ROS-responsive drug-releasing injectable microgels for ameliorating myocardial infarction.

Despite of the recent advances in regulatory T cell (Treg) therapy, a limited number of available cells and specificity at the desired tissue site have severely compromised their efficacy. Herein, an injectable drug-releasing (MTK-TK-drug) microgel system in response to in situ stimulation by reactive oxygen species (ROS) was constructed with a coaxial capillary microfluidic system and UV curing. The spherical microgels with a size of 150 µm were obtained. The MTK-TK-drug microgels efficiently converted the pro-inflammatory Th17 cells into anti-inflammatory regulatory T cells (Treg) cells in vitro, and the ROS-scavenging materials synergistically enhanced the effect by modulating the inflammation microenvironment. Thus, the microgels significantly reduced cardiomyocyte apoptosis and decreased the inflammatory response in the early stages of post-myocardial infarction (MI) in vivo, thereby reducing fibrosis, promoting vascularization, and preserving cardiac function. Overall, our results indicate that the MTK-TK-drug microgels can attenuate the inflammatory response and improve MI therapeutic effects in vivo.

Shape-recovery of implanted shape-memory devices remotely triggered via image-guided ultrasound heating.

Shape-memory materials hold great potential to impart medical devices with functionalities useful during implantation, locomotion, drug delivery, and removal. However, their clinical translation is limited by a lack of non-invasive and precise methods to trigger and control the shape recovery, especially for devices implanted in deep tissues. In this study, the application of image-guided high-intensity focused ultrasound (HIFU) heating is tested. Magnetic resonance-guided HIFU triggered shape-recovery of a device made of polyurethane urea while monitoring its temperature by magnetic resonance thermometry. Deformation of the polyurethane urea in a live canine bladder (5 cm deep) is achieved with 8 seconds of ultrasound-guided HIFU with millimeter resolution energy focus. Tissue sections show no hyperthermic tissue injury. A conceptual application in ureteral stent shape-recovery reduces removal resistance. In conclusion, image-guided HIFU demonstrates deep energy penetration, safety and speed.

An antibacterial and anti-oxidant hydrogel containing hyperbranched poly-l-lysine and tea polyphenols accelerates healing of infected wound.

Both bacteria-infection and excessive inflammation delay the wound healing process and even create non-healing wound, thus it is highly desirable to endow the wound dressing with bactericidal and anti-oxidation properties. Herein an antibacterial and antioxidation hydrogel based on Carbomer 940 (CBM) and hydroxypropyl methyl cellulose (HPMC) loaded with tea polyphenols (TP) and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The hydrogel killed 99.9 % of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) at 107 CFU mL-1, and showed strong antioxidation against H2O2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH) radicals without noticeable cytotoxicity in vitro. The CBM/HPMC/HBPL/TP hydrogel significantly shortened the inflammatory period of the MRSA-infected full-thickness skin wound of rats in vivo, with 2 orders of lower MRSA colonies compared with the blank control, and promoted the wound closure especially at the earlier stage. The inflammation was suppressed and the vascularization was promoted significantly as well, resulting in reduced pro-inflammatory factors including interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and increased anti-inflammatory factors such as interleukin-4 (IL-4) and interleukin-10 (IL-10).

A tough, antibacterial and antioxidant hydrogel dressing accelerates wound healing and suppresses hypertrophic scar formation in infected wounds.

Wound management is an important issue that places enormous pressure on the physical and mental health of patients, especially in cases of infection, where the increased inflammatory response could lead to severe hypertrophic scars (HSs). In this study, a hydrogel dressing was developed by combining the high strength and toughness, swelling resistance, antibacterial and antioxidant capabilities. The hydrogel matrix was composed of a double network of polyvinyl alcohol (PVA) and agarose with excellent mechanical properties. Hyperbranched polylysine (HBPL), a highly effective antibacterial cationic polymer, and tannic acid (TA), a strong antioxidant molecule, were added to the hydrogel as functional components. Examination of antibacterial and antioxidant properties of the hydrogel confirmed the full play of the efficacy of HBPL and TA. In the in vivo studies of methicillin-resistant Staphylococcus aureus (MRSA) infection, the hydrogel had shown obvious promotion of wound healing, and more profoundly, significant suppression of scar formation. Due to the common raw materials and simple preparation methods, this hydrogel can be mass produced and used for accelerating wound healing while preventing HSs in infected wounds.

A Sequential Dual Functional Supramolecular Hydrogel with Promoted Drug Release to Scavenge ROS and Stabilize HIF-1α for Myocardial Infarction Treatment.

Myocardial infarction (MI) has a characteristic inflammatory microenvironment due to the overproduction of reactive oxygen species (ROS) and causes the extraordinary deposition of collagen and thereby fibrosis. An on-demand adaptive drug releasing hydrogel is designed to modulate the inflammatory microenvironment and inhibit cardiac fibroblasts (CFs) proliferation post MI by scavenging the overproduced ROS and releasing 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (DPCA) to maintain the expression of hypoxia-inducible factor 1α (HIF-1α). DPCA is prefabricated to a prodrug linked with disulfide bond (DPCA-S-S-OH). The DPCA-S-S-OH and carboxylated calixarene (CSAC4A) are grafted onto the backbone of methacrylated hyaluronic acid (HAMA) to obtain HAMA-S-S-DPCA and HAMA-CA, respectively, which are further reacted to form a dual network hydrogel (R+ /DPCA(CA)) with covalent linking and host-guest interaction between DPCA and CSAC4A. The ROS-triggered hydrolysis of ester bond and subsequently sustaining release of DPCA from the cavity of CSAC4A jointly cause the constant expression of HIF-1α, which significantly restricts the CFs proliferation, leading to suppressed fibrosis and promoted heart repair.

Hypoxia and Matrix Metalloproteinase 13-Responsive Hydrogel Microspheres Alleviate Osteoarthritis Progression In Vivo.

The occurrence of osteoarthritis (OA) is highly associated with the inflammatory hypoxic microenvironment. Yet currently no attention has been paid to fabricating hypoxia-responsive platforms for OA treatment. Herein, an injectable hydrogel microsphere system (HAM-SA@HCQ) focusing on the hypoxic inflamed joint is prepared with methacrylate-modified sulfonated azocalix[4]arene (SAC4A-MA), methacrylated hyaluronic acid (HA-MA), and dithiol-terminated matrix metalloproteinase 13 (MMP-13) sensitive peptide via a microfluidic device and photo crosslinking technique, followed by encapsulation of the anti-inflammatory drug hydroxychloroquine (HCQ) through host-guest interaction. Owing to the hydrophobic deep cavity, phenolic units, and azo bonds of SAC4A-MA, the hydrogel microspheres show strong drug loading capacity, prominent reactive oxygen species (ROS) scavenging capability, and specific hypoxia-responsive drug release ability. In the OA tissue microenvironment, the hydrogel microspheres undergo degradation by excessive MMP-13 and release HCQ under the hypoxia condition, which synergizes with the ROS-scavenging calixarene to inhibit the inflammatory response of macrophages. After being injected into the OA-inflamed joint, the HAM-SA@HCQ can significantly attenuate the oxidative stress, downregulate the expression of hypoxia-induced factor-1α and inflammatory cytokines, and prevent the cartilage from being destroyed.

Co-delivery of azithromycin and ibuprofen by ROS-responsive polymer nanoparticles synergistically attenuates the acute lung injury.

Bacterial infection causes lung inflammation and recruitment of several inflammatory factors that may result in acute lung injury (ALI). During bacterial infection, reactive oxygen species (ROS) and other signaling pathways are activated, which intensify inflammation and increase ALI-related mortality and morbidity. To improve the ALI therapy outcome, it is imperative clinically to manage bacterial infection and excessive inflammation simultaneously. Herein, a synergistic nanoplatform (AZI+IBF@NPs) constituted of ROS-responsive polymers (PFTU), and antibiotic (azithromycin, AZI) and anti-inflammatory drug (ibuprofen, IBF) was developed to enable an antioxidative effect, eliminate bacteria, and modulate the inflammatory milieu in ALI. The ROS-responsive NPs (PFTU NPs) loaded with dual-drugs (AZI and IBF) scavenged excessive ROS efficiently both in vitro and in vivo. The AZI+IBF@NPs eradicated Pseudomonas aeruginosa (PA) bacterial strain successfully. To imitate the entry of bacterial-derived compounds in body, a lipopolysaccharide (LPS) model was adopted. The administration of AZI+IBF@NPs via the tail veins dramatically reduced the number of neutrophils, significantly reduced cell apoptosis and total protein concentration in vivo. Furthermore, nucleotide oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3) and Interleukin-1 beta (IL-1ß) expressions were most effectively inhibited by the AZI+IBF@NPs. These findings present a novel nanoplatform for the effective treatment of ALI.

In vivo self-assembled shape-memory polyurethane for minimally invasive delivery and therapy.

Advanced elastomers are highly in demand for the fabrication of medical devices for minimally invasive surgery (MIS). Herein, a shape memory and self-healing polyurethane (PCLUSe) composed of semi-crystalline poly(ε-caprolactone) (PCL) segments and interchangeable and antioxidative diselenide bonds was designed and synthesized. The excellent shape memory of PCLUSe contributed to the smooth MIS operation, leading to less surgical wounds than in the case of sternotomy. The diselenide bonds of PCLUSe contributed to the rapid self-healing under 405 nm irradiation within 60 s, and the alleviation of tissue oxidation post injury. After being delivered through a 10 mm diameter trocar onto a beating canine heart by MIS, two shape-recovered PCLUSe films self-assembled (self-healing) into a larger single patch (20 × 10 × 0.2 mm3) under the trigger of laser irradiation in situ, which could efficiently overcome the limited-size problem within MIS and meet a larger treatment area. The diselenide bonds in the PCLUSe cardiac patches protected the myocardium under oxidative stress post myocardial infarction (MI), and significantly maintained the cardiac functions.

Simplified α2-macroglobulin as a TNF-α inhibitor for inflammation alleviation in osteoarthritis and myocardial infarction therapy.

Tumor necrosis factor α (TNF-α) is a leading proinflammatory cytokine as the master regulator of inflammation in chronic inflammation diseases. Although TNF-α antagonists such as small molecules and peptides are in development, comparable effectiveness in TNF-α neutralization is hardly achieved only with TNF-α capture. In this study, simplified α2-macroglobulin (SM) as a novel TNF-α inhibitor was fabricated to relieve inflammation response by TNF-α capture and internalization with lysosomal degradation. SM was prepared by conjugating a TNF-α-targeting peptide with a receptor binding domain (RBD) derived from α2-macroglobulin through a synthetic biology strategy. SM exhibited effective capture and bioactivity inhibition of TNF-α. Improved endocytosis of TNF-α into lysosomes was observed with SM in macrophages. Even challenged with LPS/IFNγ, the macrophages showed relieved inflammation response with SM treatment. When administrated in chronic inflammation injury in vivo, SM achieved comparable therapeutic efficacy with Infliximab, showing ameliorated cartilage degeneration with relieved inflammation in osteoarthritis (OA) and preserved cardiac function with mitigated myocardium injury in myocardial infarction (MI). These results suggest that SM functioning in TNF-α capture-internalization mechanism might be promising therapeutic alternatives of TNF-α antibodies.

A biodegradable, flexible photonic patch for in vivo phototherapy.

Diagnostic and therapeutic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, we present a flexible, biodegradable photonic device called iCarP with a micrometer scale air gap between a refractive polyester patch and the embedded removable tapered optical fiber. ICarP combines the advantages of light diffraction by the tapered optical fiber, dual refractions in the air gap, and reflection inside the patch to obtain a bulb-like illumination, guiding light towards target tissue. We show that iCarP achieves large area, high intensity, wide spectrum, continuous or pulsatile, deeply penetrating illumination without puncturing the target tissues and demonstrate that it supports phototherapies with different photosensitizers. We find that the photonic device is compatible with thoracoscopy-based minimally invasive implantation onto beating hearts. These initial results show that iCarP could be a safe, precise and widely applicable device suitable for internal organs and tissue illumination and associated diagnosis and therapy.

A triphasic biomimetic BMSC-loaded scaffold for osteochondral integrated regeneration in rabbits and pigs.

Osteochondral tissue involves cartilage, calcified cartilage and subchondral bone. These tissues differ significantly in chemical compositions, structures, mechanical properties and cellular compositions. Therefore, the repairing materials face different osteochondral tissue regeneration needs and rates. In this study, we fabricated an osteochondral tissue-inspired triphasic material, which was composed of a poly(lactide-co-glycolide) (PLGA) scaffold loaded with fibrin hydrogel, bone marrow stromal cells (BMSCs) and transforming growth factor-ß1 (TGF-ß1) for cartilage tissue, a bilayer poly(L-lactide-co-caprolactone) (PLCL)-fibrous membrane loaded with chondroitin sulfate and bioactive glass, respectively, for calcified cartilage, and a 3D-printed calcium silicate ceramic scaffold for subchondral bone. The triphasic scaffold was press-fitted into the osteochondral defects in rabbit (cylindrical defects with a diameter of 4 mm and a depth of 4 mm) and minipig knee joints (cylindrical defects with a diameter of 10 mm and a depth of 6 mm). The µ-CT and histological analysis showed that the triphasic scaffold was partly degraded, and significantly promoted the regeneration of hyaline cartilage after they were implanted in vivo. The superficial cartilage showed good recovery and uniformity. The calcified cartilage layer (CCL) fibrous membrane was in favor of a better cartilage regeneration morphology, a continuous cartilage structure and less fibrocartilage tissue formation. The bone tissue grew into the material, while the CCL membrane limited bone overgrowth. The newly generated osteochondral tissues were well integrated with the surrounding tissues too.

Recent Advances in Biomaterials-Based Therapies for Alleviation and Regeneration of Traumatic Brain Injury.

Traumatic brain injury (TBI), a major public health problem accompanied with numerous complications, usually leads to serve disability and huge financial burden. The adverse and unfavorable pathological environment triggers a series of secondary injuries, resulting in serious loss of nerve function and huge obstacle of endogenous nerve regeneration. With the advances in adaptive tissue regeneration biomaterials, regulation of detrimental microenvironment to reduce the secondary injury and to promote the neurogenesis becomes possible. The adaptive biomaterials could respond and regulate biochemical, cellular, and physiological events in the secondary injury, including excitotoxicity, oxidative stress, and neuroinflammation, to rebuild circumstances suitable for regeneration. In this review, the development of pathology after TBI is discussed, followed by the introduction of adaptive biomaterials based on various pathological characteristics. The adaptive biomaterials carried with neurotrophic factors and stem cells for TBI treatment are then summarized. Finally, the current drawbacks and future perspective of biomaterials for TBI treatment are suggested.

An electrospun scaffold functionalized with a ROS-scavenging hydrogel stimulates ocular wound healing.

Ocular alkali burn is a serious ophthalmic emergency. Highly penetrative alkalis cause strong inflammatory responses leading to persistent epithelial defects, acute corneal perforation and severe scarring, and thereby persistent pain, loss of vision and cicatricial sequelae. Early and effective anti-inflammation management is vital in reducing the severity of injury. In this study, a double network biomaterial was prepared by compounding electrospinning nanofibres of thioketal-containing polyurethane (PUTK) with a reactive oxygen species (ROS)-scavenging hydrogel (RH) fabricated by crosslinking poly(poly(ethylene glycol) methyl ether methacrylate-co-glycidyl methacrylate) with thioketal diamine and 3,3'-dithiobis(propionohydrazide). The developed PUTK/RH patch exhibited good transparency, high tensile strength and increased hydrophilicity. Most importantly, it demonstrated strong antioxidant activity against H2O2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH). Next, a rat corneal alkali burn model was established, and the PUTK/RH patch was transplanted on the injured cornea. Reduced inflammatory cell infiltration was revealed by confocal microscopy, and lower expression levels of genes relative to inflammation, vascularization and scarring were identified by qRT-PCR and western blot. Fluorescein sodium dyeing, hematoxylin and eosin (H&E) staining and immunohistochemical staining confirmed that the PUTK/RH patch could accelerate corneal wound healing by inhibiting inflammation, promoting epithelial regeneration and decreasing scar formation. STATEMENT OF SIGNIFICANCE: Ocular alkali burn is a serious ophthalmic emergency, characterized with persistent inflammation and irreversible vision loss. Oxidative stress is the main pathological process at the acute inflammatory stage, during which combined use of glucocorticoids and amniotic membrane transplantation is the most widely accepted treatment. In this study, we fabricated a polyurethane electrospun nanofiber membrane functionalized with a ROS-scavenging hydrogel. This composite patch could be a promising amniotic membrane substitute, possessing with a transparent appearance, elasticity and anti-inflammation effect. It could be easily transplanted onto the alkali-burned corneas, resulting in a significant inhibition of stromal inflammation and accelerating the recovery of corneal transparency. The conception of ROS-scavenging wound patch may offer a new way for ocular alkali burn.

A reactive oxygen species-responsive hydrogel encapsulated with bone marrow derived stem cells promotes repair and regeneration of spinal cord injury.

Spinal cord injury (SCI) is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes, such as excessive reactive oxygen species (ROS) produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment, leading to the widespread apoptosis of the neuron cells, glial and oligodendroctyes. In this study, a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells (BMSCs), which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment. The hydrogel could effectively encapsulate BMSCs, and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS, attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), resulting in a reduced cell apoptosis in the spinal cord tissue. The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation, and improved the neurogenesis of the spinal cord tissue, and thus distinctly enhanced the motor functional recovery of SCI rats. Our work provides a combinational strategy against ROS-mediated oxidative stress, with potential applications not only in SCI, but also in other central nervous system diseases with similar pathological conditions.

Submicron-Sized In Situ Osmotic Pressure Sensors for In Vitro Applications in Biology.

Physical forces are important cues in determining the development and the normal function of biological tissues. While forces generated by molecular motors have been widely studied, forces resulting from osmotic gradients have been less considered in this context. A possible reason is the lack of direct in situ measurement methods that can be applied to cell and organ culture systems. Herein, novel kinds of resonance energy transfer (FRET)-based liposomal sensors are developed, so that their sensing range and sensitivity can be adjusted to satisfy physiological osmotic conditions. Several types of sensors are prepared, either based on polyethylene glycol- (PEG)ylated liposomes with steric stabilization and stealth property or on crosslinked liposomes capable of enduring relatively harsh environments for liposomes (e.g., in the presence of biosurfactants). The sensors are demonstrated to be effective in the measurement of osmotic pressures in pre-osteoblastic in vitro cell culture systems by means of FRET microscopy. This development paves the way toward the in situ sensing of osmotic pressures in biological culture systems.

A broad-spectrum antibacterial and tough hydrogel dressing accelerates healing of infected wound in vivo.

Infection can disturb the wound healing process and lead to poor skin regeneration, chronic wound, septicemia and even death. To combat the multi-drug resistance bacteria or fungi, it is urgent and necessary to develop advanced antimicrobial wound dressings. In this study, a composite hydrogel dressing composed of polyvinyl alcohol (PVA), agarose, glycerol and antibacterial hyperbranched polylysine (HBPL) was prepared by a freeze-thawing method. The hydrogel showed robust mechanical properties, and the HBPL in the hydrogel displayed effective and broad-spectrum antimicrobial properties to bacteria and fungi as well as biofilms. The composite hydrogel exhibited good biocompatibility with respect to the levels of cells, blood, tissue and main organs. In an animal experiment of an infected wound model, the hydrogel significantly eliminated the infection and accelerated the wound regeneration with better tissue morphology and angiogenesis. The hydrogel also successfully achieved scalable production of over 600 g with a yield over 90 %, suggesting the great potential for the application in practice.

Antifouling poly(PEGMA) grafting modified titanium surface reduces osseointegration through resisting adhesion of bone marrow mesenchymal stem cells.

As an alternative strategy to achieve the desired bone augmentation, tenting screw technology (TST) has considerably broadened the indications for implant treatment. Titanium tenting screws are typically used in TST to maintain the space for bone regeneration. However, a high degree of osteogenic integration complicate titanium tenting screw removal and impact the bone healing micro-environment. Previous efforts have been focused on modifying titanium surfaces to enhance osseointegration while ignoring the opposite process. Due to the vital role of bone marrow mesenchymal stem cells (BMSCs) in bone regeneration, it might be feasible to reduce osseointegration around titanium tenting screws by resisting the adhesion of BMSCs. Herein, poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was incorporated with a Ti surface in terms of surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The cell apoptosis analysis showed that the new surface would not induce the apoptosis of BMSCs. Then, the adhesive and proliferative behaviors of BMSCs on the surface were analyzed which indicated that the poly(PEGMA) surface could inhibit the proliferation of BMSCs through resisting the adhesion process. Furthermore, in vivo experiments revealed the presence of the poly(PEGMA) on the surface resulted in a lower bone formation and osseointegration compared with the Ti group. Collectively, this dense poly(PEGMA) surface of Ti may serve as a promising material for clinical applications in the future. STATEMENT OF SIGNIFICANCE: The poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was grafted onto a Ti surface by surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The PEGMA surface could reduce the osteogenic integration by preventing the adhesion of cells, resulting in a lower pullout force of the modified implant and thereby desirable and feasible applications in dental surgery.

A honeybee stinger-inspired self-interlocking microneedle patch and its application in myocardial infarction treatment.

Weak tissue adhesion remains a major challenge in clinical translation of microneedle patches. Mimicking the structural features of honeybee stingers, stiff polymeric microneedles with unidirectionally backward-facing barbs were fabricated and embedded into various elastomer films to produce self-interlocking microneedle patches. The spirality of the barbing pattern was adjusted to increase interlocking efficiency. In addition, the micro-bleeding caused by microneedle puncturing adhered the porous surface of the patch substrate to the target tissue via coagulation. In the demonstrative application of myocardial infarction treatment, the bioinspired microneedle patches firmly fixed on challenging beating hearts, significantly reduced cardiac wall stress and strain in the infarct, and maintained left ventricular function and morphology. In addition, the microneedle patch was minimally invasively implanted onto beating porcine heart in 10 minutes, free of sutures and adhesives. Therefore, the honeybee stinger-inspired microneedles could provide an adaptive and convenient means to implant patches for various medical applications. STATEMENT OF SIGNIFICANCE: Adhesion between tissue and microneedle patches with smooth microneedles is usually weak. We introduce a novel barbing method of fabricating unidirectionally backward facing barbs with controllable spirality on the microneedles on microneedle patches. The microneedle patches self-interlock on mechanically dynamic beating hearts, similar to honeybee stingers. The micro-bleeding and coagulation on the porous surface provide additional adhesion force. The microneedle patches attenuate left ventricular remodeling via mechanical support and are compatible with minimally invasive implantation.

Construction and properties of the silk fibroin and polypropylene composite biological mesh for abdominal incisional hernia repair.

Background: In this study, a new composite biological mesh named SFP was prepared by combining silk fibroin with polypropylene mesh. The mechanism and clinical application value of the SFP composite mesh were explored. Methods: The fibrous membrane was prepared by electrospinning of silk fibroin. The silk fibrous membrane was adhered to the polypropylene mesh by fibrin hydrogel to make a new composite mesh. The characterizations were verified by structural analysis and in vitro cell experiments. A total of 40 Sprague-Dawley rats were randomly divided into two groups, and 20 rats in each group were implanted with the SFP mesh and pure polypropylene mesh, respectively. The rats were sacrificed in batches on the 3rd, 7th, 14th, and 90th days after surgery. The adhesion degree and adhesion area on the mesh surface were compared, and a histopathological examination was carried out. Results: In vitro cell function experiments confirmed that the SFP mesh had good cell viability. The control group had different degrees of adhesion on the 3rd, 7th, 14th, and 90th days after surgery. However, there was almost no intraperitoneal adhesions on the 3rd and 7th days after surgery, and some rats only had mild adhesions on the 14th and 90th days after surgery in the SFP group. There were statistically significant differences in the postoperative intraperitoneal adhesion area and adhesion degree between the two groups (p < 0.05). Histopathological examination confirmed that the mesenchymal cells were well arranged and continuous, and there were more new capillaries and adipocyte proliferation under the mesenchymal cells in the SFP group. Conclusion: The SFP mesh shows good biocompatibility and biofunction in vitro and in vivo. It can promote the growth of peritoneal mesenchymal cells. The formation of a new mesenchymal cell layer can effectively reduce the extent and scope of adhesion between the mesh and abdominal organs. The SFP mesh will have a good application prospect in the field of abdominal wall hernia repair.

A Polymeric Strategy Empowering Vascular Cell Selectivity and Potential Application Superior to Extracellular Matrix Peptides.

Endothelialization of vascular implants plays a vital role in maintaining the long-term vascular patency. In situ endothelialization and re-endothelialization is generally achieved by selectively promoting endothelial cell (EC) adhesion and, meanwhile, suppressing smooth muscle cell (SMC) adhesion. Currently, such EC versus SMC selectivity is achieved and extensively used in vascular-related biomaterials utilizing extracellular-matrix-derived EC-selective peptides, dominantly REDV and YIGSR. Nevertheless, the application of EC-selective peptides is limited due to their easy proteolysis, time-consuming synthesis, and expensiveness. To address these limitations, a polymeric strategy in designing and finding EC-selective biomaterials using amphiphilic ß-peptide polymers by tuning serum protein adsorption is reported. The optimal ß-peptide polymer displays EC versus SMC selectivity even superior to EC-selective REDV peptide regarding cell adhesion, proliferation, and migration of ECs versus SMCs. Study of the mechanism indicates that surface adsorption of bovine serum albumin, an abundant and anti-adhesive serum protein, plays a critical role in the ECs versus SMCs selectivity of ß-peptide polymer. In addition, surface modification of the optimal ß-peptide polymer effectively promotes the endothelialization of vascular implants and inhibits intimal hyperplasia. This study provides an alternative strategy in designing and finding EC-selective biomaterials, implying great potential in the vascular-related biomaterial study and application.