Regenerative Biomaterials最新文献

Triple-negative breast cancer (TNBC) has emerged as one of the dreadful metastatic tumors in women due to complexity, specificity and high recurrence, resulting in poor therapeutic outcomes and requiring real-time monitoring for improved theranostics. Despite the success as efficient radiosensitizers and computed tomography (CT)-based contrast agents, bismuth (Bi)-based composites suffer from poor colloidal stability, dose-dependent toxicity and pharmacokinetic shortcomings, leading to poor therapeutic monitoring. In addition, several small molecule-based therapeutics, including nanoparticle-based delivery systems, suffer from several limitations of poor therapeutic delivery and acquired multidrug resistance by cancer cells, depriving the therapeutic needs. To overcome this aspect, this study demonstrates the fabrication of drug-like/drugless nanoarchitectures based on copper sulfide-nanoplated bismuth oxide (Bi₂O₃@CuS, shortly BC) composites for improved theranostic efficacy against TNBC. These systematically characterized BC nanocomposites exhibited pH-/near-infrared (NIR, 808 nm) light-responsive degradability toward dual modal therapies. Due to the band transition of Cu species, the designed BC composites displayed exceptional photothermal (PTT) conversion efficiency toward localized PTT effects. In addition to pH-/NIR-responsiveness, the internally overexpressed glutathione (GSH)-responsiveness facilitated the release of Cu²⁺ species for chemodynamic therapy (CDT)-based effects. To this end, the Bi³⁺ species in the core could be fully hydrated in the acidic tumor microenvironment, resulting in GSH depletion and reducing CDT-induced reactive oxygen species clearance, thereby ablating tumors. The acid-responsive degradability of CuS resulted in the intratumoral enrichment of BC, demonstrating remarkable CT imaging efficacy in vivo. Together, these pH-/NIR-/GSH-responsive biodegradable BC composites could realize the integrated PTT/CDT/CT theranostics against breast carcinoma.

Gold nanoparticles have recently been exploited as versatile nanocarriers in diagnostic and therapeutic drug delivery for cancer nanomedicine, owing to their biocompatibility, low biotoxicity, surface modifiability and plasma optical properties. A variety of gold nanoparticles have emerged for drug delivery, mainly including gold nanorods, gold nanocages, gold nanostars, gold solid nanospheres and hollow gold nanospheres (HGNs). Among these, HGNs have widely been studied for their higher photothermal conversion efficiency, wider spectral absorption range and stronger surface-enhanced Raman scattering compared with solid gold nanospheres. Therefore, nowadays, researchers prefer to use HGNs to other metal nanocarriers, which can not only play the role of controlled-release drugs but also act as photothermal agents for tumor therapy and diagnosis, due to their properties of surface modification. Combined with the Au-S bond on the surface of HGNs, the targeted preparation is loaded to achieve precise drug delivery. With the assistance of the photothermal characteristics of HGNs themselves, the efficacy of loaded drugs in HGNs is enhanced. In addition, HGNs also have vital values in the field of bioimaging, which serve as photothermal imaging agents and Raman scattering-guided preparations due to their surface-enhanced Raman scattering properties to assist researchers in achieving the purpose of tumor diagnosis. In this review, we summarize the synthesis methods of HGNs and the recent application of HGNs-based nanomaterials in the field of cancer diagnosis and therapy. In addition, the issues to be addressed were pointed out for a bright prospect of HGNs-based nanomaterials.

Decellularized organs and tissues are emerging within the field of regenerative medicine to meet the growing demand for organ and tissue transplantation. Quality control of these acellular matrices prior to transplantation is of paramount importance to ensure the absence of an adverse reaction. In particular, thorough evaluation of the DNA content is essential but also poses technical challenges. Therefore, in this study, we compared different methods for quantitative and qualitative evaluation of DNA content in native and decellularized skeletal muscle tissue to identify strengths and weaknesses for each. Histological analysis revealed that Feulgen staining is more sensitive and robust than the commonly used hematoxylin-eosin and 4',6-diamidino-2-phenylindole staining for detection of remaining nuclear material. Furthermore, gel electrophoresis allowed to identify the quality and length of remaining DNA fragments. The results of the quantitative analysis indicated that direct measurement of DNA content in tissue lysates is preferred over silica-based extraction methods, since the latter resulted in the loss of small DNA fragments during extraction. Moreover, a weight loss correction factor should be implemented to take into account the impact of the decellularization on the extracellular matrix. With regard to the detection method, the results revealed that a fluorescence-based approach is more accurate than the use of UV/VIS absorbance. Through combination of the proposed methods, it should be possible to achieve a more standardized evaluation of novel acellular matrices in terms of DNA content and to enhance the predictability of clinical success.

Currently, generalized therapy for traumatic optic neuropathy (TON) is lacking. Various strategies have been developed to protect and regenerate retinal ganglion cells (RGCs) after TON. Intravitreal injection of supplements has been approved as a promising approach, although serious concerns, such as low delivery efficacy and pain due to frequent injections, remain. In this study, we tested an injectable thermosensitive hydrogel drug delivery system engineered to deliver ciliary neurotrophic factor (CNTF) and triamcinolone acetonide (TA). The results of rheological studies showed that the prepared drug-loaded hydrogel possessed a suitable mechanical modulus of ∼300 Pa, consistent with that of vitreum. The hydrogel exhibited thermosensitive with sustained drug release performance. In vitro co-culture of the CNTF-loaded hydrogel system with primary RGCs also induced significant axon regeneration, with 38.5% increase in neurite length, indicating the regenerative response of the thermosensitive hydrogel drug delivery system. A Sprague-Dawley rat optic nerve crush model was constructed and applied to determine the neuroprotective and regenerative capacities of the system. The results demonstrated that a single intravitreal injection of the drug-loaded hydrogel (PLGA-PEG-PLGA + TA or PLGA-PEG-PLGA + CNTF) significantly increased RGC survival at both 14 and 28 days. The RGC survival rate was 31.05 ± 1.41% for the drug-loaded hydrogel system (the control group was 16.79 ± 1.50%) at Day 28. These findings suggest that the injectable drug-loaded thermosensitive hydrogel delivery system is a promising therapeutic tool for treating optic nerve degeneration.

The management of full-thickness skin injuries continues to pose significant challenges. Currently, there is a dearth of comprehensive dressings capable of integrating all stages of wound healing to spatiotemporally regulate biological processes following full-thickness skin injuries. In this study, we report the synthesis of a dandelion-shaped mesoporous strontium-gallium microparticle (GE@SrTPP) achieved through dopamine-mediated strontium ion biomineralization and self-assembly, followed by functionalization with gallium metal polyphenol networks. As a multifunctional wound dressing, GE@SrTPP can release bioactive ions in a spatiotemporal manner akin to dandelion seeds. During the early stages of wound healing, GE@SrTPP demonstrates rapid and effective hemostatic performance while also exhibiting antibacterial properties. In the inflammatory phase, GE@SrTPP promotes M2 polarization of macrophages, suppresses the expression of pro-inflammatory factors, and decreases oxidative stress in wounds. Subsequently, during the stages of proliferation and tissue remodeling, GE@SrTPP facilitates angiogenesis through the activation of the Hypoxia-inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway. Analogous to the dispersion and rooting of dandelion seeds, the root-like new blood vessels supply essential nutrients for wound healing. Ultimately, in a rat chronic wound model, GE@SrTPP achieved successful full-thickness wound repair. In summary, these dandelion-shaped GE@SrTPP microparticles demonstrate comprehensive regulatory effects in managing full-thickness wounds, making them highly promising materials for clinical applications.

[This corrects the article DOI: 10.1093/rb/rbae105.].

Natural remedies are gaining attention as promising approaches to alleviating inflammation, yet their full potential is often limited by challenges such as poor bioavailability and suboptimal therapeutic effects. To overcome these limitations, we have developed a novel nano-antioxidant (EK) based on epigallocatechin gallate (EGCG) aimed at enhancing the oral and systemic bioavailability, as well as the anti-inflammatory efficacy, of curcumin (Cur) in conditions such as acute colon and kidney inflammation. EK is synthesized using a straightforward Mannich reaction between EGCG and L-lysine (K), resulting in the formation of EGCG oligomers. These oligomers spontaneously self-assemble into nanoparticles with a spherical morphology and an average diameter of approximately 160 nm. In vitro studies reveal that EK nanoparticles exhibit remarkable radical-scavenging capabilities and effectively regulate redox processes within macrophages, a key component in the body's inflammatory response. By efficiently encapsulating curcumin within these EK nanoparticles, we create Cur@EK, a formulation that demonstrates a synergistic anti-inflammatory effect. Specifically, Cur@EK significantly reduces the levels of pro-inflammatory cytokines TNF-α and IL-6 while increasing the anti-inflammatory cytokine IL-10 in lipopolysaccharide-stimulated macrophages, highlighting its potent anti-inflammatory properties. When administered either orally or intravenously, Cur@EK shows superior bioavailability compared to free curcumin and exhibits pronounced anti-inflammatory effects in mouse models of ulcerative colitis and acute kidney injury. These findings suggest that the EK nano-antioxidant platform not only enhances the bioavailability of curcumin but also amplifies its therapeutic impact, offering a promising new avenue for the treatment and management of inflammation in both oral and systemic contexts.

Enhanced computed tomography (CT) imaging with iodinated imaging probes is widely utilized for the diagnosis and evaluation of various liver diseases. However, these iodine-based imaging probes face intractable limitations including allergic reactions and contraindications. Herein, we propose the utilization of renal-clearable iodine-free bismuth chelate (Bi-DTPA dimeglumine) for the non-invasive fast assessment of hepatic ischemia-reperfusion injury (HIRI) via CT imaging for the first time. Bi-DTPA dimeglumine offers several advantages such as simple synthesis, no purification requirement, a yield approaching 100%, large-scale production capability (laboratory synthesis > 100 g), excellent biocompatibility and superior CT imaging performance. In a normal rat model, the administration of Bi-DTPA dimeglumine resulted in a significant 63.79% increase in liver CT value within a very short time period (30 s). Furthermore, in a HIRI rat model, Bi-DTPA dimeglumine enabled the rapid differentiation between healthy and injured areas based on the notable disparity in liver CT values as early as 15 min post-reperfusion, which showed a strong correlation with the histopathological analysis results. Additionally, Bi-DTPA dimeglumine can be almost eliminated from the body via the kidneys within 24 h. As an inherently advantageous alternative to iodinated imaging probes, Bi-DTPA dimeglumine exhibits promising prospects for application in liver disease diagnosis.

As a well-known natural protein biomaterial, silk fibroin (SF) has shown broad application prospects in typical biomedical fields. However, the mostly used SF from Bombyx mori silkworm lacks specific cell adhesion sites and other bioactive peptide sequences, and there is still significant room for further improvement of their biological functions. Therefore, it is crucial to develop a facile and effective modification strategy for this widely researched biomaterial. In this study, the SF electrospun scaffold has been chosen as a typical SF biomaterial, and air plasma etching has been adopted as a facile nanopattern modification strategy to promote its biological functions. Results demonstrated that the plasma etching could feasibly and effectively create nano-island-like patterns on the complex surface of SF scaffolds, and the detailed nanopattern features could be easily regulated by adjusting the etching time. In addition, the mesenchymal stem cell responses have illustrated that the nanopattern modification could significantly regulate corresponding cell behaviors. Compared with the non-etched scaffold, the 10 min-etched scaffolds (10E scaffold) significantly promoted stem cell proliferation and osteogenic differentiation. Moreover, 10E scaffold has also been confirmed to effectively accelerate vascularization and ectopic osteogenesis in vivo using a rat subcutaneous implantation model. However, the mentioned promoting effects would be weakened or even counteracted with the increase of etching time. In conclusion, this facile modification strategy demonstrated great application potential for promoting cell proliferation and differentiation. Thus, it provided useful guidance to develop excellent SF-based scaffolds suitable for bone and other tissue engineering.

Poor wound healing in diabetics is primarily caused by persistently high levels of inflammation and recurrent bacterial infections. The catalytic therapy technique based on nanozyme medicine has emerged as a beacon of hope for patients with diabetic wounds. However, the use of a single-atom nanozyme may still have limitations, including nanozyme burst release, immunological clearance and insufficient antibacterial activity. To address the aforementioned problems, we provide a new nano-catalytic therapeutic agent for diabetic skin ulcers that incorporates a single-atom nanozyme with high antioxidant activity into a metal-organic framework (ZIF-Cu/C-dots). First, a Cu single-atom nanozyme supported by ultra-small carbon dots (Cu/C-dots) with high antioxidant activity was created. A nanozyme-integrated metal-organic framework was then created, utilizing Cu/C-dots as ligands and Zn²⁺ as the core metal. Cu/C-dots have good oxidase-like activity, shielding the biological system from ROS damage and reducing the expression of TNF-α and IL-1β. Zn²⁺ also has good antibacterial activity (the antibacterial rate was more than 90%). This integrated technique prevents nanozyme aggregation, improves nanozyme biocompatibility, slows down the breakdown of ZIF and allows for the regulated release of Cu/C-dots and Zn²⁺ as needed. Finally, in vivo studies have shown that ZIF-Cu/C-dots can effectively alleviate inflammation at the site of diabetic wounds, accelerate vascular regeneration, promote collagen deposition and enhance tissue remodeling, serving as a novel nano-catalytic platform for the treatment of wounds that are difficult to heal.