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Hybrid hydrogel fibers were fabricated using hydrogel templates. On page 2146, D. Juncker, A. Khademhosseini, and co-workers show how these fibers containing different fluorescent microbeads have been assembled using textile processes, such as braiding and weaving, to create complex 3D patterns for bioengineering applications. The fabricated constructs with clinically relevant dimensions are mechanically stable.

Hydrogel templates are formed to entrap various pre-polymers prior to their crosslinking process. Upon the completion of the crosslinking process, an independent polymer network with the same fiber geometry is formed. The hydrogel template can be removed if necessary. As the proof-of-principle, fibers from various polymers are fabricated. The fabricated hybrid polymeric fibers are bioactive and can be bioprinted or assembled using textile processes. The approach can be used for creating complex 3D constructs for various applications.

Biodegradable nanofibrous polymeric substrates are used to fabricate suturable, elastic, and flexible electronics and sensors. The fibrous microstructure of the substrate makes it permeable to gas and liquid and facilitates the patterning process. As a proof-of-principle, temperature and strain sensors are fabricated on this elastic substrate and tested in vitro. The proposed system can be implemented in the field of bioresorbable electronics and the emerging area of smart wound dressings.

The fabrication of cell-laden structures with anisotropic mechanical properties while having a precise control over the distribution of different cell types within the constructs is important for many tissue engineering applications. Automated textile technologies for making fabrics allow simultaneous control over the color pattern and directional mechanical properties. The use of textile techniques in tissue engineering, however, demands the presence of cell-laden fibers that can withstand the mechanical stresses during the assembly process. Here, the concept of composite living fibers (CLFs) in which a core of load bearing synthetic polymer is coated by a hydrogel layer containing cells or microparticles is introduced. The core thread is drawn sequentially through reservoirs containing a cell-laden prepolymer and a crosslinking reagent. The thickness of the hydrogel layer increases linearly with to the drawing speed and the prepolymer viscosity. CLFs are fabricated and assembled using regular textile processes including weaving, knitting, braiding, winding, and embroidering, to form cell-laden structures. Cellular viability and metabolic activity are preserved during CLF fabrication and assembly, demonstrating the feasibility of using these processes for engineering functional 3D tissue constructs.

Commercial lipid emulsion of propofol (CLE) has several drawbacks including pain on injection and emulsion instability. In this paper, a novel nanocarrier system is introduced to improve stability and solubility of the poorly soluble anesthetic drug, propofol, for intravenous administration. In this paper, alginate is modified using a facile method in which the carboxylic group of alginate is grafted to octanol. The octanol–grafted alginate (Alg–C8) is then employed to prepare nanoparticles which are subsequently used for encapsulation of propofol. The nanoparticles are analyzed for their pH, osmolarity, particle size, stability, morphology and sleep recovery and the results are compared with CLE as control. It is revealed that nanoparticles have the average particle size of 180 nm ± 1.2 and spherical morphology which is less than CLE while their pH, osmolarity and profile of release of formulated nanoparticles are similar to those of CLE. In addition, the results show good chemical and physical storage stability for the nanoparticles at room temperature for at least 6 months compared to CLE as control. The animal sleep recovery test on rats shows no significant difference in time of unconsciousness and recovery of the righting reflex between nanoparticles and CLE. It is concluded that encapsulated nanoparticles introduced here could be a promising clinical intravenous system for delivery of poorly soluble anesthetic propofol. In addition, this study provides an efficient and facile method for preparing a carrier system for water insoluble drugs. [ABSTRACT FROM AUTHOR]

Epitope density has a profound impact on B cell responses to particulate Ags, the molecular mechanisms of which remain to be explored. To dissect the role of epitope density in this process, we have synthesized a series of liposomal particles, similar to the size of viruses, that display a model self-antigen peptide at defined surface densities. Immunization of C57BL/6J mice using these particles elicited both IgM and class-switched IgG1, IgG2b, and IgG3 autoreactive Abs that depended on the epitope density. In C57BL/6 gene knockout mice lacking either functional TCRs or MHC class II molecules on B cells, the liposomal particles also elicited IgM, IgG1, IgG2b, and IgG3 responses that were comparable in magnitudes to wild-type mice, suggesting that this B cell response was independent of cognate T cell help. Notably, the titer of the IgG in wild-type animals could be increased by more than 200-fold upon replacement of liposomes with bacteriophage Qb virus-like particles that displayed the same self-antigen peptide at comparable epitope densities. This enhancement was lost almost completely in gene knockout mice lacking either TCRs or MHC class II molecules on B cells. In conclusion, epitope density above a threshold on particulate Ags can serve as a stand-alone signal to trigger secretion of autoreactive and class-switched IgG in vivo in the absence of cognate T cell help or any adjuvants. The extraordinary immunogenicity of Qb viral-like particles relies, in large part, on their ability to effectively recruit T cell help after B cell activation. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo + self-assembly composed of azobenzene derivatives (Azo + ) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis -Azo + -mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo , including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo + molecules and loaded molecules. Conversely, visible light induces trans -Azo + formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Heparin is a negatively charged polysaccharide with various chain lengths and a hydrophilic backbone. Due to its fascinating chemical and physical properties, nontoxicity, biocompatibility, and biodegradability, heparin has been extensively used in different fields of medicine, such as cardiovascular and hematology. This review highlights recent and future advancements in designing materials based on heparin for various biomedical applications. The physicochemical and mechanical properties, biocompatibility, toxicity, and biodegradability of heparin are discussed. In addition, the applications of heparin-based materials in various biomedical fields, such as drug/gene delivery, tissue engineering, cancer therapy, and biosensors, are reviewed. Finally, challenges, opportunities, and future perspectives in preparing heparin-based materials are summarized., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Bone defects, with second highest demand for surgeries around the globe, may lead to serious health issues and negatively influence patient lives. The advances in biomedical engineering and sciences have led to the development of several creative solutions for bone defect treatment. This review provides a brief summary of bone graft materials, an organized overview of top-down and bottom-up (bio)manufacturing approaches, plus a critical comparison between advantages and limitations of each method. We specifically discuss additive manufacturing techniques and their operation mechanisms in detail. Next, we review the hybrid methods and promising future directions for bone grafting, while giving a comprehensive US-FDA regulatory science perspective, biocompatibility concepts and assessments, and clinical considerations to translate a technology from a research laboratory to the market. The topics covered in this review could potentially fuel future research efforts in bone tissue engineering, and perhaps could also provide novel insights for other tissue engineering applications.

Potent anti-tumor T cell response and efficient intratumoral T cell infiltration are the major challenges for therapeutic cancer vaccines. To address these issues, a nano-vaccine system has been designed to promote anti-tumor T cell responses, and intratumoral infiltration was examined in various murine tumor models. Subcutaneous vaccination with nanodiscs carrying human papillomavirus (HPV)-16 E7 antigen elicits as high as ~32% E7-specific CD8 α + T cell responses in circulation, representing a 29-fold improvement over the soluble peptide vaccination. Importantly, nanodisc vaccination also promotes robust intratumoral T cell infiltration and eliminates HPV16 E6/E7-expressing TC-1 tumors at mucosal sites, including lungs, inner lip, and intravaginal tissues. In a benchmark study with a live Listeria vaccine combined with anti-PD-1 IgG, nanodiscs plus anti-PD-1 immune checkpoint blockade elicits comparable levels of T cell responses with anti-tumor efficacy. Furthermore, compared with Complete Freund's Adjuvant combined with tetanus toxoid, nanodisc vaccination in HLA-A02 mice generates >200-fold stronger IFN-γ+ T cell responses against a neoantigen from an HLA-A02 melanoma patient. Overall, these results show that the nanodisc system is a promising cancer vaccine platform for inducing anti-tumor T cell responses., Competing Interests: A patent application for nanodisc vaccines has been filed, with J.J.M., A.S., and R.K. as inventors. J.J.M. and A.S. are co-founders of EVOQ Therapeutics, LLC. that develops the nanodisc technology for vaccine applications. P.B.S. and R.J. are employees of Bristol Myers Squibb. C.J.W. is a co-founder, equity holder, and SAB member of Neon Therapeutics, Inc. D.B.K. has previously advised Neon Therapeutics, and has received consulting fees from Gerson Lehrman Group, Guidepoint, Neon Therapeutics, System analytic Ltd and The Science Advisory Board. D.B.K. owns equity in Aduro Biotech, Agenus Inc., Armata Pharmaceuticals, Biomarin Pharmaceutical Inc., Breakbio Corp., Bristol Myers Squibb Co., Celldex Therapeutics Inc., Editas Medicine Inc., Exelixis Inc., Gilead Sciences Inc., IMV Inc., Lexicon Pharmaceuticals Inc., and Stemline Therapeutics Inc.