization of a peptide amphiphile hydrogel for applications in peripheral nerve regeneration.

Peripheral nerve injury is a debilitating condition for which new bioengineering solutions are needed. Autografting, the gold standard in treatment, involves sacrifice of a healthy nerve and results in loss of sensation or function at the donor site. One alternative solution to autografting is to use a nerve guide conduit designed to physically guide the nerve as it regenerates across the injury gap.

Peptide amphiphile micelles self-adjuvant group A streptococcal vaccination.

Delivery system design and adjuvant development are crucially important areas of research for improving vaccines. Peptide amphiphile micelles are a class of biomaterials that have the unique potential to function as both vaccine delivery vehicles and self-adjuvants. In this study, peptide amphiphiles comprised of a group A streptococcus B cell antigen (J8) and a dialkyl hydrophobic moiety (diC16) were synthesized and organized into self-assembled micelles, driven by hydrophobic interactions among the alkyl tails.

Simple signaling molecules for inductive bone regenerative engineering.

With greater than 500,000 orthopaedic procedures performed in the United States each year requiring a bone graft, the development of novel graft materials is necessary. We report that some porous polymer/ceramic composite scaffolds possess intrinsic osteoinductivity as shown through their capacity to induce in vivo host osteoid mineralization and in vitro stem cell osteogenesis making them attractive synthetic bone graft substitutes. It was discovered that certain low crystallinity ceramics partially dissociate into simple signaling molecules (i.

Facile fabrication of polyanhydride/anesthetic nanoparticles with tunable release kinetics.

This work illustrates a two-step strategy for the fabrication of polymer/drug nanoparticles. Utilizing solvent/non-solvent precipitation and gaseous basification, composite nanoparticles with 0-100% drug loadings are fabricated. Drug release kinetics are dictated by nanoparticle composition allowing future tuning for therapeutic applications.

Nano-ceramic composite scaffolds for bioreactor-based bone engineering.

Background: Composites of biodegradable polymers and bioactive ceramics are candidates for tissue-engineered scaffolds that closely match the properties of bone. We previously developed a porous, three-dimensional poly (D,L-lactide-co-glycolide) (PLAGA)/nanohydroxyapatite (n-HA) scaffold as a potential bone tissue engineering matrix suitable for high-aspect ratio vessel (HARV) bioreactor applications. However, the physical and cellular properties of this scaffold are unknown.