Three-dimensional (3D) cancer cell culture models such as tumor spheroids better recapitulate tumors than conventional two-dimensional (2D) models. However, two major challenges limit the routine use of 3D tumor spheroids. Firstly, most existing methods of generating tumor spheroids are not high-throughput.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2024
Hemostatic devices are critical for managing emergent severe bleeding. With the increased use of anticoagulant therapy, there is a need for next-generation hemostats. We rationalized that a hemostat with an architecture designed to increase contact with blood, and engineered from a material that activates a distinct and undrugged coagulation pathway can address the emerging need.
View Article and Find Full Text PDFDespite advances in bone tissue engineering, fabricating a scaffold which can be used as an implant for large bone defects remains challenge. One of the great importance in fabricating a biomimetic bone implant is considering the possibility of the integration of the structure and function of implants with hierarchical structure of bone. Herein, we propose a method to mimic the structural unit of compact bone, osteon, with spatial pattern of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) in the adjacent layers that mimic Haversian canal and lamella, respectively.
View Article and Find Full Text PDFNew antibiotics should ideally exhibit activity against drug-resistant bacteria, delay the development of bacterial resistance to them and be suitable for local delivery at desired sites of infection. Here, we report the rational design, via molecular-docking simulations, of a library of 17 candidate antibiotics against bone infection by wild-type and mutated bacterial targets. We screened this library for activity against multidrug-resistant clinical isolates and identified an antibiotic that exhibits potent activity against resistant strains and the formation of biofilms, decreases the chances of bacterial resistance and is compatible with local delivery via a bone-cement matrix.
View Article and Find Full Text PDFCancer progresses by evading the immune system. Elucidating diverse immune evasion strategies is a critical step in the search for next-generation immunotherapies for cancer. Here we report that cancer cells can hijack the mitochondria from immune cells via physical nanotubes.
View Article and Find Full Text PDFTargeted delivery of drugs to tumor cells, which circumvent resistance mechanisms and induce cell killing, is a lingering challenge that requires innovative solutions. Here, we provide two bioengineered strategies in which nanotechnology is blended with cancer medicine to preferentially target distinct mechanisms of drug resistance. In the first 'case study', we demonstrate the use of lipid-drug conjugates that target molecular signaling pathways, which result from taxane-induced drug tolerance via cell surface lipid raft accumulations.
View Article and Find Full Text PDFThe interaction of tumor cells with blood vessels is one of the key steps during cancer metastasis. Metastatic cancer cells exhibit phenotypic state changes during this interaction: (1) they form tunneling nanotubes (TNTs) with endothelial cells, which act as a conduit for intercellular communication; and (2) metastatic cancer cells change in order to acquire an elongated phenotype, instead of the classical cellular aggregates or mammosphere-like structures, which it forms in three-dimensional cultures. Here, we demonstrate mechanistically that a siRNA-based knockdown of the exocyst complex protein Sec3 inhibits TNT formation.
View Article and Find Full Text PDFAdvanced microfabrication technologies and biocompatible hydrogel materials facilitate the modeling of 3D tissue microenvironment. Encapsulation of cells in hydrogel microparticles offers an excellent high-throughput platform for investigating multicellular interaction with their surrounding microenvironment. Compartmentalized microparticles support formation of various unique cellular structures.
View Article and Find Full Text PDFBlood vessels and nerve fibers are distributed throughout the entirety of skeletal tissue, and play important roles during bone development and fracture healing by supplying oxygen, nutrients, and cells. However, despite the successful development of bone mimetic materials that can replace damaged bone from a structural point of view, most of the available bone biomaterials often do not induce sufficient formation of blood vessels and nerves. In part, this is due to the difficulty of integrating and regulating multiple tissue types within artificial materials, which causes a gap between native skeletal tissue.
View Article and Find Full Text PDFBone nonunion may occur when the fracture is unstable, or blood supply is impeded. To provide an effective treatment for the healing of nonunion defects, we introduce an injectable osteogenic hydrogel that can deliver cells and vasculogenic growth factors. We used a silicate-based shear-thinning hydrogel (STH) to engineer an injectable scaffold and incorporated polycaprolactone (PCL) nanoparticles that entrap and release vasculogenic growth factors in a controlled manner.
View Article and Find Full Text PDFUnlabelled: The inorganic part of human bone is mainly composed of hydroxyapatite (HAP: Ca(PO)(OH)) and whitlockite (WH: CaMg(HPO)(PO)) minerals, where the WH phase occupies up to 20-35% of total weight. These two bone minerals have different crystal structures and physicochemical properties, implying their distinguished role in bone physiology. However, until now, the biological significance of the presence of a certain ratio between HAP and WH in bone is unclear.
View Article and Find Full Text PDFSutures are one of the most widely used devices for adhering separated tissues after injury or surgery. However, most sutures require knotting, which can create a risk of inflammation, and can act as mechanically weak points that often result in breakage and slipping. Here, an anchoring suture is presented with a design that facilitates its propagation parallel to the suturing direction, while maximizing its resistive force against the opposite direction of external force to lock its position in tissues.
View Article and Find Full Text PDFChondroitin sulfate (CS) is the major component of glycosaminoglycan in connective tissue. In this study, we fabricated methacrylated PEGDA/CS-based hydrogels with varying CS concentration (0, 1, 5, and 10%) and investigated them as biomineralizing three-dimensional scaffolds for charged ion binding and depositions. Due to its negative charge from the sulfate group, CS exhibited an osteogenically favorable microenvironment by binding charged ions such as calcium and phosphate.
View Article and Find Full Text PDFBone is one of the major organs of the human body; it supports and protects other organs, produces blood cells, stores minerals, and regulates hormones. Therefore, disorders in bone can cause serious morbidity, complications, or mortality of patients. However, despite the significant occurrence of bone diseases, such as osteoarthritis (OA), osteoporosis (OP), non-union bone defects, bone cancer, and myeloma-related bone disease, their effective treatments remain a challenge.
View Article and Find Full Text PDFThe aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano- and micro-technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell-matrix interactions at the nanoscale.
View Article and Find Full Text PDFNanotechnology offers significant potential in regenerative medicine, specifically with the ability to mimic tissue architecture at the nanoscale. In this perspective, we highlight key achievements in the nanotechnology field for successfully mimicking the composition and structure of different tissues, and the development of bio-inspired nanotechnologies and functional nanomaterials to improve tissue regeneration. Numerous nanomaterials fabricated by electrospinning, nanolithography and self-assembly have been successfully applied to regenerate bone, cartilage, muscle, blood vessel, heart and bladder tissue.
View Article and Find Full Text PDFThe development of a multimaterial extrusion bioprinting platform is reported. This platform is capable of depositing multiple coded bioinks in a continuous manner with fast and smooth switching among different reservoirs for rapid fabrication of complex constructs, through digitally controlled extrusion of bioinks from a single printhead consisting of bundled capillaries synergized with programmed movement of the motorized stage.
View Article and Find Full Text PDFBone remodeling process relies on complex signaling pathway between osteoblasts and osteoclasts and control mechanisms to achieve homeostasis of their growth and differentiation. Despite previous achievements in understanding complicated signaling pathways between cells and bone extracellular matrices during bone remodeling process, a role of local ionic concentration remains to be elucidated. Here, we demonstrate that synthetic whitlockite (WH: CaMg(HPO)(PO)) nanoparticles can recapitulate early-stage of bone regeneration through stimulating osteogenic differentiation, prohibiting osteoclastic activity, and transforming into mechanically enhanced hydroxyapatite (HAP)-neo bone tissues by continuous supply of PO and Mg under physiological conditions.
View Article and Find Full Text PDFGraphene and its chemical derivatives have been a pivotal new class of nanomaterials and a model system for quantum behavior. The material's excellent electrical conductivity, biocompatibility, surface area and thermal properties are of much interest to the scientific community. Two-dimensional graphene materials have been widely used in various biomedical research areas such as bioelectronics, imaging, drug delivery, and tissue engineering.
View Article and Find Full Text PDFPEEK is a bioinert material that does not chemically bind to native bone tissue and thus formation of natural bone-like hydroxyapatite (HA) coating layer on PEEK has been an important challenge to improve biocompatibility and to preserve mechanical property of PEEK. Among various coating techniques, cold-spray coating method is suitable to form stable HA coating layer on PEEK while maintaining their chemical properties, because it can be conducted in relatively low-temperature range. Therefore, in this research, we used cold-spray coating method to form a thick layer of HA on the topographically complex PEEK substrates with periodic ridges on the surface and implanted in iliac bone defects of minipigs which is known to be similar with human body system.
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