Engineered regeneration最新文献

As a hallmark of skin aging, senescent human dermal fibroblasts (HDFs) are known to lose the ability to divide. However, they can still interact with their cellular environment and the surrounding matrix. As the skin ages, the progressive slowing down of HDFs function decreases the skin's structural integrity, which is more serious than if there is the dermal collagen matrix eroded. This leads to matters of the unbalanced barrier under the skin, skin fragility, inadequate wound healing, as well as other cosmetic issues. It is also well documented that skin aging comes with significant stiffness increases. Therefore, understanding the interactions between HDFs and the surrounding microenvironments during senescence may provide insights into skin aging. Here we aim to investigate matrix stiffness' effect on HDF senescence and elucidate possible mechanisms that make HDFs senescent. In our experiments, HDFs were cultivated on Polydimethylsiloxane (PDMS) with various stiffnesses and exposed to UV light to trigger senescence. Results show that HDFs are significantly affected by senescence when cultured on a matrix with stiffness. However, the cells are not significantly affected when cultured on a low stiffness matrix. The following characterization revealed cells cultured on stiff substrates under UV exposure had stimulated the nucleus factor kappa-B (NF-κB) activation. In contrast, cells on a matrix of softness only displayed low activation of NF-κB. NF-κB activity suppression with ammonium pyrrolidine dithiocarbamate (PDTC) decreases UV-induced HDFs senescence on stiff substrates. Taken together, we demonstrated that soft matrix defends HDFs against ultraviolet-induced senescence by inhibiting the activation of NF-κB.

Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure. The native microenvironment of the bone tissue may be significantly disrupted by large physiological and pathological bone defects. Bone defects are often treated via complex surgical procedures that involve the application of autografts or allografts. While these grafting procedures often suffer from insufficient natural bone stock and immunorejection. Moreover, these traditional treatment methods fail to simulate a regenerative microenvironment, which plays a significant role in regeneration of bone tissue and repair of large bone defects. To this end, various biomimetic scaffolds have been devised to mimic the native microenvironment of bone and thereby to simultaneously repair bone defects and promote bone regeneration. We propose here a novel concept, in vivo bone regenerative microenvironment (BRM), which enables repair of large bone defects and enhances new bone tissue formation with external regulation. In this review, we mainly focus on materials and methods for fabrication of biomimetic scaffolds, as well as their therapeutic efficacy in modulating the BRM of large physiological and pathological bone defects.

Mitral valve (MV) tissue engineering is still in its early stage, and one major challenge in MV tissue engineering is to identify appropriate scaffold materials. With the potential of acellular MV scaffolds being demonstrated recently, it is important to have a full understanding of the biomechanics of the native MV components and their acellular scaffolds. In this study, we have successfully characterized the structural and mechanical properties of porcine MV components, including anterior leaflet (AL), posterior leaflet (PL), strut chordae, and basal chordae, before and after decellularization. Quantitative DNA assay showed more than 90% reduction in DNA content, and Griffonia simplicifolia (GS) lectin immunohistochemistry confirmed the complete lack of porcine α-Gal antigen in the acellular MV components. In the acellular AL and PL, the atrialis, spongiosa, and fibrosa trilayered structure, along with its ECM constitutes, i.e., collagen fibers, elastin fibers, and portion of GAGs, were preserved. Nevertheless, the ECM of both AL and PL experienced a certain degree of disruption, exhibiting a less dense, porous ECM morphology. The overall anatomical morphology of the strut and basal chordae were also maintained after decellularization, with longitudinal morphology experiencing minimum disruption, but the cross-sectional morphology exhibiting evenly-distributed porous structure. In the acellular AL and PL, the nonlinear anisotropic biaxial mechanical behavior was overall preserved; however, uniaxial tensile tests showed that the removal of cellular content and the disruption of structural ECM did result in small decreases in maximum tensile modulus, tissue extensibility, failure stress, and failure strain for both MV leaflets and chordae.

The osteogenic differentiation and new bone formation are commonly delayed by bacterial infection of orthopedic implants, which is urgent to be resolved quickly in the clinic. The current paper prepared a strontium-doped electrospinning fiber membrane with antibacterial and osteogenic properties by pulse electrochemical method. Polylactic acid/hydroxyapatite (PLLA/HA) composite fiber substrate was fabricated by electrospinning technology, and strontium doped SrHA/Cu/Polypyrrole (PPy) composite coating was constructed with pulse electrodeposition method on its surface. The strontium doping technique, degradation of Sr²⁺ and Cu²⁺, cellular compatibility, and the antibacterial activity of the fiber membrane were examined. The results revealed that the deposition of phosphorus and calcium on composite fiber was the highest, indicating good biological activity. The release of Sr²⁺ and Cu²⁺ was stable and gradual due to the modulation of PPy. The composite fiber presented excellent antibacterial performance and the antibacterial rate was close to 100% against Staphylococcus aureus and Escherichia coli. Furthermore, it is conducive to the adhesion, spread, and proliferation of vascular endothelial cells and osteoblasts, namely outstanding osteogenesis and angiogenesis abilities. In conclusion, the multifunctional PLLA/HA@SrHA/Cu/PPy composite fiber membrane with good antibacterial and osteogenic activity by electrospinning technology and pulsed electrochemical deposition method provides an effective strategy for the poor bone healing of infected bone defects.

We developed a reliable simple analysis of adenosine, creatinine and other nucleosides (cytidine and guanosine) with single measurement based on surface-enhanced Raman spectroscopy (SERS) using DSP-AuNPs with Cu²⁺ ions probe and applied it to achieve noninvasive screening of lung cancer. The gold nanoparticles (AuNPs) were modified with 3,3′-dithiodipropionic acid di (N-hydroxysuccinimide ester) (DSP), which could react with above mentioned molecules followed with the aggregation of AuNPs at the presence of Cu²⁺, thus form the plasmonic hot spots to dramatically increase their fingerprint Raman signal. The probe of DSP-AuNPs was applied for the detail analysis of urinary adenosine of healthy people and lung cancer patients. The SERS measurement indicated a higher concentration of urinary adenosine for lung cancer patients than that of healthy people, which was consistent with the results measured by high-performance liquid chromatography (HPLC). In combination of Raman spectroscopy with the orthogonal partial least squares discriminant analysis (OPLS-DA) model, we are able to discriminate the lung cancer patients from healthy people with the urinary test. The results indicated that besides of adenosine, other metabolites including uric acid, guanine and creatinine may also be the potential tumor markers in urine for the noninvasive lung cancer diagnosis. Such a method paves a way for the noninvasive cancer screening and it can be further modified for the detection of other molecules on medical diagnosis.

The engineered biomimetic sensors can not only realize the action of organs, but also combine functional materials as in vitro organs by simulating the response of biological organs to different environmental signals. Artificial nose is a concept proposed by imitating biological olfactory system, simulating olfactory nerve cells, olfactory bulb and olfactory cortex through different materials to realize olfactory function. The sensor array used to sense external gas stimulation can be analyzed based on different recognition principles through different original signals such as optics, electricity, electrochemistry and bioelectricity. Furthermore, combined with pattern recognition and microarray technology, artificial nose can be highly integrated with biocompatible and other important properties to achieve in vitro application. The design principle and necessary components of artificial nose are introduced in this paper including sensing structure, recognition system and functional module. At the same time, the potential development prospects of molecular recognition technology, polymer-based materials and microarray integration in artificial nose are prospected.

Spinal cord injury (SCI) often causes severe functional impairment of body, which leads to a huge burden to the patient and the whole society. Many strategies, especially biomaterials, have been employed for SCI repair. Among various biomaterials, injectable hydrogels have attracted much attention because of their ability to load functional components and be injected into the lesioned area without surgeries. In this review, we summarize the recent progress in injectable hydrogels for SCI repair. We firstly introduce the pathophysiology of SCI, which reveals the mechanism of clinical manifestations and determines the therapeutic schedule. Then, we describe the original sources of polymers and the crosslinking manners in forming hydrogels. After that, we focus on the in vivo therapeutic strategies and effects of injectable hydrogels. Finally, the recent challenges and future outlook of injectable hydrogel for SCI repair are concluded and discussed. We believe this review can be helpful and inspire the further development of injectable hydrogels for SCI repair.

Adsorption or enrichment has been an indispensable and important measure in biomedical engineering since it is promising in diagnosis and treatment of complex diseases. The ongoing development in this arena starves for exploration of outstanding adsorptive materials. As an excellent candidate for adsorption or enrichment carriers, carbon-based material has demonstrated unique superiority in biomedical arena owing to its integrated characteristics. Herein, we review the lasted advance in adsorptive carbon-based materials for biomedical application with emphasis on carbon nanotubes (CNTs)-based, graphene-based, and biomass/polymer-based ones. We begin with the classification of different carbon-based materials and elaborate the respective preparation approaches that are utilized to realize optimized microstructure and physicochemical property. Afterwards, we introduce the different applications of carbon-based materials in biomedical arena, including blood purification, enrichment of glycopeptide and phosphopeptide, and breath analysis. Finally, we present a concise summary and give an outlook of this arena.

Acoustofluidics has been a promising approach using sound waves to manipulate particles and actuate fluids in biomedical applications. It usually generates acoustic radiation force and acoustic streaming to initiate diffraction, reflection and interference, building up a pressure distribution to facilitate accurate manipulation of micro- or nano-scale particles and fluids. Owing to its remarkable contact-free and biocompatible advantages, acoustofluidics has been used in high-throughput cell analysis, size-controllable organoid structures, and functional tissue mimics. We enumerate the basic concepts and the sufficient research of acoustofluidics in precise patterning and tissue engineering in this review, including the design and function of four typical acoustofluidic devices, various forms of cell patterning and 3D tissue engineering. Meanwhile, we outlined current challenges and future directions of acoustofluidics in biomedicine and tissue engineering.

Wearable biosensors, which aim at providing continuous, real-time physiological information via monitoring and screening biomarkers in human body, are receiving increasing attention among various fields including disease treatment, diagnosis and self-health management. The ongoing development in this realm starves for the exploration of fully-integrated, non-invasive devices. In this paper, we review the latest achievements with breakthrough significance on the wearable biosensors. We start with the classification of different types of wearable electronic devices and analyze their characteristics and application values. Subsequently, we introduce a fully-integrated microneedle-based sensor and provide an in-depth look at its structure, subcomponents and in vivo performances. Finally, we put forward critical commentaries and clarify the direction of future researches.