Biocompatible single-chain polymer nanoparticles loaded with an antigen mimetic as potential anticancer vaccine.

The "pancarcinoma" Tn antigen (αGalNAc-O-Ser/Thr) is a tumor-associated carbohydrate antigen (TACA) overexpressed on the surface of cancer cells and suitable target for anticancer vaccines. However, TACAs commonly show weak immunogenicity, low in vivo stability, and poor bioavailability. To address these issues, the development of physiologically stable TACA synthetic mimetics and novel nanocarriers for multivalent display are object of intense research. Nanomaterials represent suitable scaffolds to multimerize antigens, but absence of toxicity, easy functionalization and capability to incorporate biomolecules are compulsory characteristics for vaccine nanocarriers. Here, we report on the conjugation of a synthetic Tn-antigen mimetic to biocompatible and water-dispersible dextran-based single-chain nanoparticles (DXT-SCPNs). In vitro stimulation of PBMCs and analysis of interleukins production indicated a specific innate immune modulation mediated by the multivalent presentation of the Tn mimetic at the nanoparticle surface. These preliminary results pave the way for the development of Tn-mimetic clusters on biocompatible DXT-SCPN for TACA-based vaccines.

Self-Healing Dynamic Hydrogel as Injectable Shock-Absorbing Artificial Nucleus Pulposus.

The intervertebral discs (IVDs) provide unique flexibility to the spine and exceptional shock absorbing properties under impact. The inner core of the IVD, the nucleus pulposus (NP) is responsible for this adaptive behavior. Herein, we evaluate an injectable, self-healing dynamic hydrogel (DH) based on gold(I)-thiolate/disulfide (Au-S/SS) exchange as NP replacement in a spine motion segment model. For the first time, we report the application of dynamic covalent hydrogels inside biological tissues. The dynamic exchange between Au-S species and disulfide bonds (SS) resulted in self-healing ability and frequency-dependent stiffness of the hydrogel, which was also confirmed in spine motion segments. Injection of preformed DH into nucleotomized IVDs restored the full biomechanical properties of intact IVDs, including the stiffening effect observed at increasing frequencies, which cannot be achieved with conventional covalent hydrogel. DH has the potential to counteract IVD degeneration associated with high frequency vibrations. Self-healing properties, confirmed by rheology studies and macroscopic observation after injection, were required to inject preformed DH, which recovered its mechanical integrity and microstructure to act as an artificial NP. On the other hand, covalent hydrogel did not show any restoration of NP properties as this conventional material suffered irreversible damages after injection, which demonstrates that the dynamic properties are crucial for this application. The persistence of DH in the IVD space following cyclic high-frequency loading, confirmed by tomography after mechanical testing, suggests that this material would have long life span as an injectable NP replacement material.

Injectable and Self-Healing Dynamic Hydrogels Based on Metal(I)-Thiolate/Disulfide Exchange as Biomaterials with Tunable Mechanical Properties.

Despite numerous strategies involving dynamic covalent bonds to produce self-healing hydrogels with similar frequency-dependent stiffness to native tissues, it remains challenging to use biologically relevant thiol/disulfide exchange to confer such properties to polymeric networks. Herein, we report a new method based on Metal(I) [Au(I) or Ag(I)] capping to protect thiolates from aerial oxidation without preventing thiolate/disulfide exchange. Dynamic hydrogels were readily prepared by injecting simultaneously aqueous solutions of commercially available HAuCl4 and 4-arm thiol-terminated polyethylene glycol [(PEGSH)4], resulting in a network containing a mixture of Au(I)-thiolate (Au-S) and disulfide bonds (SS). While the dynamic properties of the hydrogel were closely dependent on the pH, the mechanical properties could be easily tuned by adjusting (PEGSH)4 concentration and amount of Au-S, as judged by dynamic rheology studies. Permanent Au-S/SS exchange at physiological pH conferred self-healing behavior and frequency-dependent stiffness to the hydrogel. In addition, in vitro studies confirmed that Au-based dynamic material was not cytotoxic to human dermal fibroblasts, demonstrating its potential use as a medical device. Dynamic hydrogels obtained using Ag(I) ions demonstrated that the exchange reaction was not affected by the nature of the Metal(I) capping. Finally, this efficient thiolate capping strategy offers a simple way to produce injectable and self-healing dynamic hydrogels from virtually any thiol-containing polymers.

Neural-competent cells of adult human dermis belong to the Schwann lineage.

Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR(+) precursors of human foreskin can be ascribed to the Schwann (CD56(+)) and perivascular (CD56(-)) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR(+)CD56(+) Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.

Aurophilically cross-linked "dynamic" hydrogels mimicking healthy synovial fluid properties.

We report a new supramolecular dynamic hydrogel, based on a new concept of reversible aurophilic cross-linkers, mimicking the rheological behaviour of healthy synovial fluid under physiological conditions with good cell viability.