Protoacoustic range verification by direct comparison with beam range measurements using a tissue-equivalent polymer gel.

Background And Purpose: Protoacoustics offers a promising method for in vivo range verification in proton therapy. To experimentally assess the protoacoustic range accuracy, conventional tissue-mimicking phantoms (TMPs) often require Monte Carlo (MC) simulations to estimate the ground truth. However, limited knowledge of material properties and/or insufficient fine-tuning of dose models can introduce range errors in MC simulations.

Tendon Tissue Regeneration With Cell Orientation Using an Injectable Alginate-Cell Cross-linked Gel.

Background: Tendons have a limited blood supply and form inferior scar tissue during repair, which increases the risk of reruptures, causes complications, and limits regenerative capacity. Current methods to repair injured tendon tissue use solid scaffolds, which carry the risk of contamination (infections) and require open surgery for transplantation.

Hypothesis: Alginate-cell cross-linked gels, which can be applied by a percutaneous injection and transmit mechanical stress to cells via direct cell interaction, could induce tendon tissue regeneration.

Establishment of a novel method for differentiating into dopaminergic neurons using charged hydrogels.

Parkinson's disease (PD) is a neurodegenerative disease primarily affecting the central nervous system and impacting both the motor system and non-motor systems. Although administration of L-DOPA is effective, it is not a fundamental treatment and has side effects such as diurnal fluctuation and dyskinesia, highlighting the need for new treatment methods. There is a growing interest in dopaminergic neuron transplantation as a potential treatment.

Soft hydrogel-embedded ceramic skeleton mimicking bone structure sacrificial bond concept.

Bone, consisting of calcium phosphate minerals, rigid collagen fibrils, and acidic proteins, exhibits stiff and tough mechanical properties. On a molecular scale, covalent cross-linking in proteins and ionic interactions within proteins and at the protein-mineral boundary contribute to bone's toughness. In addition, hierarchical structures, like the sponge-like arrangement, are also crucial for the energy dissipation system in bone.

Real-Space Visualization of Charged Polymer Network of Hydrogel by Double Network Strategy and Mineral Staining.

Hydrogels consist of three-dimensional (3D) and complicated polymer networks that determine their physical properties. Among the methods for structural analyses of hydrogels, the real-space imaging of a polymer network of hydrogels on a nanometer scale is one of the optimal methods; however, it is highly challenging. In this study, we propose a direct observation method for cationic polymer networks using transmission electron microscopy (TEM).

Fractographic mirror law for brittle fracture of nonlinear elastic soft materials.

Mirror radius analysis of fractured surfaces is a powerful fractographic method for determining the cause of failure in linear elastic hard materials because it does not require prior loading information. However, mirror analysis for soft materials is lacking. In this study, we established a general mirror radius law for nonlinear elastic soft materials using highly deformable brittle hydrogels.

Engineering of an electrically charged hydrogel implanted into a traumatic brain injury model for stepwise neuronal tissue reconstruction.

Neural regeneration is extremely difficult to achieve. In traumatic brain injuries, the loss of brain parenchyma volume hinders neural regeneration. In this study, neuronal tissue engineering was performed by using electrically charged hydrogels composed of cationic and anionic monomers in a 1:1 ratio (C1A1 hydrogel), which served as an effective scaffold for the attachment of neural stem cells (NSCs).

ERK MAP Kinase Signaling Regulates RAR Signaling to Confer Retinoid Resistance on Breast Cancer Cells.

Retinoic acid (RA) and its synthetic derivatives, retinoids, have been established as promising anticancer agents based on their ability to regulate cell proliferation and survival. Clinical trials, however, have revealed that cancer cells often acquire resistance to retinoid therapy. Therefore, elucidation of underlying mechanisms of retinoid resistance has been considered key to developing more effective use of retinoids in cancer treatment.

Nanoscale TEM Imaging of Hydrogel Network Architecture.

In this work, the authors succeed in direct visualization of the network structure of synthetic hydrogels with transmission electron microscopy (TEM) by developing a novel staining and network fixation method. Such a direct visualization is not carried out because sample preparation and obtaining sufficient contrast are challenging for these soft materials. TEM images reveal robust heterogeneous network architectures at mesh size scale and defects at micro-scale.

Force-triggered rapid microstructure growth on hydrogel surface for on-demand functions.

Living organisms share the ability to grow various microstructures on their surface to achieve functions. Here we present a force stamp method to grow microstructures on the surface of hydrogels based on a force-triggered polymerisation mechanism of double-network hydrogels. This method allows fast spatial modulation of the morphology and chemistry of the hydrogel surface within seconds for on-demand functions.

The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance.

How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H , a mouse gain-of-function variant, and found that they had higher jumping abilities and faster running speeds than wild-type or muscle-specific knock-in mice.

Hydroxyapatite-hybridized double-network hydrogel surface enhances differentiation of bone marrow-derived mesenchymal stem cells to osteogenic cells.

Recently, we have developed a hydroxyapatite (HAp)-hybridized double-network (DN) hydrogel (HAp/DN gel), which can robustly bond to the bone tissue in the living body. The purpose of this study is to clarify whether the HAp/DN gel surface can differentiate the bone marrow-derived mesenchymal stem cells (MSCs) to osteogenic cells. We used the MSCs which were harvested from the rabbit bone marrow and cultured on the polystyrene (PS) dish using the autogenous serum-supplemented medium.

Ultrapurified Alginate Gel Containing Bone Marrow Aspirate Concentrate Enhances Cartilage and Bone Regeneration on Osteochondral Defects in a Rabbit Model.

Background: Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects.

Hypothesis: The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects.

Study Design: Controlled laboratory study.

Tough Double Network Hydrogel and Its Biomedical Applications.

Soft and wet hydrogels have many similarities to biological tissues, though their mechanical fragility had been one of the biggest obstacles in biomedical applications. Studies and developments in double network (DN) hydrogels have elucidated how to create tough gels universally based on sacrificial bond principles and opened a path for biomedical application of hydrogels in regenerative medicine and artificial soft connective tissues, such as cartilage, tendon, and ligament, which endure high tension and compression. This review explores a universal toughening mechanism for and biomedical studies of DN hydrogels.

Bone Marrow Aspirate Concentrate Combined with in Situ Forming Bioresorbable Gel Enhances Intervertebral Disc Regeneration in Rabbits.

Background: The current surgical procedure of choice for intervertebral disc (IVD) herniation is discectomy, which induces postoperative IVD degeneration. Thus, cell-based therapies, as a 1-step simple procedure, are desired because of the poor capacity of IVDs for self-repair. The aim of this study was to investigate the repair efficacy of ultra-purified alginate (UPAL) gels containing bone marrow aspirate concentrate (BMAC) for the treatment of discectomy-associated IVD degeneration in rabbits.

Isotope Microscopic Observation of Osteogenesis Process Forming Robust Bonding of Double Network Hydrogel to Bone.

Tough double network (DN) hydrogels are promising substitutes of soft supporting tissues such as cartilage and ligaments. For such applications, it is indispensable to robustly fix the hydrogels to bones with medically feasible methods. Recently, robustly bonding the DN hydrogels to defected bones of rabbits in vivo has been proved successful.

Chitin-Based Double-Network Hydrogel as Potential Superficial Soft-Tissue-Repairing Materials.

Chitin is a biopolymer, which has been proven to be a biomedical material candidate, yet the weak mechanical properties seriously limit their potentials. In this work, a chitin-based double-network (DN) hydrogel has been designed as a potential superficial repairing material. The hydrogel was synthesized through a double-network (DN) strategy composing hybrid regenerated chitin nanofiber (RCN)-poly (ethylene glycol diglycidyl ether) (PEGDE) as the first network and polyacrylamide (PAAm) as the second network.

Hydrogels toughened by biominerals providing energy-dissipative sacrificial bonds.

Inspired by bone tissues, we mineralized low crystalline hydroxyapatite (HAp) particles in double network (DN) hydrogels, and we observed that the HAp minerals toughen the gels. The contribution of dissipated energy from HAp minerals was over 500% higher than that from the polymer during tensile deformation. We elucidated that the amorphous parts in the HAp minerals break at deformation, acting as energy-dissipative sacrificial bonds.

Surface charge dominated protein absorption on hydrogels.

Soft tissue engineering requires antifouling materials that are biocompatible and mechanically flexible. Conventional hydrogels containing more than 70 wt% water are thus promising antifouling material candidates. However, some hydrogels are difficult to apply in internal body organs because of undesirable protein absorption on their surfaces.

Instant Thermal Switching from Soft Hydrogel to Rigid Plastics Inspired by Thermophile Proteins.

Proteins of thermophiles are thermally stable in a high-temperature environment, adopting a strategy of enhancing the electrostatic interaction in hydrophobic media at high temperature. Herein, inspired by the molecular mechanism of thermally stable proteins, the synthesis of novel polymer materials that undergo ultrarapid, isochoric, and reversible switching from soft hydrogels to rigid plastics at elevated temperature is reported. The materials are developed from versatile, inexpensive, and nontoxic poly(acrylic acid) hydrogels containing calcium acetate.

Osteochondral Autograft Transplantation Technique Augmented by an Ultrapurified Alginate Gel Enhances Osteochondral Repair in a Rabbit Model.

Background: One of the most important limitations of osteochondral autograft transplantation (OAT) is the adverse effect on donor sites in the knee. To decrease the number and/or size of osteochondral defects, we devised a method with biomaterial implantation after OAT.

Hypothesis: OAT augmented by ultrapurified alginate (UPAL) gel enhances cartilage repair capacity.