Engineered regeneration最新文献

Cells, wrapped among their neighbors and surrounding extracellular matrix (ECM), form cell-cell adhesions and cell-ECM adhesions. Extracellular biophysical cues exert a far-reaching influence on a sweeping of cell behaviors, including signal transduction, gene expression, and fate determination. Cell-cell adhesions mediated by intercellular adhesion molecules bridge the membranes of adjacent cells through either heterophilic or homophilic adhesive interactions, playing a critical part in multicellular structural maintenance and, therefore, a foundation for multicellular organisms. Cell-ECM adhesions are derived from the interaction between cell adhesion receptors and multi-adhesive matrix proteins to ensure cell and tissue cohesion. Whereas cells not only unilaterally respond to certain cues from extracellular environment but can also alter the physicochemical profiles of the externalities and hence hold important implications for clinical applications. The essential function of cell adhesions has created tremendous interests in developing methods for measuring and studying cell adhesion properties, namely, cellular force. Here, we describe the collection of cell adhesive inputs on cellular signaling cascades and the “crosstalk” between cell-cell adhesions and cell-ECM adhesions. Furthermore, we provide the summary of the current methods to measure such cell adhesive forces.

Sensory hair cells are responsible for detecting and transmitting sound in the inner ear, and damage to HCs leads to hearing loss. HCs do not regenerate spontaneously in adult mammals, which makes the hearing loss permanent. However, hair cells and supporting cells have the same precursors in the inner ear, and in newborn mice, the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells. Here, we demonstrate the role of the Ras association domain family member 2 (Rassf2) in supporting cell to hair cell trans-differentiation in the inner ear. Using the AAV vector (AAV-ie) to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids. Also, AAV-Rassf2 enhanced the regenerative ability of Lgr5⁺ SCs in the postnatal cochlea without impairing hearing, and this might due to the modulation of the Wnt, Hedgehog and Notch signaling pathways. Furthermore, AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model. In summary, our results suggest that Rassf2 is a key component in HC regenerative repair, and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair.

Multiplex, rapid and accurate virus quantification plays a great value in biomedical detection. Here, a novel one step, wash-free immunoassay platform based bioinspired PhC barcodes for multiplexed virus quantification was explored. PhC barcodes were decorated with PDA by self-polymerization of DA, thus this nanocomposite hybridized PhC barcodes facilitated the adsorption of FITC labelled antibodies and quenched itself photoluminescent, allowing a fast responsive composite platform. In the presence of target analyte, the FITC-labelled detection antibody was released from the surface of PDA decorated microcarrier to specifically bind to the target analyte, thus recovered the photoluminescence. In addition, the PhC microcarrier was enabled to carry out various color barcode for different targets detection though tuning internal periodic structures. Based on these excellent performances of the nanocomposite barcode, this method can not only capture H1N1, H5N1, SARS-CoV-2 simultaneously with rapid, accuracy but also accomplish multiplex quantification detection with high-sensitivity. Furthermore, our developed platform was also achieved with high-sensitivity and high-specificity through the verification of clinical samples, thus laying out a new avenue for multiplex virus detection in clinical diagnosis.

As a new kind of microcarrier device, microneedles are featured by micrometer needle arrays with an overall size in the centimeter scale. Due to the needle shape and the micron size, microneedles can penetrate the skin without harming nerves and blood vessels, which causes many advantages such as minimally invasive, safe and convenient. The past few decades have witnessed a great leap in microneedles research. The main materials of microneedles have changed from metal and ceramic to polymers with more complex functions, and the optimization of materials and preparation strategies has led to a greater variety of microneedle styles. Among them, the construction or combination of smaller size structures or materials on microneedles to fabricate hierarchical microneedles is a major research hotspot. Here, we present the recent research progress of hierarchical microneedles for biomedicine. We begin by discussing the fabrication strategies of hierarchical microneedles, including mainstream casting and coating methods based on microneedle molds and three dimensions (3D) printing methods. We then expand the discussion from the hierarchical microneedles with porous structure to those composited with nanomaterials. Eventually, we have a discussion about the research progress of hierarchical microneedles in the area of biomarkers detection and transdermal drug delivery, as well as its future development direction.

Osteoporosis (OP) is an age-related disease of bone metabolism, characterized by bone mass loss and bone microarchitecture deterioration, the poor osteogenesis microenvironment of OP caused hardly repairing of the bone defects. As a dynamic process to fuel cellular renovation, autophagy has been proved to play a vital role in regulating cell differentiation and maintaining bone homeostasis. Traditional bone repairing biomaterials are hardly repairing the bone defects under OP pathological microenvironment. Therefore, it is essential to development novel biomaterials to improve osteoporotic osteogenesis. Compared to biochemical cues, biophysical cues exhibited more advantages in biocompatible and side effects. Herein, inspired by the importance of enhanced autophagic response in osteoporotic environment, we intend to utilize the micro-/nano-structured hydroxyapatite (mnHA) bioceramics as the mimic structure of natural bone tissue to regulate autophagic activity in ovariectomy bone mesenchymal stem cells (OVX-BMSCs), finally promote to bone regeneration in OP condition. The results indicated that mnHA bioceramics promoted cell adhesion and osteogenesis of OVX-BMSCs, and enhanced autophagy level in OVX-BMSCs. In the calvarial defects of OVX-rats, the mnHA scaffold acquired excellent bone repair effect. According to the current findings, regulating the level of autophagy could be a promising strategy for improve osteoporotic osteogenesis in the future.

Patients with brain injury can suffer disability and accompanying complications. Current clinical treatments have significant limitations to successful repair due to the complexity of the pathological processes and the inhibitory microenvironment that follows brain injury. Here, we conclude recent research progresses in engineering strategies based on electrospun nanofibers for promoting neural repair and functional recovery after brain injury. Firstly, we introduce the main pathological mechanisms of current brain injuries, pointing out the prospect of the application of electrospun nanofiber scaffolds compared to current clinical treatment strategies. We then discuss the repair strategies combining the structure and the morphology of nanofiber scaffolds with load therapeutic factors such as cells, drugs and growth factors. All of these strategies show potential for improving the repair of brain injury. Finally, we point out the challenges facing the effective treatment of brain injury, aiming to provide insights into the development of repairing scaffolds for brain function recovery from the perspective of clinical treatment.

Infections at the placement site of biomaterial-based devices and subsequent scar formation results in morbidity, which may require revision surgery. Biomaterials intended for permanent implantation in the body need to be biologically inert to avoid excessive foreign body response and to reduce bacterial attachment. In this study, we show that polymeric materials commonly used in medical devices, including polyetheretherketone (PEEK) and polypropylene, treated by gas cluster ion beam (GCIB) or by accelerated neutral atom beam (ANAB) result in a nanoscale-modified surface topography that changes the ability of extracellular proteins to bind. This leads to decreased bacterial attachment and an attenuated inflammatory response using both in vitro and in vivo assays. Differential adsorption of extracellular proteins to the polymeric surface improved the competitive attachment of osteoblasts over bacteria, without resorting to growth factor of antibiotic use.

Angiogenesis—the formation of new blood vessels from existing blood vessels—has drawn significant attention in medical research. New techniques have been developed to control proangiogenic factors to obtain desired effects. Two important research areas are 1) understanding cellular mechanisms and signaling pathways involved in angiogenesis and 2) discovering new biomaterials and nanomaterials with proangiogenic effects. This paper reviews recent developments in controlling angiogenesis in the context of regenerative medicine and wound healing. We focus on novel proangiogenic materials that will advance the field of regenerative medicine. Specifically, we mainly focus on metal nanomaterials. We also discuss novel technologies developed to carry these proangiogenic inorganic molecules efficiently to target sites. We offer a comprehensive overview by combining existing knowledge regarding metal nanomaterials with novel developments that are still being refined to identify new nanomaterials.

The microenvironment of the wound bed is essential in the regulation of wound repair. In this regard, strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes. Herein, we attempted to use electrical stimulation (ES) to boost the paracrine function of adipose-derived stem cells from rats (rASCs). By examining the concentrations of two important growth factors, VEGF and PDGF-AA, in the cell culture supernatant, we found that ES, especially 5 μA ES, stimulated rASCs to produce more paracrine factors (5 μA-PFs). Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3, thereby inducing intracellular Ca²⁺ influx. To deliver the PFs to the wound to effectively improve the wound microenvironment, we prepared a heparinized PGA host-guest hydrogel (PGA-Hp hydrogel). Moreover, PGA-Hp hydrogel loaded with 5 μA-PFs effectively accelerated the repair process of the full-thickness wound model in rats. Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-guest hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.

Sensory hair cells (HCs) in the cochlea cannot regenerate spontaneously in adult mammals after being damaged by external or genetic factors. However, several genes and signaling pathways are reported to induce cochlear HC regeneration at the early neonatal stage. Rps14 encodes a ribosomal protein that is involved in the regulation of cell differentiation and proliferation in mammals. However, its roles in the cochlea have not been reported in vivo. Here, we specifically overexpressed Rps14 in Lgr5+ progenitor cells in the newborn mouse cochlea and found that Rps14 conditional overexpression (cOE) mice had significantly increased the ectopic HCs, including inner and outer HCs. We further explored the source of these ectopic HCs and found no EdU+ supporting cells observed in the Rps14 cOE mice. The lineage tracing results, on the other hand, revealed that Rps14 cOE mice had significantly more tdTomato+ HCs in their cochleae than control mice. These results indicated that regenerated HCs by cOE of Rps14 are most likely derived from inducing the direct trans-differentiation of Lgr5+ progenitor cells into HCs. Moreover, real-time qPCR results suggested that the transcription factor genes Atoh1 and Gfi1, which are important in regulating HC differentiation, were upregulated in the cochlear basilar membrane of Rps14 cOE mice. In summary, this study provides in vivo evidence that, in the postnatal mouse cochlea, Rps14 is a potential gene that can promote the spontaneous trans-differentiation of Lgr5+ progenitor cells into HCs. This gene may one day be exploited as a therapeutic target for treating hearing loss.