To address the high viscosity and poor flowability of crude oil during heavy-oil cold production and waterflooding, as well as the high dosage requirement, insufficient interfacial adaptability, and limited viscosityreduction efficiency of existing nano-viscosity reducers, amphiphilic polydopamine nanoparticles (PDA@A12) were prepared using dopamine hydrochloride as the monomer and dodecylamine as the modifier through solution oxidative polymerization and Schiff-base reaction. Their structure, performance, and viscosity-reduction mechanism were systematically investigated. The results show that long alkyl chains of dodecylamine were successfully introduced onto the PDA surface, transforming PDA from a strongly hydrophilic material into an amphiphilic nanoparticle. PDA@A12 exhibited an average hydrodynamic diameter of 154.2 nm, and its contact angle increased from 33.7 degrees to 86.3 degrees. PDA@A12 effectively reduced the oil-water interfacial tension and stabilized O/W emulsions. At a concentration of 150 mg/L, the viscosity reduction efficiencies of PDA@A12 reached 91.9 % and 89.5 % at oil-to-water ratios of 2:8 and 3:7, respectively, indicating that it is more suitable for emulsification viscosity reduction of ordinary heavy oil under conditions where the aqueous phase is relatively abundant or continuous. The viscosity reduction by PDA@A12 is dominated by interfacial emulsification, supplemented by the disaggregation of asphaltene aggregates. Specifically, its surface polar groups, indole aromatic structures, and dodecylamine alkyl chains can weaken asphaltene lamellar stacking and association through hydrogen bonding, it-it competitive interactions, and hydrophobic-chain insertion, thereby improving the flowability of ordinary heavy oil. This study provides a new amphiphilic organic nanomaterial strategy for the design of viscosity-reduction systems for ordinary heavy oil.

Silicone-based implants have been widely used in breast reconstruction but have also been associated with poorly understood complications, including pathologic foreign body responses such as capsular contracture. In this study, we leveraged 3D-printing technology to generate silicone-based implants in a novel, anatomically relevant, prepectoral rat model. We used this model to evaluate the response to an extracellular matrix-based product: ovine-derived reinforced tissue matrix (RTM). Two-piece negative molds were developed through computer-aided design and 3D-printed. The molds were filled with various polydimethylsiloxane mixtures and dip-coated to fabricate implants. Implant material characterization revealed that the implants retained the original 3D-printed mold shape and qualitatively demonstrated a shell with an inner solid gel-like structure. Fabricated implants had smooth surfaces, as well as tunable features including implant stiffness (storage modulus). From initial studies in our rat model, placement of bilateral prepectoral implants allowed assessment of both muscle- and skin-facing capsules and were well-tolerated for at least 12 weeks. Comparison of the foreign body response between RTM-covered and uncovered (control) implants in this model revealed that the capsule thickness did not differ between groups at the 12-week endpoint. However, RTM reduced contractile fibroblasts (alpha-smooth muscle actin) and macrophages (Iba1) compared to the control. Our findings suggested that RTM may improve capsule quality by attenuating cells involved in fibrosis, even when total capsule thickness remains unchanged. However, these changes to cells involved in fibrosis were only observed at this early endpoint and may not predict long-term clinical outcomes.

Peripheral arterial disease (PAD) is a progressive atherosclerotic disorder that reduces blood flow to the lower extremities, leading to skeletal muscle degeneration, functional decline, and limb loss in advanced stages. To enable rigorous preclinical evaluation of regenerative therapies across disease stages, we developed and quantitatively characterized three rat hindlimb ischemia models representing graded arterial insufficiency: iliac artery ligation (Iliac), femoral artery ligation and excision (Femoral), and combined femoral plus popliteal artery ligation and excision (Fem/Pop). Laser Doppler perfusion imaging demonstrated an immediate reduction to approximately 60–65% of baseline in Iliac, 40–50% in Femoral, and less than 30% in Fem/Pop limbs. Perfusion recovery occurred earliest in the Iliac model, with delayed recovery in the Femoral and Fem/Pop models, while overall temporal recovery trends were comparable by mixed-effects analysis. Histological and quantitative morphometric analyses at the chronic endpoint revealed progressively severe muscle remodeling with increasing ischemic burden, including increased centrally nucleated fibers and fibrosis, most pronounced in the Fem/Pop model. Oxidative stress markers trended higher with increasing ischemia severity but did not differ significantly among models. Among the three models, Fem/Pop produced the most sustained clinical ischemia and structural remodeling, while regenerative, inflammatory, and biochemical endpoints exhibit heterogeneity at chronic stages, enabling stage-appropriate evaluation of vascular and regenerative therapeutic strategies.

Spinal cord injury (SCI) is a neurological disorder, with neuronal oxidative and inflammatory damage being the key pathogenic mechanisms. The essential trace element selenium (Se) exerts anti-inflammatory and anti-oxidant neuroprotective effects primarily by regulating selenoproteins, demonstrating great potential in SCI neuroprotective therapy. Herein, we found that the damage of spinal cord tissue leads to acute-phase depletion of endogenous selenoprotein, and Se supplementation, especially selenomethionine (SeM), can exert a neuroprotective effect. We further developed a lipid nanoparticles (LNP) encapsulation system for SeM delivery (SeM@LNP) to enhance its blood circulation time and biological utilization rate, thereby facilitating its penetration through the blood-spinal cord barrier (BSCB) and accumulation in the spinal cord. SeM@LNP effectively scavenges glucose-oxygen deprivation (OGD)-induced excessive reactive oxygen species (ROS) accumulation in neurons via upregulating the expression of antioxidative selenoproteins, thereby regulating mitochondrial fission and fusion by activating the AMPK-MFN1/OPA1-Drp1 axis to maintain mitochondrial morphology, function and energy metabolism. Furthermore, SeM@LNP suppresses microglia activation and reduces pro-inflammatory factor levels to mitigate neuroinflammation, then exhibits synergistic anti-oxidant and anti-inflammatory activity in vivo, effectively alleviating nervous impairment. These findings highlight SeM@LNP as a potential nanotherapeutic platform for SCI, and elucidate its dual anti-inflammatory and antioxidant mechanisms in mitigating secondary damage cascades post-SCI.

Periodontal regeneration remains challenging due to individual variability, especially in treatments involving bioactive factors such as metformin. This study aimed to investigate the role of organic cation transporters (OCTs) in metformin-induced periodontal regeneration. The expression and function of OCTs in human periodontal ligament stem cells (hPDLSCs) were assessed, and OCT-mediated metformin uptake was quantified by high-performance liquid chromatography (HPLC). Osteogenic and cementogenic differentiation markers were analyzed in vitro, and periodontal regeneration was evaluated using a rat periodontal defect model. OCTs were differentially expressed and functional in hPDLSCs. Both the OCT1 inhibitor cimetidine and OCT1 knockdown significantly reduced intracellular metformin accumulation to 50–60% and 20–30% of control levels, respectively (p < 0.01). Cimetidine diminished the osteogenic and cementogenic effects of metformin by approximately 31–48% and 32–40%, respectively (p < 0.01). In vivo, oral administration of cimetidine decreased bone regeneration by 25% and cementum regeneration by 36% compared with controls receiving GelMA/hPDLSCs/metformin (p < 0.01). This study demonstrates that OCTs regulate metformin uptake in hPDLSCs, and that inhibition of OCT1 by cimetidine significantly reduces the osteogenic and cementogenic efficacy of metformin, providing the first evidence of drug interactions affecting periodontal regeneration mediated by OCT transport in rats.

Arteriovenous fistulas (AVFs) are the gold standard for vascular access to facilitate hemodialysis, yet traditional surgical techniques are technically demanding, time-intensive, and costly. Additionally, limited suitable AVF sites, due to patient anatomy, vessel quality, and prior access exhaustion, necessitate exploration of novel options. This cadaveric proof-of-concept study introduces the anterior interosseous artery-cephalic vein as a novel AVF site and evaluates the feasibility of a 3D-printed sutureless anastomotic device, the Vaso-Stent, compared to conventional handsewn techniques. Fresh-frozen cadaveric upper limbs were procured to test the surgical feasibility of the proposed AVF model. Surgical exposure of the interosseous artery and adjacent cephalic vein were uncomplicated. A 3D-printed Vaso-Stent was manufactured and facilitated efficient anastomosis in under 1 min, compared with the 4.5 min required for a standard handsewn technique. The device demonstrated ease of placement, robust structural integrity, and resistance to tensile forces. These findings highlight that the Vaso-Stent can provide a simple alternative for AVF creation that reduces operative time and highlight the anterior interosseous artery-cephalic vein configuration as a new and unique hemodialysis access opportunity.

Spinal cord injury (SCI) is a critical condition affecting the central nervous system that often has permanent and debilitating consequences, including secondary injuries. Oxidative damage and inflammation are critical factors in secondary pathological processes. Selenium nanoparticles have demonstrated significant antioxidative and anti-inflammatory properties via a non-immunosuppressive pathway; however, their clinical application has been limited by their inadequate stability and functionality to cross the blood-spinal cord barrier (BSCB). This study proposed a synthesis method for ultra-small-diameter lentinan Se nanoparticles (LNT-UsSeNPs) with significantly superior reactive oxygen species (ROS) scavenging capabilities compared to conventional lentinan Se nanoparticles (LNT-SeNPs). These compounds effectively protected PC-12 cells from oxidative stress-induced cytotoxicity, alleviated mitochondrial dysfunction, reduced apoptosis. In vivo studies indicated that LNT-UsSeNPs efficiently penetrated the BSCB and effectively inhibited the apoptosis of spinal neurons. Ultimately, LNT-UsSeNPs directly regulated the PI3K-AKT-mTOR and Ras-Raf-MEK-ERK signaling pathways by regulating selenoproteins to achieve non-immunosuppressive anti-inflammatory therapy. Owing to their ultra-small size, LNT-UsSeNPs exhibited strong spinal barrier penetration and potent antioxidative and anti-inflammatory effects without compromising immune function. These findings suggest that LNT-UsSeNPs are promising candidates for further development in nanomedicine for the effective treatment of SCI.

Peripheral nerve regeneration relies on repair Schwann cells (SCs) to support axonal regrowth and functional recovery. This study aimed to identify drugs that promote this repair phenotype, which is regulated by the expression of the transcription factor c-Jun. Purmorphamine (PUR) and Smoothened agonist (SAG) are both Sonic Hedgehog (SHH) agonists that have been implicated in promoting regeneration after neurological injury in animal models. Here, we have demonstrated that SHH agonists significantly increased c-Jun expression in rat primary SCs and promoted morphological and functional changes consistent with the repair SC phenotype, including an elongated bipolar morphology and increased secretion of neurotrophic factors. Notably, PUR consistently demonstrated a greater potency in driving these effects compared with SAG at the same concentrations. We also identified 2.5 µM PUR as an effective dosage producing these measurable effects in vitro. Coculturing dorsal root ganglion (DRG) neurons with PUR-treated SCs resulted in a marked increase in neurite elongation, suggesting that cell-based or contact-dependent features of repair SCs contribute to axon growth. These findings demonstrate that SHH agonists effectively reprogram SCs into a repair phenotype, which constitutes a potential therapeutic strategy for enhancing nerve regeneration and functional recovery in peripheral nerve injury treatment.

A vascular anastomosis is a critical surgical skill that involves connecting blood vessels. Traditional handsewn techniques can be challenging and resource intensive. To address these issues, we have developed a unique sutureless anastomotic device called Vaso-Lock. This intraluminal device connects free vascular ends using anchors to maintain traction and enable a rapid anastomosis. We tested the anastomotic capability of Vaso-Locks in a pig common carotid-internal jugular arteriovenous model. The use of Vaso-Lock allowed us to accomplish this procedure in less than 10 min, in contrast to the approximately 40 min required for a handsewn anastomosis. The Vaso-Lock effectively maintained patency for at least 6 weeks without causing significant tissue damage. Histological analysis revealed that the device was successfully incorporated into the arterial wall, promoting a natural healing process. Additionally, organ evaluations indicated no adverse effects from using the Vaso-Lock. Our findings support the safety and effectiveness of the Vaso-Lock for arteriovenous anastomosis in pigs, with potential applicability for translation to humans. Our novel sutureless device has the potential to advance surgical practice and improve patient outcomes.

Dilated Cardiomyopathy (DCM), a prevalent form of cardiomyopathy, is characterized by ventricular dilation and systolic dysfunction. Its etiology is intricate, encompassing multiple genetic and environmental elements. The LMOD2 (Leiomodin 2) gene has been demonstrated to be closely associated with the pathogenesis of DCM. In this study, a pure cell line was generated by knocking out the LMOD2 gene, and a DCM cell model was established through induced differentiation, thus providing a powerful experimental approach for further understanding the pathogenesis of DCM. It also provides a potential research orientation for the early diagnosis and individualized treatment of DCM.

Synthetic polymers are often utilized in the creation of vascular devices, and need to possess specific qualities to prevent thrombosis. Traditional strategies for this include surface modification of vascular devices through covalent attachment of substrates such as heparin, antiplatelet agents, thrombolytic agents, or hydrophilic polymers. One promising prosthetic material is polyether ether ketone (PEEK), which is utilized in various FDA-approved medical devices, including vascular and endovascular prostheses. We hypothesized that surface modification of biologically inert PEEK can help improve its endothelial cell affinity and reduce its thrombogenic potential. To evaluate this, we developed an effective surface-modification approach with unique cyclic peptides, such as CCHGGVRLYC and CCREDVC. We treated the PEEK surface with ammonia plasma, which introduced amine groups onto the PEEK surface. Subsequently, we were able to conjugate these peptides to the plasma-modified PEEKs. We observed that cyclic CCHGGVRLYC conjugated on prosthetic PEEK not only supported endothelialization, but minimized platelet adhesion and activation. This technology can be potentially applied for in vivo vascular and endovascular protheses to enhance their utility and patency.

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.

Sutureless anastomotic devices present several advantages over traditional suture anastomosis, including expanded global access to microvascular surgery, shorter operation and ischemic times, and reduced costs. However, their adaptation for arterial use remains a challenge. This review aims to provide a comprehensive overview of sutureless anastomotic approaches that are either FDA-approved or under investigation. These approaches include extraluminal couplers, intraluminal devices, and methods assisted by lasers or vacuums, with a particular emphasis on tissue adhesives. We analyze these devices for artery compatibility, material composition, potential for intimal damage, risks of thrombosis and restenosis, and complications arising from their deployment and maintenance. Additionally, we discuss the challenges faced in the development and clinical application of sutureless anastomotic techniques. Ideally, a sutureless anastomotic device or technique should eliminate the need for vessel eversion, mitigate thrombosis through either biodegradation or the release of antithrombotic drugs, and be easily deployable for broad use. The transformative potential of sutureless anastomotic approaches in microvascular surgery highlights the necessity for ongoing innovation to expand their applications and maximize their benefits.

The interplay between biomaterials and host immune responses critically determines outcomes in tissue restoration. Recent studies suggest that physicochemical properties of materials can dictate pro-regenerative versus pro-fibrotic responses and have begun to define the key immune cell types and signals governing these divergent effects. This emerging understanding enables the engineering of regenerative biomaterials capable of functional restoration in situ. An injectable nanofiber-hydrogel composite (NHC) microparticles are designed and constructed from cross-linked electrospun collagen nanofiber fragments surface-bonded to the hyaluronic acid hydrogel network via covalent conjugation during the cross-linking process. The collagen nanofiber fragments, acting as the structural reinforcement component, increased the overall storage modulus of the NHC to a level comparable to native soft tissues while maintaining a sufficiently high degree of porosity of the hydrogel phase to allow host cell infiltration following subcutaneous injection of the NHC microparticles. More importantly, the NHC promoted macrophage/monocyte infiltration, migration, and spreading, sustained cell recruitment over time, and enhanced the proangiogenic effect and recruitment of PDGFR alpha+ perivascular progenitor cells, leading to extensive adipose tissue remodeling. This study demonstrates the regenerative potential of the injectable NHC microgels as an off-the-shelf solution for devastating soft tissue losses.

Promoting regeneration after segmental nerve injury repair is a challenge, but improving angiogenesis could be beneficial. Macrophages facilitate regeneration after injury by promoting angiogenesis. Our aim in this study was to evaluate the feasibility and effects of transplanting exogenous macrophages to a segmental nerve injury.

Scavenging free radicals and reducing inflammatory reaction to relieve the secondary damage are important issues in the spinal cord injury (SCI) therapeutic strategy. Nanozymes attract more attention in the drug development of SCI due to the high stability, long-lasting catalytic capacity, and multienzyme-like properties. Herein, we constructed a Rapamycin (Rapa)-loaded and hollow mesoporous Prussian blue (HMPB)-based nanozyme (RHPAzyme) to realize the combined antioxidation and anti-inflammation combination therapy of SCI. Furthermore, activated cell penetrating peptide (ACPP) is modified onto nanozyme to endow the effectively ability of lesion area-targeting. This RHPAzyme exhibits ROS scavenging capacity with the transformation of Fe2+/Fe3+ valance and cyanide group of HMPB to achieve multienzyme-like activity. As expected, RHPAzyme scavenges the ROS overproduction and reduces inflammation in oxygen-glucose deprivation (OGD)-induced damage via inhibiting MAPK/AKT signaling pathway. Furtherly, RHPAzyme exhibits the combined antioxidant and anti-inflammatory activity in vivo, which can effectively alleviate neuronal damage and promote motor function recovery in SCI mice. Overall, this study demonstrates the RHPAzyme induces an effective treatment of SCI by inhibiting oxygen-mediated cell apoptosis and suppressing inflammation-induced injury, thus reduces the nervous impairment and promotes motor function recovery.

Surgical technique and technology frequently coevolve. The brief history of blood vessel anastomosis is full of famous names. While the techniques pioneered by these surgeons have been well described, the technology that facilitated their advancements and their inventors deserve recognition. The mass production of laboratory microscopes in the mid-1800s allowed for an explosion of interest in tissue histology. This improved understanding of vascular physiology and thrombosis laid the groundwork for Carrel and Guthrie to report some of the first successful vascular anastomoses. In 1916, McLean discovered heparin. Twenty-four years later, Gordon Murray found that it could prevent thrombosis when performing end-to-end anastomosis. These discoveries paved the way for the first-in-human kidney transplantations. Otolaryngologists Nylen and Holmgren were the first to bring the laboratory microscope into the operating room, but Jacobson was the first to apply these techniques to microvascular anastomosis. His first successful attempt in 1960 and the subsequent development of microsurgical tools allowed for an explosion of interest in microsurgery, and several decades of innovation followed. Today, new advancements promise to make microvascular and vascular surgery faster, cheaper, and safer for patients. The future of surgery will always be inextricably tied to the creativity and vision of its innovators.

A bone marrow-derived mesenchymal stromal cell (MSC) transplant and a bioengineered nanofiber-hydrogel composite (NHC) have been shown to stimulate nervous tissue repair in the contused spinal cord in rodent models. Here, these two modalities were combined to assess their repair effects in the contused spinal cord in adult rats. Cohorts of contused rats were treated with MSC in NHC (MSC-NHC), MSC in phosphate-buffered saline (MSC-PBS), NHC, or PBS injected into the contusion site at 3 days post-injury. One week after injury, there were significantly fewer CD68+ cells in the contusion with MSC-NHC and NHC, but not MSC-PBS. The reduction in CD86+ cells in the injury site with MSC-NHC was mainly attributed to NHC. One and eight weeks after injury, we found a greater CD206+/CD86+ cell ratio with MSC-NHC or NHC, but not MSC-PBS, indicating a shift from a pro-inflammatory towards an anti-inflammatory milieu in the injury site. Eight weeks after injury, the injury size was significantly reduced with MSC-NHC, NHC, and MSC-PBS. At this time, astrocyte, and axon presence in the injury site was greater with MSC-NHC compared with MSC-PBS. We did not find a significant effect of NHC on MSC transplant survival, and hind limb function was similar across all groups. However, we did find fewer macrophages at 1 week post-injury, more macrophages polarized towards a pro-regenerative phenotype at 1 and 8 weeks after injury, and reduced injury volume, more astrocytes, and more axons at 8 weeks after injury in rats with MSC-NHC and NHC alone compared with MSC-PBS; these findings were especially significant between rats with MSC-NHC and MSC-PBS. The data support further study in the use of an NHC-MSC combination transplant in the contused spinal cord.

Neuroinflammation is critically involved in the repair of spinal cord injury (SCI), and macrophages associated with inflammation propel the degeneration or recovery in the pathological process. Currently, efforts have been focused on obtaining efficient therapeutic anti-inflammatory drugs to treat SCI. However, these drugs are still unable to penetrate the blood spinal cord barrier and lack the ability to target lesion areas, resulting in unsatisfactory clinical efficacy. Herein, a polymer-based nanodrug delivery system is constructed to enhance the targeting ability. Because of increased expression of matrix metalloproteinases (MMPs) in injured site after SCI, MMP-responsive molecule, activated cell-penetrating peptides (ACPP), is introduced into the biocompatible polymer PLGA-PEI-mPEG (PPP) to endow the nanoparticles with the ability for diseased tissue-targeting. Meanwhile, etanercept (ET), a clinical anti-inflammation treatment medicine, is loaded on the polymer to regulate the polarization of macrophages, and promote locomotor recovery. The results show that PPP-ACPP nanoparticles possess satisfactory lesion targeting effects. Through inhibited consequential production of proinflammation cytokines and promoted anti-inflammation cytokines, ET@PPP-ACPP could decrease the percentage of M1 macrophages and increase M2 macrophages. As expected, ET@PPP-ACPP accumulates in lesion area and achieves effective treatment of SCI; this confirmed the potential of nano-drug loading systems in SCI immunotherapy.

Due to their intrinsic injectable and self-healing characteristics, dynamic hydrogels, based on dynamic covalent bonds, have gained a great attention. In this study, a novel dynamic hydrogel based on the boronic ester dynamic covalent bond is facilely developed using phenylboronic acid-modified hyaluronic acid (HA-PBA) and plant-derived polyphenol-tannic acid (TA). The dynamic hydrogel gelated quickly under mild conditions and had favorable viscoelastic properties with good self-healing and shear-thinning capabilities. Moreover, the simultaneous utilization of TA as a reductant for the green synthesis of silver nanoparticles (AgNP) inspired the preparation of a TA-reduced AgNP hybrid dynamic hydrogel with potent and broad-spectrum antibacterial activities. The dynamic hydrogels could also be applied for pH- and reactive oxygen species (ROS)-responsive release of loaded protein molecules without showing evident cytotoxicity and hemolysis in vitro. In addition, the dynamic hydrogels showed the anti-oxidative properties of high free radical and ROS scavenging capacity, which was verified by the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical assay and ROS fluorescence staining. Overall, this novel class of cytocompatible, self-healing, dual stimuli responsive, antibacterial, anti-oxidative, and injectable hydrogels could be promising as a wound dressing for chronic wound healing.