Engineered regeneration最新文献

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.

Micro-robots (MRs) are miniature machines with dimensions smaller than 1 mm and have semi- or fully-autonomous capabilities, including sensing, decision-making, and performing operations. These MRs have garnered significant attention in the precision medicine and personalized treatment field due to their ability to navigate narrow areas of the human body with non-desirable fluid flow. Specifically, MRs are actuated by a mechanism that generates propulsive force through the interaction between MRs' actuation modules and external energy sources in a specific direction. This driving mechanism enables the precise execution of medical treatment such as targeted drug delivery and minimally invasive surgeries. Nonetheless, MRs currently encounter certain challenges in clinical practice, including reliance on external energy sources, short lifespan, and difficulties in degradation or recovery within the human body. This article aims to review the common components and characteristics of driving mechanism for MRs' actuation modules, propose possible solutions to address current clinical challenges, and ultimately, explore the desirable structural and functional composition for the future development of MRs. Through these efforts, this review hopes to provide guidance for the future development of MRs in the field of precision medicine.

The extrusion-based bioprinting (EBBP) applications in the medical field tremendously increase due to its versatility in fabricating intricate geometry components with reasonable accuracy and precision. The bioink and its properties for an EBBP process are crucial in manufacturing parts with significant biocompatibility and functionality. The EBBP demands optimized parameters for obtaining good printability and cell viability. A better understanding of the various process parameters is essential for the researcher to optimize the mechanical and biological properties of the printed constructs. The biological, mechanical, and rheological parameters all together need to be evaluated to enhance the printability of tissue. This article concisely delineates the effect of the rheological and physiochemical parameters on the biological and mechanical properties of the printed tissues. The printing parameters and nozzle geometry, which considerably influence the printability, and shape fidelity of the bioprinted scaffolds are exemplified in detail. Additionally, the challenges and future aspects of enhancing printability are discussed succinctly.

Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels. Nevertheless, the mechanism responsible for this dynamic insulin secretion has not been completely understood, particularly at the single islet level. In this study, we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion (GSIS) at the single islet level. With the utilization of this platform, we evaluated dynamic GSIS from single islets isolated from both normal and diabetic rats. Our results demonstrate that islets can be categorized into three types based on their dynamic GSIS: Type I exhibits a biphasic GSIS profile with a fast first phase and flat second phase; Type II also has a biphasic GSIS profile with a fast first phase but a slow increased second phase; Type III displays only a slowly increased second phase and lacks a fast first phase. RNA sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets, respectively. Moreover, our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin secretion. Furthermore, we revealed that diabetic islets exhibit only the type I GSIS response, indicating a deliberate impairment of the second phase of insulin secretion. Together, this device serves as a crucial tool in the research field of islets and diabetes, allowing researchers to investigate islet functional heterogeneity and identity at the single islet level.