Controllable Degradation Rate Research Articles

Biodegradable synthetic polymeric composite scaffold‐based tissue engineered heart valve with minimally invasive transcatheter implantation

Prosthetic heart valve replacement is the main treatment for valvular heart disease, but the existing artificial valves (mechanical or biological valve) have inherent disadvantages. Patients with mechanical valves require lifelong anticoagulation because of the high risk of thromboembolism, while the durability of biological valve is poor, which easily leads to calcification or lobular degeneration. Besides, they all lack the abilities of self‐repair and growth which are very important for adolescent patients with valvular heart disease. To overcome these shortcomings, the researchers developed tissue engineered heart valves (TEHV) with self‐repairing and remodeling capabilities, low immunogenicity, and great durability. The preparation of three‐dimensional porous scaffolds is the key step in the success of TEHV. Because of their easy processing, active chemical properties, great mechanical properties and controllable degradation rate, synthetic biodegradable polymers are widely used in the preparation of TEHV scaffolds. This review summarizes the types, properties and process techniques of biodegradable synthetic polymers, such as polycaprolactone, polyglycolic acid, polylactic acid, and polyhydroxyalkanoates currently used to prepare the TEHV scaffolds. This review also focuses on the composite methods and performance of synthetic polymer‐based composite scaffolds. The prospects and challenges of the clinical application for minimally invasive implantation of TEHV are also discussed.

Synthesis and properties of multi-armed enantiomeric polylactide-polycaprolactone block copolymers

The degradability of degradable polymers is the most important property to determine the lifetime of commercial applications. To control degradation rate and thermal properties, enantiomeric block copolymers with lactide and hydroxyl terminated multi-armed polycaprolactone were synthesized. Thermal properties of various copolymers were determined by DSC and TGA measurements and the morphological changes during enzymatic degradation were identified by atomic force microscopy. The rate of enzymatic degradation of copolymers was faster than that of each homopolymer while the formation of the stereocomplex between the enantiomeric PLAs (L, D type) resulted in the improvement of thermal properties and retardation of enzymatic degradation.

Plant Engineering: Precision Delivery of Multiscale Payloads to Tissue‐Specific Targets in Plants (Adv. Sci. 13/2020)

In article number 1903551, Benedetto Marelli and co-workers design a silk-based biomaterial to fabricate a microneedle-like device with controlled degradation rate in planta via tuning material composition. The device enables precise access to xylem, phloem, and other plant tissues, thus being capable of serving as a delivery tool to release cargo molecules and as a sampling tool for analysis of plants fluid.

Dual cross-linked honey coupled 3D antimicrobial alginate hydrogels for cutaneous wound healing.

We report potentiation of healing efficacy of alginate by value addition at its structural level. Dual crosslinked (ionically and covalently) sodium alginate hydrogel coupled with honey (HSAG) brings about an intermediate stiffness in the fabric, confers consistent swelling property and limits erratic degradation of the polymer which ultimately provides conducive milieu to cellular growth and proliferation. In this work honey concentrations in HSAGs are varied from 2% to 10%. FTIR, XRD and nanoindentation studies on the HSAGs exhibited physicochemical integrity. In vitro degradation study provided the crucial finding on 4% HSAG having controlled degradation rate up to 12days with a weight loss of 87.36±1.14%. This particular substrate also has an ordered crystalline surface morphology with decent cellular viability (HaCaT and 3T3) and antimicrobial potential against Methicillin Resistant Staphylococcus aureus (MRSA) and Escherichia coli. The in vivo wound contraction kinetics on murine models (4% HSAG treated wound contraction: 94.56±0.1%) has been monitored by both invasive (histopathology) and noninvasive (Swept Source Optical Coherence Tomography) imaging and upon corroborating them it evidenced that 4% HSAG treated wound closure achieved epithelial thickness resembling to that of unwounded skin. Thus, the work highlights structurally modified alginate hydrogel embedded with honey as a potential antimicrobial healing agent.

Development of Bioadhesive Biomaterials Based on Silk and Hyaluronic Acid

Silk fibroin can be derived from the silkworm Bombyx mori and it has the main properties for its use as bioadhesive biomaterial in medicine – biocompatibility, good mechanical properties and controllable degradation rate. On the other hand hyaluronic acid (HA) is an attractive polymer for biomedical applications, due to its biological and structural importance, as well as its ease of modification. Thus in this study, two types of silk raw materials for preparation of silk fibroin (SF) solutions were used. Obtained SF solutions with and without hyaluronic acid (HA) were cross-linked to form hydrogels. Widely used cross-linking agent glutaraldehyde (GTA) was used in this study. Two temperatures 37°C and 60°C were chosen to determine the effect of temperature on the cross-linking rate of the samples. The gelation time, swelling ratio and structural features of the adhesive were also studied.

Pulse-driven bio-triboelectric nanogenerator based on silk nanoribbons

Abstract Triboelectric nanogenerators (TENGs) convert mechanical energy into electrical energy, providing the possibility of self-powered implantable electronic devices. However, most implantable electronic devices still require an external power source. In addition, TENGs must have outstanding biocompatibility, biodegradability, and controllable degradation rate to prevent the need for a second surgery and avoid an inflammatory response. In this work, a silk nanoribbon (SNR)-based bio-TENG is fabricated using a nascent SNR film (SNRF) and regenerative silk fibroin film (RSFF). To maintain the original meso/nanoscale structure of silk, SNRs with a thickness of 0.38 nm are directly exfoliated from natural silk. RSFF and SNRF have different microstructure and work functions. The output performance of the bio-TENG with the maximum voltage, current, and power density (PD) reach up to 41.64 V, 0.5 μA, and 86.7 mW/m2, respectively. The lifetime of the TENG depends on post-treatment of the RSFF package. The raw materials of the proposed TENG, including silk and magnesium (Mg), are completely biodegradable and biocompatible in vitro. With its high sensitivity and the ability to generate power from just a human pulse, the all silk-based bio-TENG may be an attractive power source for implantable self-powered electronic devices, such as pacemakers and implantable sensors.

Therapeutic Devices: Implantable, Degradable, Therapeutic Terahertz Metamaterial Devices (Small 17/2020)

In article number 2000294, Juncheng Cao, Tiger H. Tao, and co-workers report a therapeutic terahertz metamaterial device that can be safely implanted into the body with a controllable degradation rate for simultaneous real-time drug release monitoring and in situ treatment.

Implantable, Degradable, Therapeutic Terahertz Metamaterial Devices.

Metamaterial (MM) sensors and devices, usually consisting of artificially structured composite materials with engineered responses that are mainly determined by the unit structure rather than the bulk properties or composition, offer new functionalities not readily available in nature. A set of implantable and resorbable therapeutic MM devices at terahertz (THz) frequencies are designed and fabricated by patterning magnesium split ring resonators on drug-loaded silk protein substrates with controllable device degradation and drug release rates. To demonstrate proof-of-concept, a set of silk-based, antibiotics-loaded MM devices, which can serve as degradable antibacterial skin patches with capabilities to monitor drug-release in real time are fabricated. The extent of drug release, which correlates with the degradation of the MM skin patch, can be monitored by analyzing the resonant responses in reflection during degradation using a portable THz camera. Animal experiments are performed to demonstrate the in vivo degradation process and the efficacy of the devices for antibacterial treatment. Thus, the implantable and resorbable therapeutic MM devices do not need to be retrieved once implanted, providing an appealing alternative for in-vivo sensing and in situ treatment applications.

A three-dimensional hyaluronic acid-based niche enhances the therapeutic efficacy of human natural killer cell-based cancer immunotherapy

Adoptive transfer of natural killer (NK) cells is becoming one of the most important parts of cancer immunotherapy. However, recent accomplishments have focused on the improvement of the targeting effects based on the engineering of chimeric antigen receptors (CARs) on cell surfaces. Despite the large quantity of therapeutic cells required for clinical applications, the technology for ex vivo expansion is not well developed. Herein, a three-dimensional (3D) engineered hyaluronic acid-based niche for cell expansion (3D-ENHANCE) is introduced. Compared with the conventional two-dimensional (2D) method, NK-92 cell lines and human EGFR-specific (CAR)–NK cells cultured in 3D-ENHANCE yield favorable mRNA expressions, elevated cytokine release, upregulated proliferative and tumor-lytic abilities, and result in enhanced antitumor efficacy. Furthermore, controllable degradation rates can be realized by tuning the formulation of 3D-ENHANCE so that it can be applied as an implantable cell reservoir at surgical sites. In vivo results with the incompletely resected MDA-MB-231 model confirm that the peri-operative implantation of 3D-ENHANCE prevents the relapse and metastases after surgery. Overall, 3D-ENHANCE presents an effective cytokine-free niche for ex vivo expansion and postsurgical treatment that enhances the low-therapeutic efficacy of human NK cells.

Experimental Assessment of New Generation of Ureteral Stents: Biodegradable and Antireflux Properties.

Objective: The aim was to assess a new biodegradable and antireflux intraureteral stent (BraidStent®) design in a swine model after ureteral laparoscopic operation. Materials and Methods: A total of 24 female pigs underwent initial endoscopic, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Afterward, unilateral ureteropelvic junction obstruction was performed by laparoscopic approach. Six weeks later, the animals underwent laparoscopic Anderson-Hynes pyeloplasty, and were randomly assigned to Group-I, in which a double-pigtail ureteral stent was inserted for 6 weeks, or Group-II, in which a BraidStent®, a biodegradable intraureteral stent design, was placed. Follow-up assessments were performed at 3 and 6 weeks and 5 months. Results: In terms of therapeutic success, complete resolution was observed in 91.6% of Group-I animals and 88.8% in Group-II. No evidence of vesicoureteral reflux (VUR) was observed in Group-II animals and statistical significance in VUR and ureteral orifice damage were observed between groups. BraidStent® degradation occurred in a controlled manner between 3 and 6 weeks, without obstructive fragments. Distal ureteral peristalsis was maintained in 66.6% and 83.3% in Group-II at 3 and 6 weeks of follow-up, respectively. In Group-II, the positive bacteriuria rate was 41.6% and the migration rate 25%. Pathological assessment showed a significant improvement in ureteral healing in Group-II vs Group-I. Conclusions: The results of this comparative study in a porcine model indicate that the intraureteral BraidStent performed similarly to conventional ureteral stents. It avoids complete ureteral length intubation, the adverse effects associated with conventional ureteral stents, and maintains a high level of distal ureteral peristalsis. Moreover, the BraidStent® exhibited a predictable and controlled degradation rate and did not cause any obstructive fragments. However, further studies are needed to improve the anchoring system and reduce the risk of bacterial colonization.

Photo-Crosslinkable Double-Network Hyaluronic Acid Based Hydrogel Dressing

Hyaluronic acid (HA)-based hydrogels are widely used in biomedical applications due to their excellent biocompatibility and enzymatic degradability. In this paper a photo-crosslinking double-network hyaluronic acid-based hydrogel dressing was proposed. Hyaluronic acid can be UV-crosslinked by modification with methacrylic anhydride (HA-MA) and disulfide-crosslinked by modification with 3,3'-dithiobis (propionylhydrazide) (DTP) (HA-SH). The mixings of these two materials at different ratios were produced. All the samples can be quickly gelled at 365 nm for 10 s. The rheological tests show that the storage modulus (G') of the double network (HA-SH/HA-MA) hydrogel is increased with the increase of HA-SH content. The HA-SH/HA-MA hydrogel has porous structure, high swelling ratio and Controlled degradation rate. In vitro degradation tests show that the ratio of HA-SH/HA-MA ratio was 9:1 (S9M1) in 100 U/ml hyaluronidase (Hase) degraded by 89.91±2.26% at 11d. The cytocompatibility of HA-SH/HA-MA hydrogels was proved by Live/Dead stainings and CCK-8 assays in the human dermis fibroblasts (HDF) cells test. All these results highlight the biological potential of the HA-SH/HA-MA hydrogels for DFU intervention.

Machine learning as a tool to design glasses with controlled dissolution for healthcare applications

The advancement of glass science has played a pivotal role in enhancing the quality and length of human life. However, with an ever-increasing demand for glasses in a variety of healthcare applications – especially with controlled degradation rates – it is becoming difficult to design new glass compositions using conventional approaches. For example, it is difficult, if not impossible, to design new gene-activation bioactive glasses, with controlled release of functional ions tailored for specific patient states, using trial-and-error based approaches. Notwithstanding, it is possible to design new glasses with controlled release of functional ions by using artificial intelligence-based methods, for example, supervised machine learning (ML). In this paper, we present an ensemble ML model for reliable prediction of time- and composition-dependent dissolution behavior of a wide variety of oxide glasses relevant for various biomedical applications. A comprehensive database, comprising of over 1300 data-records consolidated from original glass dissolution experiments, has been used for training and subsequent testing of prediction performance of the ML model. Results demonstrate that the ensemble ML model can predict chemical degradation behavior of glasses in aqueous solutions over a wide range of pH relevant for their usage in a human body where the environment can be highly acidic (for example, pH = 3), for example, due to secretion of citric acid by osteoclasts, or highly alkaline (pH ≈10) due to the release of alkali cations from bioactive glasses. Outcomes of this study can be leveraged to design glasses with controlled dissolution behavior in various biological environments. Statement of SignificanceIn this paper, we present an ensemble machine learning (ML) model for prediction of dissolution behavior of a wide variety of oxide glasses relevant for various biomedical applications. The results demonstrate that the ML model can predict the chemical degradation behavior of glasses in aqueous solutions over a wide range of pH relevant for their usage in a human body where the environment can be highly acidic (for example, pH = 3), for example, due to secretion of citric acid by osteoclasts, or highly alkaline (pH ≈10) due to the release of alkali cations from bioactive glasses. Outcomes of this study can be leveraged to design new biomedical glasses with controlled (desired) dissolution behavior in various biological environments.

Controllable Soil Degradation Rate of 5-Substituted Sulfonylurea Herbicides as Novel AHAS Inhibitors.

Chlorsulfuron has been applied in wheat fields as a recognized herbicide worldwide, yet it was officially banned in China since 2014 for its soil persistence problem. On the basis of our previous research that 5-dimethylamino distinctively accelerated degradation rate in soils, a modified amino moiety (Ia-c) and monosubstituted amino group (Id-e) were introduced onto the fifth position of the benzene ring in sulfonylurea structures, as well as heterocyclic amino substituents (If-g) to seek a suitable soil degradation rate during such an in situ crop rotation system. Referring to the biological data and ScAHAS inhibition and ScAHAS docking results, they turned out to be AHAS inhibitors with high potent herbicidal activities. The various influence on soil degradation rate along with crop safety indicated that different substituents on the fifth position have exerted an apparent impact. Their united study of structure-activity-safety-degradation relationship has great potential to provide valuable information for further development of eco-friendly agrochemicals.

Long-term study on the osteogenetic capability and mechanical behavior of a new resorbable biocomposite anchor in a canine model

BackgroundBiodegradable suture anchors are commonly used for repairing torn rotator cuffs, but these biodegradable materials still suffer from low mechanical strength, poor osteointegration, and the generation of acidic degradation byproducts. MethodThe purpose of this study was to evaluate the long-term mechanical behavior and osteogenetic capabilities of a biocomposite anchor injection molded with 30% β-tricalcium phosphate microparticles blended with 70% poly (L-lactide-co-glycolide) (85/15). This study investigated in vitro degradation and in vivo bone formation in a canine model. The initial mechanical behavior, mechanical strength retention with degradation time, and degradation features were investigated. ResultsThe results showed that the biocomposite anchor had sufficient initial mechanical stability confirmed by comparing the initial shear load on the anchor with the minimum shear load borne by an ankle fracture fixation screw, which is considered a worst-case implantation site for mechanical loading. The maximum shear load retention of the biocomposite anchor was 83% at 12 weeks, which is desirable, as it aligns with the rate of bone healing. The β-tricalcium phosphate fillers were evenly dispersed in the polymeric matrix and acted to slow the degradation rate and improve the mechanical strength of the anchor. The interface characteristics between the β-tricalcium phosphate particles and the polymeric matrix changed the degradation behavior of the biocomposite. Phosphate buffer saline was shown to diffuse through the interface into the biocomposite to inhibit the core accelerated degradation rate. In vivo, the addition of β-tricalcium phosphate induced new bone formation. The biocomposite material developed in this study demonstrated improved osteogenesis in comparison to a plain poly (L-lactide-co-glycolide) material. Neither anchor produced adverse tissue reactions, indicating that the biocomposite had favorable biocompatibility following long-term implantation. ConclusionIn summary, the new biocomposite anchor presented in this study had favorable osteogenetic capability, mechanical property, and controlled degradation rate for bone fixation. Translational potential of this articleThe new biocomposite anchor had sufficient initial and long-term fixation stability and bone formation capability in the canine model. It is indicated that the new biocomposite anchor has a ​potential for orthopedic application.

A waterborne polyurethane 3D scaffold containing PLGA with a controllable degradation rate and an anti-inflammatory effect for potential applications in neural tissue repair.

Currently, implanting tissue engineering scaffolds is one of the treatment methods for the regeneration of damaged tissues. The matching of the degradation rate of the scaffolds with the regeneration rate of the damaged zone is a big challenge in tissue engineering. Here, we have synthesized a series of biodegradable waterborne polyurethane emulsions and fabricated three-dimensional (3D) connected porous polyurethane scaffolds by freeze-drying. The degradation rate of the scaffolds was controlled by adjusting the relative ratio of poly-ε-caprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) in the soft segment. The degradation rate of the scaffolds gradually accelerated with the increase of the relative proportion of PLGA. By co-culture with BV2 microglia, the scaffolds promoted the differentiation of BV2 into an anti-inflammatory M2 phenotype rather than a pro-inflammatory M1 phenotype as the proportion of PLGA increases. When the BV2 cells were stimulated with lipopolysaccharide (LPS), the scaffolds with a higher PLGA ratio showed a much stronger anti-inflammatory effect. Then, we demonstrated that the scaffolds could promote the PC12 neurons to differentiate into neurites. Therefore, we believe that the polyurethane scaffolds have a promising potential application in neural tissue repair.

Development of rare-earth oxide reinforced magnesium nanocomposites targeting biomedical applications

This study deals with magnesium-based materials, considered as potential biodegradable implants that degrade within the body after curing the wound and restoring the bone tissue. Magnesium based materials need favorable mechanical and corrosion properties to be implanted inside the human body. Magnesium despite having good mechanical properties if immersed in a corrosive environment would tend to lose its mechanical integrity. The role of cerium oxide (CeO2) nanoparticles and zinc (Zn) an alloying element in improving the mechanical and corrosive properties of the base material will be studied to find its scope in orthopedic applications. The aim of the current work is to synthesize Mg/CeO2 and Mg-Zn/CeO2 nanocomposites by powder metallurgy method. Significant grain refinement and increase in hardness is noticed for both the nanocomposites due to the fair distribution of cerium nanoparticles. The room temperature compressive yield strength and ultimate compressive strength for Mg/CeO2 and Mg-Zn/CeO2 nanocomposites were higher than pure Mg. The addition of 1.0 vol% of CeO2 to pure Mg and Mg-0.5 vol% of Zn system showed controlled degradation rate in Hank’s balanced salt solution (HBSS) for 1, 2, 3, 4 and 7 days respectively.

“From the Nature for the Nature”: An Eco-Friendly Antifouling Coating Consisting of Poly(lactic acid)-Based Polyurethane and Natural Antifoulant

“From the nature, for the nature” is an instructive strategy to develop environment-friendly antifouling coatings. In this work, bio-sourced poly(lactic acid)-based polyurethane with hydrolyzable triisopropylsilyl acrylate (TSA) side groups has been prepared via thiol–ene reaction and polyaddition. Such a polymer exhibits high adhesion strength (∼2.0 MPa) and a controlled degradation rate tuned by varying its soft segment and TSA content. An environment-friendly coating is prepared with the polymer and an eco-friendly antifoulant (butenolide) derived from marine bacteria. Our study shows that butenolide can be released from the coating in continuous manner with a controlled rate as the polymer degrades in seawater. Digital holographic microscopy tracking analysis demonstrates that the coating can effectively inhibit the adhesion of marine bacteria Pseudomonas sp. Marine field test shows that such coating has excellent antifouling ability for more than 3 months.

Dual-Functioning Scaffolds for the Treatment of Spinal Cord Injury: Alginate Nanofibers Loaded with the Sigma 1 Receptor (S1R) Agonist RC-33 in Chitosan Films.

The present work proposed a novel therapeutic platform with both neuroprotective and neuroregenerative potential to be used in the treatment of spinal cord injury (SCI). A dual-functioning scaffold for the delivery of the neuroprotective S1R agonist, RC-33, to be locally implanted at the site of SCI, was developed. RC-33-loaded fibers, containing alginate (ALG) and a mixture of two different grades of poly(ethylene oxide) (PEO), were prepared by electrospinning. After ionotropic cross-linking, fibers were incorporated in chitosan (CS) films to obtain a drug delivery system more flexible, easier to handle, and characterized by a controlled degradation rate. Dialysis equilibrium studies demonstrated that ALG was able to form an interaction product with the cationic RC-33 and to control RC-33 release in the physiological medium. Fibers loaded with RC-33 at the concentration corresponding to 10% of ALG maximum binding capacity were incorporated in films based on CS at two different molecular weights—low (CSL) and medium (CSM)—solubilized in acetic (AA) or glutamic (GA) acid. CSL- based scaffolds were subjected to a degradation test in order to investigate if the different CSL salification could affect the film behavior when in contact with media that mimic SCI environment. CSL AA exhibited a slower biodegradation and a good compatibility towards human neuroblastoma cell line.

Dual-modal non-invasive imaging in vitro and in vivo monitoring degradation of PLGA scaffold based gold nanoclusters.

Biodegradable scaffolds play an important role in tissue engineering, and appropriate degradation and resorption rates of these scaffolds are necessary to accommodate tissue growth. Synthetic polymers are frequently used because of their ease of production, good biocompatibility and controllable degradation rates. However, monitoring the degradation of these polymers in vivo by a noninvasive approach remains limited. In this study, we designed a composite scaffold by labeling poly(lactic-co-glycolic acid) (PLGA) with gold nanoclusters (Au NCs), which were used for tracking in vivo degradation through dual-modal fluorescence/computed tomography (CT) imaging. The diameter of the Au NCs was approximately 2.5 nm, and the emission peak was at a wavelength of 700 nm. After labeling PLGA with the Au NCs, the fluorescence intensity of the Au NC/PLGA composite scaffold reached 9.0 × 109 (p/s/cm2/sr)/(μW/cm2), and the CT density of the scaffold increased to 200 HU. After the composite scaffold was implanted subcutaneously into nude mice, a continuous decrease in the fluorescence signal and CT value was observed. The mean fluorescence intensity was 8.3 × 109, 3.17 × 109, 2.26 × 109, 2.11 × 109, and 1.82 × 109 (p/s/cm2/sr)/(μW/cm2) from the first week to the fifth week, respectively. The mean CT value changed from 222.6 to 185.9, 149.1, 112.5, and 55.2 (Hounsfield unit, HU) at the different timepoints. Compared with the change in the fluorescence intensity, the change in the CT value was similar to the change in the weight, and the Pearson correlation coefficient between the change in the CT value and weight was 0.8626. Furthermore, the structure and morphology of the scaffolds at different timepoints were analyzed by three-dimensional (3-D) reconstruction. This novel method of noninvasive dynamic monitoring of biodegradable polymers in vivo provides insight into choosing suitable biomaterials for tissue engineering and regenerative medicine.

A biodegradable multifunctional porous microsphere composed of carrageenan for promoting imageable trans-arterial chemoembolization

Trans-arterial chemoembolization (TACE) has been a mainstream treatment for hepatocellular carcinoma (HCC), accordingly there are more requirements for embolic agents’ properties, mainly concentrated on biodegradability and imaging function. A new kind of biodegradable multifunctional porous microspheres (BMPMs) with internal coarse plications are ingeniously designed and manufactured, consisting of carrageenan, inhexol and superparamagnetic iron oxide nanoparticle (SPIO). BMPMs’ sound roundness and excellent swelling behavior guarantee them to be smoothly transported into appointed arteries’ ends and achieve satisfactory embolization effect. Porous structure together with sulphate groups on BMPMs’ skeleton weaved by cross-linked carrageenan contributes to a marvelous doxorubicin hydrochloride (Dox) loading capacity over 45 mg Dox per mL of swollen microspheres, as well as a controllable degradation rate by allowing enzymes to infiltrate into BMPMs through holes, degrading 20–35% after two months in vitro. Inner coarse plications enable BMPMs to effectively combine with iohexol via hydrophilic effect and SPIO by blocking, which can further exhibit a decent imaging performance under digital subtraction system (DSA) and magnetic resonance imaging (MRI) for optimization of current TACE and development of a more advanced imageable TACE (iTACE). Safety evaluation and animal experiment manifest that BMPMs are reliable enough and hold great potential and competitiveness of being used in curing HCC.