Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies.

The use of synthetic antigen-presenting cells to activate and expand engineered T cells for the treatment of cancers typically results in therapies that are suboptimal in effectiveness and durability. Here we describe a high-throughput microfluidic system for the fabrication of synthetic cells mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells. Compared with rigid or elastic microspheres, the synthetic viscoelastic T-cell-activating cells (SynVACs) led to substantial enhancements in the expansion of human CD8 T cells and to the suppression of the formation of regulatory T cells.

Harnessing Biomaterials to Amplify Immunity in Aged Mice through T Memory Stem Cells.

The durability of a protective immune response generated by a vaccine depends on its ability to induce long-term T cell immunity, which tends to decline in aging populations. The longest protection appears to arise from T memory stem cells (TMSCs) that confer high expandability and effector functions when challenged. Here we engineered artificial antigen presenting cells (aAPC) with optimized size, stiffness and activation signals to induce human and mouse CD8 TMSCs .

Precise Engineering of Growth Factor Presentation Using Extracellular Microenvironment-Mimicking Microfluidic Microparticles.

One of the main challenges in tissue engineering is finding a way to deliver specific growth factors (GFs) with precise spatiotemporal control over their presentation. Here, we report a novel strategy for generating microscale carriers with enhanced affinity for high content loading suitable for the sustained and localized delivery of GFs. Our developed microparticles can be injected locally and sustainably release encapsulated growth factors for up to 28 days.

An engineered biomaterial to harness the differentiation potential of endogenous human gingival mesenchymal stem cells (hGMSCs).

Here, we developed a stromal cell-derived factor-1a (SDF-1α) delivery biomaterial as an artificial polymeric-based niche with the ability to recruit local endogenous human gingival mesenchymal stem cells (hGMSCs) for craniofacial bone regeneration applications. Polydopamine-coated poly(ε-caprolactone) (PCL)-gelatin electrospun membranes were loaded with stromal cell-derived factor-1α (SDF-1α) via physical adsorption. Subsequently, the release profile of SDF-1α and the chemotactic capacity on human bone marrow mesenchymal stem cells (hBMMSCs) and hGMSCs were evaluated.

A mechanical niche promotes the rejuvenation of blood stem cells.

Zhang et al. show that the mechanical properties of a three-dimensional (3D) hydrogel can enhance the secretion of niche factors from bone marrow stromal cells, which in turn promotes the maintenance of hematopoietic stem cells (HSCs) and reverses aging hallmarks in HSCs.

Systemic enhancement of antitumour immunity by peritumourally implanted immunomodulatory macroporous scaffolds.

A tumour microenvironment abundant in regulatory T (T) cells aids solid tumours to evade clearance by effector T cells. Systemic strategies to suppress T cells or to augment immunity can elicit autoimmune side effects, cytokine storms and other toxicities. Here we report the design, fabrication and therapeutic performance of a biodegradable macroporous scaffold, implanted peritumourally, that releases a small-molecule inhibitor of transforming growth factor β to suppress T cells, chemokines to attract effector T cells and antibodies to stimulate them.

Cell-Taxi: Mesenchymal Cells Carry and Transport Clusters of Cancer Cells.

Cell clusters that collectively migrate from primary tumors appear to be far more potent in forming distant metastases than single cancer cells. A better understanding of the collective cell migration phenomenon and the involvement of various cell types during this process is needed. Here, an in vitro platform based on inverted-pyramidal microwells to follow and quantify the collective migration of hundreds of tumor cell clusters at once is developed.

Immunomodulatory Microneedle Patch for Periodontal Tissue Regeneration.

Periodontal diseases are caused by microbial infection and the recruitment of destructive immune cells. Current therapies mainly deal with bacteria elimination, but the regeneration of periodontal tissues remains a challenge. Here we developed a modular microneedle (MN) patch that delivered both antibiotic and cytokines into the local gingival tissue to achieve immunomodulation and tissue regeneration.

Engineered Delivery of Dental Stem-Cell-Derived Extracellular Vesicles for Periodontal Tissue Regeneration.

Periodontal disease begins as an inflammatory response to a bacterial biofilm deposited around the teeth, which over time leads to the destruction of tooth-supporting structures and consequently tooth loss. Conventional treatment strategies show limited efficacy in promoting regeneration of damaged periodontal tissues. Here, a delivery platform is developed for small extracellular vesicles (sEVs) derived from gingival mesenchymal stem cells (GMSCs) to treat periodontitis.

Biomaterial-based immunoengineering to fight COVID-19 and infectious diseases.

Infection by SARS-CoV-2 virus often induces the dysregulation of immune responses, tissue damage, and blood clotting. Engineered biomaterials from the nano- to the macroscale can provide targeted drug delivery, controlled drug release, local immunomodulation, enhanced immunity, and other desirable functions to coordinate appropriate immune responses and to repair tissues. Based on the understanding of COVID-19 disease progression and immune responses to SARS-CoV-2, we discuss possible immunotherapeutic strategies and highlight biomaterial approaches from the perspectives of preventive immunization, therapeutic immunomodulation, and tissue healing and regeneration.

Injectable Drug-Releasing Microporous Annealed Particle Scaffolds for Treating Myocardial Infarction.

Intramyocardial injection of hydrogels offers great potential for treating myocardial infarction (MI) in a minimally invasive manner. However, traditional bulk hydrogels generally lack microporous structures to support rapid tissue ingrowth and biochemical signals to prevent fibrotic remodeling toward heart failure. To address such challenges, a novel drug-releasing microporous annealed particle (drugMAP) system is developed by encapsulating hydrophobic drug-loaded nanoparticles into microgel building blocks via microfluidic manufacturing.

Augmenting T-cell responses to tumors by nanomanufacturing.

Recent innovations in immunoregulatory treatments have demonstrated both the impressive potential and vital role of T cells in fighting cancer. These treatments come at a cost, with systemic side effects including life-threatening autoimmunity and immune dysregulation the norm. Here, we developed an approach to locally synthesize immune therapies and in this way, avoid systemic toxicity.

Engineered Hydrogels for Brain Tumor Culture and Therapy.

Brain tumors' severity ranges from benign to highly aggressive and invasive. Bioengineering tools can assist in understanding the pathophysiology of these tumors from outside the body and facilitate development of suitable antitumoral treatments. Here, we first describe the physiology and cellular composition of brain tumors.

T-cell activation is modulated by the 3D mechanical microenvironment.

T cells recognize mechanical forces through a variety of cellular pathways, including mechanical triggering of both the T-cell receptor (TCR) and integrin LFA-1. Here we show that T cells can recognize forces arising from the mechanical rigidity of the microenvironment. We fabricated 3D scaffold matrices with mechanical stiffness tuned to the range 4-40 kPa and engineered them to be microporous, independently of stiffness.

An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats.

Cell-laden hydrogels are widely used in tissue engineering and regenerative medicine. However, many of these hydrogels are not optimized for use in the oral environment, where they are exposed to blood and saliva. To address these challenges, we engineered an alginate-based adhesive, photocrosslinkable, and osteoconductive hydrogel biomaterial (AdhHG) with tunable mechanical properties.

In situ bone tissue engineering using gene delivery nanocomplexes.

Gene delivery offers promising outcomes for functional recovery or regeneration of lost tissues at cellular and tissue levels. However, more efficient carriers are needed to safely and locally delivery of genetic materials. Herein, we demonstrate microfluidic-assisted synthesis of plasmid DNA (pDNA)-based nanocomplexe (NC) platforms for bone tissue regeneration.

Nano-in-Micro Dual Delivery Platform for Chronic Wound Healing Applications.

Here, we developed a combinatorial delivery platform for chronic wound healing applications. A microfluidic system was utilized to form a series of biopolymer-based microparticles with enhanced affinity to encapsulate and deliver vascular endothelial growth factor (VEGF). Presence of heparin into the structure can significantly increase the encapsulation efficiency up to 95% and lower the release rate of encapsulated VEGF.

Augmentation of T-Cell Activation by Oscillatory Forces and Engineered Antigen-Presenting Cells.

Activation of T cells by antigen presenting cells (APCs) initiates their proliferation, cytokine production, and killing of infected or cancerous cells. We and others have shown that T-cell receptors require mechanical forces for triggering, and these forces arise during the interaction of T cells with APCs. Efficient activation of T cells in vitro is necessary for clinical applications.

Enhancing cell seeding and osteogenesis of MSCs on 3D printed scaffolds through injectable BMP2 immobilized ECM-Mimetic gel.

Objective: Design of bioactive scaffolds with osteogenic capacity is a central challenge in cell-based patient-specific bone tissue engineering. Efficient and spatially uniform seeding of (stem) cells onto such constructs is vital to attain functional tissues. Herein we developed heparin functionalized collagen gels supported by 3D printed bioceramic scaffolds, as bone extracellular matrix (ECM)-mimetic matrices.

Hierarchically Patterned Polydopamine-Containing Membranes for Periodontal Tissue Engineering.

Periodontitis is a common chronic inflammatory disease that affects tooth-supporting tissues. We engineer a multifunctional periodontal membrane for the guided tissue regeneration of lost periodontal tissues. The major drawback of current periodontal membranes is the lack of tissue regeneration properties.

Mechanobiological Mimicry of Helper T Lymphocytes to Evaluate Cell-Biomaterials Crosstalk.

The unique properties of immune cells have inspired many efforts in engineering advanced biomaterials capable of mimicking their behaviors. However, an inclusive model capable of mimicking immune cells in different situations remains lacking. Such models can provide invaluable data for understanding immune-biomaterial crosstalk.

Polyserotonin Nanoparticles as Multifunctional Materials for Biomedical Applications.

Serotonin-based nanoparticles represent a class of previously unexplored multifunctional nanoplatforms with potential biomedical applications. Serotonin, under basic conditions, self-assembles into monodisperse nanoparticles via autoxidation of serotonin monomers. To demonstrate potential applications of polyserotonin nanoparticles for cancer therapeutics, we show that these particles are biocompatible, exhibit photothermal effects when exposed to near-infrared radiation, and load the chemotherapeutic drug doxorubicin, releasing it contextually and responsively in specific microenvironments.

Cytokine Secreting Microparticles Engineer the Fate and the Effector Functions of T-Cells.

T-cell immunotherapy is a promising approach for cancer, infection, and autoimmune diseases. However, significant challenges hamper its therapeutic potential, including insufficient activation, delivery, and clonal expansion of T-cells into the tumor environment. To facilitate T-cell activation and differentiation in vitro, core-shell microparticles are developed for sustained delivery of cytokines.

High aspect ratio phospho-calcified rock candy-like cellulose nanowhiskers of wastepaper applicable in osteogenic differentiation of hMSCs.

The aim of this study was to prepare cellulose nanowhiskers (CNWs) from wastepaper powder (WPP), as an environmentally friendly approach for obtaining the source material, which is a highly available and low-cost precursor for cellulose nanomaterial processing. Acid hydrolysis and calcification treatments were employed for extraction of CNWs and preparation of novel phospho-calcified cellulose nanowhiskers (PCCNWs). CNWs and PCCNWs were analyzed through optical microscopy (OM), scanning electron microscopy (SEM), Fourier-transformed infrared spectra (FTIR) and X-ray diffraction analysis (XRD).