Regenerative Biomaterials最新文献

The most significant challenge facing magnesium alloy stents is their ability to withstand complex deformation during their application. To gain a deeper understanding of the impact of stent deformation on the protective capabilities of the coating, this paper presents an amplified stent deformation model. The models were coated with either a low elongation material-Poly(D, L-lactide) (PDLLA) or a high elongation material-Poly(butylene adipate-co-terephthalate) (PBAT), followed by the application of a rapamycin-loaded PLGA as drug-eluting layer. Coating integrity and thickness were examined via scanning electron microscopy (SEM), while electrochemical impedance spectroscopy and long-term immersion tests assessed corrosion behavior on the deformation model. Finite element analysis using Comsol simulated the stress-strain distribution during compression and tension, and cellular automata (CA) models were employed to simulate the corrosion process. The drug release tests were conducted in vitro, and in vivo performance was evaluated through stent implantation in rabbit carotid arteries using optical coherence tomography, SEM, and histological analysis. Results demonstrated that PBAT coatings maintained structural integrity without apparent microcracks after deformation, whereas PDLLA coatings exhibited significant cracking and significantly reduced charge transfer resistance. This reduction in protective performance is observed to occur predominantly in regions of strain concentration with more porosity during the deformation process. CA simulations and immersion tests confirmed slower degradation rates under PBAT. Moreover, PBAT-coated stents achieved larger luminal areas, reduced neointimal formation, and lower restenosis rates compared to PDLLA-coated counterparts in vivo. In conclusion, PBAT coatings offer robust protection against deformation-induced damage and corrosion, representing a promising strategy for enhancing the long-term performance of Mg alloy stents.

Conventional hemodialysis and hemodiafiltration prove less effective at removing protein-bound uremic toxins (PBUTs) from the bloodstream of end-stage renal disease patients, primarily because PBUTs cannot pass through the small pores in the polymeric membranes. Hemoperfusion is an extracorporeal blood purification technique that employs an adsorption mechanism to remove multiple uremic toxins from such patients. Yet, the efficacy of hemoperfusion is constrained by some limitations of contemporary adsorbents, such as suboptimal capacity to adsorb PBUTs and poor hemocompatibility, presenting significant barriers for their clinical application. To address these challenges, we engineered a tailored hemoperfusion adsorbent by compounding sulfonated polysulfone (SPSf) and polyethyleneimine (PEI) into polyethersulfone (PES) microspheres to effectively capture and remove PBUTs through electrostatic interactions. Specifically, we introduced sulfuric acid into the coagulation bath to increase the adsorption amount of the developed adsorbent (H-PES/SPSf@PEI microspheres), to neutralize strong positive charge of PEI and to improve hemocompatibility. The tailored H-PES/SPSf@PEI microspheres neither damage blood cells nor activate the complement pathway when they contact with human blood. Moreover, H-PES/SPSf@PEI microspheres have a high adsorption amount toward major PBUTs, including hippuric acid (HA, 34.24 mg/g), 3-indoleacetic acid (IAA, 49.19 mg/g), p-cresol sulfate (PCS, 40.31 mg/g) and indoxyl sulfate (IS, 128.67 mg/g) by fitting adsorption isotherms. In a simulated hemoperfusion setting, the removal ratio of IS, IAA, PCS and HA by H-PES/SPSf@PEI microspheres reaches nearly 75.33%, 41.73%, 44.36% and 21.11%, respectively, with 47.89% of IS, 40.64% of IAA, 44.42% of PCS and 37.35% of HA being removed from BSA solution. In conclusion, H-PES/SPSf@PEI microspheres hold a potential to eliminate PBUTs from patients with end-stage renal disease.

Angiogenesis plays a pivotal role in the wound healing process by supplying essential nutrients and oxygen to regenerating tissues thereby supporting tissue remodeling. Promoting the formation of new blood vessels is, therefore, a critical therapeutic strategy, particularly for ischemic and chronic wounds, where impaired blood supply often leads to delayed or incomplete healing. However, the development of effective pro-angiogenic biomaterials remains a challenge. In this work, by incorporating natural spider silk proteins (SSP) with poly(L-lactic acid) (PLLA) nanofiber via electrospinning, we developed a pro-angiogenic wound dressing. The incorporation of SSP led to a reduction in fiber diameter and the formation of a hierarchical structure that mimics the native extracellular matrix. Moreover, the combined effects of these biophysical and SSP-derived biochemical cues synergistically enhanced vascular regeneration, resulting in significant improvements in three key angiogenic parameters compared to pure PLLA controls: a 16.3% increase in blood vessel count, a 118.6% increase in vascular branching and a 32.8% increase in total vessel length. In vivo wound healing experiments showed a 29% improvement in the wound healing rate compared to the control group. This dual-mechanism strategy, synergizing structural biomimicry with bioactive cues, establishes a multifunctional platform to address complex wound healing challenges, particularly in ischemic and chronic wounds.

Intraocular lens (IOL) is a crucial implant for cataract therapy. Posterior capsule opacification (PCO) is the most common postoperative complication after IOL implantation, which is the abnormal hyperplasia of the residual lens epithelial cells (LECs) after IOL implantation in cataract surgery. It is reported that the cellular microenvironment in the lens capsule changes after surgery, such as the elevated secretion of matrix metalloproteinases (MMPs) and a decrease in pH due to undesired cell proliferation. In this study, MMP-2 and pH-triggered drug delivery polysaccharide multilayer coating was designed and introduced onto the IOL surface for obtaining the cellular microenvironment-sensitive drug-eluting intraocular implant. The methacrylated heparin (HEP-MA) was synthesized and used to layer-by-layer self-assemble with the doxorubicin-loaded chitosan nanoparticles on the IOL surface. The matrix metalloproteinase-2 (MMP-2) sensitive peptide with cysteine contained in both ends (GCRD-GPQGIWGQ-DRCG) was then used to crosslink the polysaccharide multilayer via the Michael addition reaction between sulfhydryl group in cysteines and double bonds in methacrylate groups. The multilayer construction and subsequent cross-linking were validated through ultraviolet-visible spectrophotometer (UV-Vis) and Fourier transform infrared spectroscopy (FTIR). After modification, the IOL material surface becomes more hydrophilic while the optical properties were well maintained. The MMP-2 and pH-sensitive drug sustained-release coating were successfully obtained on the IOL surface via such design. The enzyme-triggered cell proliferation inhibition was realized in the in vitro experiments. In an animal model, significant up-regulation of MMP-2 was observed in the aqueous humor after cataract surgery. The multi-functionalized polysaccharide-coated IOL implanted in the animal eye via cataract surgery effectively inhibits PCO formation while it keeps good in vivo biosafety.

Skin aging, characterized by reduced collagen regeneration, chronic inflammation and heightened skin cancer risk, poses a significant challenge. Collagen-based materials, employed as dermal fillers to smooth wrinkles, have attained extensive utilization. Nevertheless, traditional animal-derived collagen protein primarily presents concerns pertaining to disease risks, potential immunological reactions, and batch instability. Here, we introduced a highly durable 1,4-butanediol diglycidyl ether cross-linked recombinant human collagen type III (rhCol III) microgel as dermal filler for rejuvenating aging skin. The rhCol III microgel exhibited exceptional thermostability, mechanical strength and injectability. Subsequently, we established a UV-photoaging skin animal model and chose rhCol III microgel as a bioactive material for in vivo implantation, systematically comparing its biological effect with commercialized collagen I (Col I) derived from porcine skin (pCollagen) and hyaluronic acid through histological observation, immunofluorescence staining, hydroxyproline quantification and analysis of specific gene expression. Outcomes indicated rhCol III microgel prompted augmented production of Col I, collagen III (Col III) and elastic fibers, thereby contributing to the remodeling of the extracellular matrix (ECM). In summary, our investigation contributed to robust biosafety and rejuvenation of UV-induced skin photoaging by rhCol III under a single injection for 6 weeks. Despite the imperative ongoing efforts required for the successful translation from bench to clinic, the discernibly superior safety and efficacy of rhCol III microgel present an innovative methodology in combating skin aging, offering significant promise in medical cosmetology and tissue engineering.

Bone defects affect millions of people annually, making bone tissue of particular interest for developing treatments. Current strategies for healing suffer drawbacks. Regenerative engineering seeks to achieve efficient bone regeneration by utilizing synthetic bone grafts to evade these drawbacks. One material that offers such benefits is a class of functional graphenic material, known as Phosphate Graphenes. While many of our studies have focused on Calcium Phosphate Graphene, magnesium is also osteogenic. Therefore, in this study, we utilized regenerative engineering techniques to incorporate Magnesium Phosphate Graphene (MgPG) into poly(lactic-co-glycolic acid) (PLGA) to fabricate composite microsphere-based matrices as a potential synthetic bone graft. Employing different amounts of MgPG within PLGA matrices, we studied the effect of MgPG on the morphological, structural, physical and biological characteristics. MgPG-containing matrices demonstrated great mechanical strength, hydrophilicity and degradability without compromising matrix morphology. Because MgPG is a graphene oxide derivative with magnesium and phosphate ions capable of supporting bone healing as inducerons, we next evaluated the cytocompatibility and osteogenic potential of these PLGA/MgPG composite matrices. MgPG matrices demonstrated high cell viability and proliferation of MC3T3-E1 cells as well as increased osteogenic activity reported by alkaline phosphatase activity, calcium deposition and gene expression of Col1a1, osteocalcin, bone sialoprotein and Sp7. Lastly, we investigated the gene expression profile of markers/targets of the canonical β-catenin dependent Wnt signaling pathway with and without inhibitor DKK1 to understand the potential underlying mechanism behind the enhanced osteogenic potential of MgPG. In response to MgPG, gene expression of β-catenin increased, while protein expression of BMP-2 and WISP-1 also increased. These results suggest the influence of MgPG on the Wnt pathway in relation to osteogenic differentiation. With further study, MgPG matrices may provide practical solutions to the problem of effectively regenerating critical-sized bone defects, which remains a challenge in orthopaedics.

The versatile multi-territory perforator flap remains a cornerstone of reconstructive surgery for diabetic ulcerations, yet its clinical efficacy faces significant challenges in hyperglycemic conditions. The diabetic milieu significantly exacerbates tissue ischemia through augmented chronic inflammation and impaired angiogenesis, which collectively harm flap perfusion and compromise its overall viability. A major postoperative complication is distal flap necrosis, which is closely associated with the critical "Choke zone," a hypoperfused transitional area that exhibits delayed vascular recruitment and suboptimal angiogenesis. This vascular bottleneck creates a precarious balance between tissue oxygen demand and supply, ultimately compromising flap viability. To address this issue, we have developed the engineering stem cell exosomes by encapsulating metformin-loaded Mesoporous silica nanoparticles into BMSC exosomes (M-MS@EXO NPs), enabling the release of metformin. Compared to traditional oral medication, delivering metformin through engineered exosomes allows for precise administration in diabetic wounds. The multifunctional M-MS@EXO NPs exhibit dual pharmacological activity by reducing the secretion of inflammatory cytokines while effectively remodeling the vascular niche within the diabetic microenvironment. Additionally, the M-MS@EXO NPs show anti-inflammatory and angiogenesis effects by inhibiting TNF/apoptosis and enhancing VEGF signaling pathways in vitro. In the dorsal multi-territory perforator flap model of type 2 diabetes, the M-MS@EXO NPs demonstrate the ability to alleviate inflammation and promote neovascularization of the Choke zone, reducing distal necrosis, which holds great promise for improving flap survival in diabetes.

Bioresorbable stents (BRS) have emerged as a groundbreaking development in the field of percutaneous coronary intervention (PCI) as they address the long-standing concerns of metallic stents. Nevertheless, the observed higher thrombosis rates in the first generation BRS, i.e. ABSORB^®, might be attributed to their thicker struts, slower degradation rate and structural dismantling of partially endothelialized stents. In this study, measures have been taken to overcome these limitations include reducing strut thickness, modifying the structural design to maintain radial strength with thinner round cross section struts and using a new material poly(L-lactide-co-ɛ-caprolactone) (PLCL 95/5) that is tougher and degrade faster than poly(L-lactic acid) (PLLA).Given the excellent biocompatibility of PLCL materials, the US FDA has approved their use in clinical applications. PLCL stents can be used to treat diseases such as tracheal stenosis and tracheoesophageal fistula, and can also be applied in the construction of other tissue engineering stents, such as nerve conduitsand fat filling stents. The newly designed coronary stents were fabricated using a 3D printing technology with a rotating platform, coated with a paclitaxel coating and comprehensive in vitro research was conducted. It was the first to undergo tests in animals. Results showed the novel paclitaxel eluting PLCL stents had super-flexible structure, thinner round cross-sectional struts, a faster degradation profile and satisfactory hemocompatibility. With a paclitaxel dose of 0.57 μg/mm², the drug eluting stents showed very low degree of stenosis within 6 months of implantation in a porcine model. Overall, the results showed that the novel 3D printed PLCL drug eluting stent is a very promising candidate for next generation bioresorbable coronary stent.

Abnormal melanin production can lead to various pigmentary disorders, which significantly affect patients' quality of life and overall health. However, current clinical melanogenesis inhibitors have adverse side effects such as skin dryness, itching, erythema, etc. In this study, we used naturally isolated exosomes derived from Pinctada martensii mucus (PMMEXOs) and investigated the effects on melanin synthesis based on B16-F10 melanoma cells and zebrafish. We demonstrated that PMMEXOs effectively inhibited melanin production while exhibiting excellent biocompatibility. To elucidate the underlying mechanisms, RNA sequencing and bioinformatics analysis were employed, identifying 556 differentially expressed genes associated with PMMEXOs treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the involvement of the NF-κB signaling pathway in the regulation of melanogenesis. Further mechanistic studies confirmed that PMMEXOs significantly reduced tyrosinase activity and melanin content, accompanied by the downregulation of critical melanogenesis-related genes and proteins, including MITF, TYR, TYRP-1 and TRP-2. Notably, the anti-melanogenic effects of PMMEXOs were mediated by activation of the NF-κB signaling pathway, underscoring their regulatory role in melanin biosynthesis. Additionally, microRNA (miRNA) sequencing of PMMEXOs identified specific miRNAs implicated in immune regulation and modulation of the NF-κB pathway, further supporting their mechanistic involvement in melanin inhibition. These findings collectively position PMMEXOs as a promising and innovative therapeutic strategy for the prevention and treatment of pigmentary disorders such as melasma, age spots and wrinkles.

Bone serves as a critical structural framework, enabling movement and protecting internal organs. Consequently, maintaining skeletal health is a pivotal objective in bone tissue engineering. Bioactive metal ions, such as magnesium, strontium, zinc and copper, play essential roles in bone metabolism by participating in key physiological processes that sustain bone health and support regeneration. Recent studies indicate that these ions enhance the physicochemical properties and biological performance of bone tissue engineering materials, thereby facilitating osseointegration through diverse mechanisms. Specifically, magnesium promotes osteogenic differentiation; strontium inhibits osteoclast activity; zinc exhibits antibacterial properties; and copper facilitates vascularization for osteogenesis. Therefore, incorporating bioactive metal ions has emerged as a prevalent strategy in bone tissue engineering to address orthopedic disorders. This review systematically summarizes the roles of magnesium, strontium, zinc and copper in bone repair and regeneration. It provides an in-depth analysis of engineered materials incorporating these ions, with a focus on their applications and modifications across various material types. Furthermore, we explore the synergistic effects of combining these metal ions in bone tissue engineering, emphasizing their enhanced biological properties. By synthesizing recent research findings, this review aims to provide new insights and potential breakthroughs in leveraging bioactive metal ions for advancing treatments of orthopedic diseases.