Adhesive Biomaterials Research Articles

Bilayer Scaffolds of PLLA/PCL/CAB Ternary Blend Films and Curcumin-Incorporated PLGA Electrospun Nanofibers: The Effects of Polymer Compositions and Solvents on Morphology and Molecular Interactions.

Tissue engineering scaffolds have been dedicated to regenerating damaged tissue by serving as host biomaterials for cell adhesion, growth, differentiation, and proliferation to develop new tissue. In this work, the design and fabrication of a biodegradable bilayer scaffold consisting of a ternary PLLA/PCL/CAB blend film layer and a PLGA/curcumin (CC) electrospun fiber layer were studied and discussed in terms of surface morphology, tensile mechanical properties, and molecular interactions. Three different compositions of PLLA/PCL/CAB-60/15/25 (TBF1), 75/10/15 (TBF2), and 85/5/10 (TBF3)-were fabricated using the solvent casting method. The electrospun fibers of PLGA/CC were fabricated using chloroform (CF) and dimethylformamide (DMF) co-solvents in 50:50 and 60:40 volume ratios. Spherical patterns of varying sizes were observed on the surfaces of all blend films-TBF1 (17-21 µm) > TBF2 (5-9 µm) > TBF3 (1-5 µm)-caused by heterogeneous surfaces inducing bubble nucleation. The TBF1, TBF2, and TBF3 films showed tensile elongation at break values of approximately 170%, 94%, and 43%, respectively. The PLGA/CC electrospun fibers fabricated using 50:50 CF:DMF had diameters ranging from 100 to 400 nm, which were larger than those of the PLGA fibers (50-200 nm). In contrast, the PLGA/CC electrospun fibers fabricated using 60:40 CF:DMF had diameters mostly ranging from 200 to 700 nm, which were larger than those of PLGA fibers (200-500 nm). Molecular interactions via hydrogen bonding were observed between PLGA and CC. The surface morphology of the bilayer scaffold demonstrated adhesion between these two solid surfaces resembling "thread stitches" promoted by hydrophobic interactions, hydrogen bonding, and surface roughness.

Bottlebrush Thermoplastic Elastomers as Hot-Melt Pressure-Sensitive Adhesives.

Hot-melt pressure-sensitive adhesives (HMPSAs) are used in applications from office supplies to biomedical adhesives. The major component in HMPSA formulations is thermoplastic elastomers, such as styrene-based block copolymers, that provide both mechanical integrity and moldability. Since neat polymer networks are unable to establish an adhesive bond, large quantities of plasticizers and tackifiers are added. These additives enhance the adhesive performance but complicate the phase behavior and property stability of the pressure-sensitive adhesive. Herein, we introduce an alternative additive-free approach to HMPSA design based on self-assembly of bottlebrush graft-copolymers, where side chains behave as softness, strength, and viscoelasticity mediators. These systems maintain moldability of conventional thermoplastic elastomers, while architecturally disentangled bottlebrush network strands empower several benefits such as extreme softness for substrate wetting, low melt viscosity for molding and 3D-printing, and a broad frequency range of viscoelastic responses for adhesion regulation within almost four orders of magnitude. The brush graft-copolymers implement five independently controlled architectural parameters to regulate the Rouse time, work of adhesion, and debonding mechanisms.

S-Protected Thiolated Chitosan versus Thiolated Chitosan as Cell Adhesive Biomaterials for Tissue Engineering.

Chitosan (Ch) and different Ch derivatives have been applied in tissue engineering (TE) because of their biocompatibility, favored mechanical properties, and cost-effectiveness. Most of them, however, lack cell adhesive properties that are crucial for TE. In this study, we aimed to design an S-protected thiolated Ch derivative exhibiting high cell adhesive properties serving as a scaffold for TE. 3-((2-Acetamido-3-methoxy-3-oxopropyl)dithio) propanoic acid was covalently attached to Ch via a carbodiimide-mediated reaction. Low-, medium-, and high-modified Chs (Ch-SS-1, Ch-SS-2, and Ch-SS-3) with 54, 107 and 140 μmol of ligand per gram of polymer, respectively, were tested. In parallel, three thiolated Chs, namely Ch-SH-1, Ch-SH-2, and Ch-SH-3, were prepared by conjugating N-acetyl cysteine to Ch at the same degree of modification to compare the effectiveness of disulfide versus thiol modification on cell adhesion. Ch-SS-1 showed better cell adhesion capability than Ch-SS-2 and Ch-SS-3. This can be explained by the more lipophilic surfaces of Ch-SS as a higher modification was made. Although Ch-SH-1, Ch-SH-2, and Ch-SH-3 were shown to be good substrates for cell adhesion, growth, and proliferation, Ch-SS polymers were superior to Ch-SH polymers in the formation of 3D cell cultures. Cryogels structured by Ch-SS-1 (SSg) resulted in homogeneous scaffolds with tunable pore size and mechanical properties by changing the mass ratio between Ch-SS-1 and heparin used as a cross-linker. SSg scaffolds possessing interconnected microporous structures showed good cell migration, adhesion, and proliferation. Therefore, Ch-SS can be used to construct tunable cryogel scaffolds that are suitable for 3D cell culture and TE.

Renewable adhesives based on oleo-chemistry: From green synthesis to biomedical applications

Polyurethanes (PUs) are known as performing biomedical tissue adhesive materials. Adhesive applications can be based on synthesized PU-based prepolymers with highly reactive isocyanate (NCO) end-chains, which covalently react with surrounding living tissues. In this study, original sustainable macromolecular architectures were designed and tested. Different fully biobased polyfunctional NCO terminated prepolymers were synthesized from cotton oil (CO)-based polyols and different sustainable diisocyanates (l-Lysine ethyl ester diisocyanate (LDI), pentane diisocyanate (PDI) and dimeryl diisocyanate (DDI)). Then, two-component adhesive systems were prepared using the prepolymers and two chain extenders: 1,4-butanediol and 2-hydroxyethyl disulfide, to obtain in this latter case potential stimuli-responsive materials based on the disulfide bonds. Prepolymers' properties such as in-vitro biocompatibility, as well as two-components systems' adhesive behavior on muscle tissue were assessed. From these two-component systems, fully biobased PUs were obtained. The influence of the selected CO-based polyol, the diisocyanate and the chain extender on the physicochemical, thermal and mechanical properties of the corresponding PUs were studied. Moreover, their influence on biocompatibility and properties related to biomedical applications were discussed. The series of PUs exhibited a large range of properties such as Young's moduli at 25 and 37 °C, ranging from 0.4 to 22 MPa, and adequate hydrolytic and enzymatic degradations after nine weeks of incubation. LDI and PDI-based samples showed great interest in the preparation of such biomedical adhesives due to their good biocompatibilities.

Nano-enabled DNA supramolecular sealant for soft tissue surgical applications

Bioadhesives or sealants have received considerable attention for suture-less wound sealing. However, most adhesive biomaterials involve complex molecular designs which lack dynamic mechanical properties, inherent hemostasis, as well as the capability of preventing postsurgical tissue adhesion. Herein, a nano-enabled supramolecular hydrogel sealant based on complementary DNA duplexes combined with multiple physicochemical crosslinks is designed and demonstrated. This supramolecular sealant exhibits excellent dynamic reversibility, low swelling, and wet adhesive properties. It can achieve rapid sealing of damaged tissues, blood coagulation, as well as hemostasis. Furthermore, DNA molecules endow the sealant with promising capabilities of preventing protein absorption, cell adhesion and postsurgical tissue adhesion. The in vivo evaluation based on the gastric perforation repair model shows that the sealant can improve granulation tissue growth, collagen deposition, and vascularization and facilitate gastric perforation closure. The nano-enabled DNA supramolecular hydrogel sealant represents a promising alternative for gastric perforation repair and has large clinical potential pertaining to suture-less repair of soft tissues. Data availabilityThe data reported in this manuscript are available upon request.

Glycoproteins Involved in Sea Urchin Temporary Adhesion.

Biomedical adhesives, despite having been used increasingly in recent years, still face a major technological challenge: strong adhesion in wet environments. In this context, biological adhesives secreted by marine invertebrates have appealing characteristics to incorporate into new underwater biomimetic adhesives: water resistance, nontoxicity and biodegradability. Little is still known about temporary adhesion. Recently, a transcriptomic differential analysis of sea urchin Paracentrotus lividus tube feet pinpointed 16 adhesive/cohesive protein candidates. In addition, it has been demonstrated that the adhesive secreted by this species is composed of high molecular weight proteins associated with N-Acetylglucosamine in a specific chitobiose arrangement. As a follow-up, we aimed to investigate which of these adhesive/cohesive protein candidates were glycosylated through lectin pulldowns, protein identification by mass spectroscopy and in silico characterization. We demonstrate that at least five of the previously identified protein adhesive/cohesive candidates are glycoproteins. We also report the involvement of a third Nectin variant, the first adhesion-related protein to be identified in P. lividus. By providing a deeper characterization of these adhesive/cohesive glycoproteins, this work advances our understanding of the key features that should be replicated in future sea urchin-inspired bioadhesives.

Suppressed Migration and Enhanced Cisplatin Chemosensitivity in Human Cancer Cell Lines by Tuning the Molecular Mobility of Supramolecular Biomaterials.

Cancer cells recognize physical cues transmitted from the surrounding microenvironment, and accordingly alter the migration and chemosensitivity. Cell adhesive biomaterials with tunable physical properties can contribute to the understanding of cancer cell responses, and development of new cancer therapies. Previously, it was reported that polyrotaxane-based surfaces with molecular mobility effectively modulate cellular functions via the yes-associated protein (YAP)-related signaling pathway. In the present study, the impact of molecular mobility of polyrotaxane surfaces on the migration and chemosensitivity of lung (A549), pancreatic (BxPC-3), and breast cancer (MDA-MB-231) cell lines is investigated, and it is found that the cellular spreading of adherent A549 and BxPC-3 cells and nuclear YAP translocation are promoted on low-mobility surfaces, suggesting that cancer cells alter their subcellular YAP localization in response to molecular mobility. Furthermore, low-mobility surfaces suppress cellular migration more than high-mobility surfaces. Additionally, low-mobility surfaces promote the cisplatin chemosensitivity of each cancer cell line to a greater extent than high-mobility surfaces. These results suggest that the molecular mobility of polyrotaxane surfaces suppresses cellular migration and enhances chemosensitivity via the subcellular translocation of YAP in cancer cells. Biointerfaces based on polyrotaxanes can thus be a new platform for elucidating cancer cell migration and chemoresistance mechanisms.

Degradable Bioadhesives Based on Star PEG-PLA Hydrogels for Soft Tissue Applications.

Tissue adhesives are interesting materials for wound treatment as they present numerous advantages compared to traditional methods of wound closure such as suturing and stapling. Nowadays, fibrin and cyanoacrylate glues are the most widespread commercial biomedical adhesives, but these systems display some drawbacks. In this study, degradable bioadhesives based on PEG-PLA star-shaped hydrogels are designed. Acrylate, methacrylate, and catechol functional copolymers are synthesized and used to design various bioadhesive hydrogels. Various types of mechanisms responsible for adhesion are investigated (physical entanglement and interlocking, physical interactions, chemical bonds), and the adhesive properties of the different systems are first studied on a gelatin model and compared to fibrin and cyanoacrylate references. Hydrogels based on acrylate and methacrylate reached adhesion strength close to cyanoacrylate (332 kPa) with values of 343 and 293 kPa, respectively, whereas catechol systems displayed higher values (11 and 19 kPa) compared to fibrin glue (7 kPa). Bioadhesives were then tested on mouse skin and human cadaveric colonic tissue. The results on mouse skin confirmed the potential of acrylate and methacrylate gels with adhesion strength close to commercial glues (15-30 kPa), whereas none of the systems led to high levels of adhesion on the colon. These data confirm that we designed a family of degradable bioadhesives with adhesion strength in the range of commercial glues. The low level of cytotoxicity of these materials is also demonstrated and confirm the potential of these hydrogels to be used as surgical adhesives.

Supramolecular Adhesive Materials with Antimicrobial Activity for Emerging Biomedical Applications.

Traditional adhesives or glues such as cyanoacrylates, fibrin glue, polyethylene glycol, and their derivatives have been widely used in biomedical fields. However, they still suffer from numerous limitations, including the mechanical mismatch with biological tissues, weak adhesion on wet surfaces, biological incompatibility, and incapability of integrating desired multifunction. In addition to adaptive mechanical and adhesion properties, adhesive biomaterials should be able to integrate multiple functions such as stimuli-responsiveness, control-releasing of small or macromolecular therapeutic molecules, hosting of various cells, and programmable degradation to fulfill the requirements in the specific biological systems. Therefore, rational molecular engineering and structural designs are required to facilitate the development of functional adhesive materials. This review summarizes and analyzes the current supramolecular design strategies of representative adhesive materials, serving as a general guide for researchers seeking to develop novel adhesive materials for biomedical applications.

Mechanical, wear and thermal conductivity characteristics of snail shell-derived hydroxyapatite reinforced epoxy bio-composites for adhesive biomaterials applications

ABSTRACT This research investigates the effects of snail shell-based hydroxyapatite (HAp) reinforcements on the mechanical, wear, and selected physical properties of epoxy-based composites. The exploitation of these properties was aimed at assessing the suitability and efficiency of the developed bio-composites for adhesive biomedical applications. Snail shell wastes were sourced and processed to obtain (HAp) particles of ˂20 μm. The bio-derived hydroxyapatite-based epoxy composites were produced using the stir-cast method by mixing the hydroxyapatite with the epoxy resin and hardener before pouring into the moulds where they are allowed to cure. Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD) of the snail shell hydroxyapatite particles were carried out while mechanical, wear, and physical properties of the developed composites were evaluated. SEM images of the fracture surfaces were also examined. The results showed that enhancements occurred from the addition of snail shell-derived HAp to epoxy resin in the developed composites. The results revealed that most of the properties gave their optimum values when 15 wt.% reinforcement was used. At this weight fraction, optimum values were obtained which include 43 MPa for maximum flexural strength, 40HS for hardness, 40 J for impact, 0.35 W/mK for thermal conductivity, and 0.07 for wear index.

Trend Analysis for the Treatment of Incompetent GSV

Purpose: Chronic venous disease (CVD) has an excellent socioeconomic impact. Treatment modalities of CVD are evolving fields that could be derived from the disease's progressive nature. Materials and methods: After a wide literature search in Google Scholar (Publish and Perish software), extracted data was analyzed by VOSviewer software, creating network and overlay visualizations. Results: CVD has been investigated intensively in the literature from the beginning of the 21st century. Studies aimed to understand the mechanism of CVD in the early 2000s. Later, the focus of scientific interest was moved to novel procedures. Researchers were motivated to explore the reasons for technical failures and recurrences of endovenous thermal ablation (EVTA) procedures and open surgery to treat saphenous incompetence. Less invasive procedures replaced invasive open surgery. The search for novel tissue sealants showed a thin centralized network. Papers were dated from 2010. Therefore, this is a very recent source of evidence. There were meeting points for some components of tissue sealants. Biomaterials for novel tissue adhesion are under development and investigation. The efficacy and safe application in humans is the focus of research. Conclusion: Researchers widely investigate CVD. An evolution from invasive open surgery (stripping) through EVTA to non-thermal ablation procedures could be discovered in the literature. There could be some versatile options for replacing cyanoacrylate in the future, but there are no clear paths to reach that point in scientific literature yet.

Mechanistic understanding of catechols and integration into an electrochemically cross-linked mussel foot inspired adhesive hydrogel

Catechol reaction mechanisms form the basis of marine mussel adhesion, allowing for bond formation and cross-linking in wet saline environments. To mimic mussel foot adhesion and develop new bioadhesive underwater glues, it is essential to understand and learn to control their redox activity as well as their chemical reactivity. Here, we study the electrochemical characteristics of functionalized catechols to further understand their reaction mechanisms and find a stable and controllable molecule that we subsequently integrate into a polymer to form a highly adhesive hydrogel. Contradictory to previous hypotheses, 3,4-dihydroxy-L-phenylalanine is shown to follow a Schiff-base reaction whereas dopamine shows an intramolecular ring formation. Dihydrocaffeic acid proved to be stable and was substituted onto a poly(allylamine) backbone and electrochemically cross-linked to form an adhesive hydrogel that was tested using a surface forces apparatus. The hydrogel's compression and dehydration dependent adhesive strength have proven to be higher than in mussel foot proteins (mfp-3 and mfp-5). Controlling catechol reaction mechanisms and integrating them into stable electrochemically depositable macroscopic structures is an important step in designing new biological coatings and underwater and biomedical adhesives.

Oriented in situ immobilization of a functional tyrosinase on microcrystalline cellulose effectively incorporates DOPA residues in bioengineered mussel adhesive protein.

Catechol-containing polymers such as mussel adhesive proteins (MAPs) are attractive as biocompatible adhesive biomaterials, and the catecholic amino acid 3,4-dihydroxyphenyl-L-alanine (DOPA) is considered a key molecule in underwater mussel adhesion. Tyrosinases can specifically convert tyrosine to DOPA without any cofactors. However, their catalytic properties still need to be adjusted to minimize unwanted DOPA oxidation via their diphenolase activity and catechol instability at neutral and basic pH values in the reaction products. In this work, we constructed a novel functional tyrosinase, mTyr-CNK_CBM, by fusion of mTyr-CNK with a cellulose-binding motif (CBM) for oriented in situ immobilization on microcrystalline cellulose via the C-terminal CBM without any additional purification steps. mTyr-CNK_CBM showed optimal catalytic activity at pH 4.5-6.5 and room temperature and had a high monophenolase/diphenolase activity ratio (Vmax mono/Vmax di = 2.08 at pH 6 and 25°C). mTyr-CNK_CBM exhibited 2.17-fold higher (as a unimmobilized free enzyme) and similarly high (upon immobilization) in vitro DOPA modification of a bioengineered MAP compared to a commercially available mushroom tyrosinase. Moreover, the immobilized mTyr-CNK_CBM showed long-term storability and improved reusability. These results clearly demonstrate a strong potential for practical use of immobilized mTyr-CNK_CBM as a monophenol monooxygenase in preparing biocompatible DOPA-tethered biomaterials and other catechol-containing polymers.

Photocrosslinkable gelatin/collagen based bioinspired polyurethane-acrylate bone adhesives with biocompatibility and biodegradability

Hard or soft tissue adhesives have been presented as a promising candidate to replace traditional wound closure methods. However, there are mechanical strength problems in biological adhesives and biocompatibility problems in synthetic-based adhesives. At this point, we aimed to remove all these disadvantages and produce a single adhesive that contains all the necessary features and acrylate functionalized UV-curable polyurethane formulations were produced with high crosslink density, high adhesion strength, biocompatibility and injectable property for easy application as potential biomedical adhesives. Aliphatic isophorone diisocyanate (IPDI) was used as the isocyanate source and β-cyclodextrin was used for host-guest relationship with gentamicin by crosslinking. Proteins (gelatin (GEL), collagen (COL)) and PEGs of various molecular weight ranges (P200, P400, P600) were selected as the polyol backbone for polyurethane synthesis due to their multiple biological activities such as biocompatibility, biodegradability, biomimetic property. Several techniques have been used to characterize the structural, thermal, morphological, and various other physicochemical properties of the adhesive formulations. Besides, the possibility of its use as a hard tissue adhesive was investigated by evaluating the tissue adhesion strength in vitro and ex vivo via a universal testing analyzer in tensile mode. Corresponding adhesive formulations were evaluated by in vitro and in vivo techniques for biocompatibility. The best adhesion strength results were obtained as 3821.0 ± 214.9, and 3722.2 ± 486.8 kPa, for IPDI-COL-P200 and IPDI-GEL-P200, respectively. Good antibacterial activity capability toward Escherichia coli Pseudomonas aeruginosa, and Staphylococcus aureus were confirmed using disc diffusion method. Moreover, cell viability assay demonstrated that the formulations have no significant cytotoxicity on the L929 fibroblast cells. Most importantly, we finally performed the in vivo biodegradability and in vivo biocompatibility evaluations of the adhesive formulations on rat model. Considering their excellent cell/tissue viability, fast curable, strong adhesion, high antibacterial character, and injectability, these adhesive formulations have significant potential for tissue engineering applications.

Bio-adhesive catechol-modified chitosan wound healing hydrogel dressings through glow discharge plasma technique

For clinical traumas and surgeries, adhesives that can be used in humid environments is considerably challenging. Inspired by the adhesive proteins of mussel, a gallic acid-modified chitosan-based (CS-GA) hydrogel was prepared through discharge plasma technology, which was first reported to realise polysaccharide-macromolecule-grafted phenolic acids. CS-GA hydrogels with different grafting amounts were successfully prepared, and their structures were characterised using ultraviolet, 1H nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The modified material exhibited excellent antioxidant properties, which were verified using classical DPPH radical scavenging and reducibility experiments. CS-GA was oxidised in air under physiological conditions and cross-linked to form a hydrogel, with unusual toughness and adhesion properties. The high biocompatibility and haemocompatibility of this hydrogel were showed through cytotoxicity and haemolysis experiments. Furthermore, the abilities of the hydrogel to promote wound healing and haemostasis were evaluated using in vivo rat whole layer skin defect and liver haemorrhage models, respectively. These abilities can provide many possibilities for the development of multifunctional biomedical adhesives.

Factor XIII Cross-Linked Adhesive Chitosan Hydrogels.

Biomedical adhesives have been found to be an attractive alternative to suturing in several circumstances. However, to date most of the clinically approved formulations are based on synthetic and highly reactive toxic chemicals. In this work, we aimed to combine for the first time the bioactive properties of the cationic polysaccharide chitosan and its intrinsic electrostatic binding to negatively charged tissues with the biocompatible and clinically compliant enzymatic cross-linking scheme of fibrin glue. This synergistic activity led to the generation of a transglutaminase Factor XIII cross-linkable chitosan formulation with fast gelation kinetics, tunable mechanical properties, antibacterial activity, and strong adhesion to cartilage.

Self-healable poly(γ-glutamic acid)/chitooligosaccharide hydrogels via ionic and π-interactions

Poly(γ-glutamic acid) (γ-PGA) was chemically modified with dopamine (DA) to introduce catechol groups. The γ-PGA/DA conjugate was then simply mixed with cationic chitooligosaccharide (CHI-O) to induce gelation through intermolecular π-cation and ionic interactions. The gelation characteristics of the γ-PGA/DA/CHI-O mixtures were investigated according to the polymer concentration and CHI-O mixing ratio. The physically crosslinked γ-PGA/DA/CHI-O hydrogels exhibited excellent self-healing properties and injectability. In addition, the hydrogels showed an adhesive strength of >3 kPa on an egg membrane and >9 kPa on a glass slide. Therefore, the γ-PGA/DA/CHI-O hydrogels have great prospects as self-healing and tissue adhesive biomaterials.

Anchoring α-cyclodextrin-based polyrotaxanes to biological tissues via riboflavin-mediated photo-crosslinking

In the present study, photo-crosslinkable polyrotaxanes (PRXs) via riboflavins (RBFs) were designed for anchoring to biological tissues. In particular, PRXs with amino groups, in which multiple α-cyclodextrins (α-CDs) with amino groups were threaded onto a poly(ethylene glycol) chain end-capped with adamantane molecules, were synthesized. PRXs with ≥33 amino groups were crosslinked to form hydrogels after irradiation with UV-A light in the presence of RBFs. The time for gelation was approximately 15 min at the shortest. The PRX hydrogels showed excellent adhesion and spreading of mouse fibroblasts. Furthermore, when photo-crosslinking on a surface of porcine aorta as model tissues, the PRXs with amino groups strongly anchored to the tissues. Additionally, the PRXs with amino groups were confirmed to successfully close an incision in the tissues. Thus, photo-crosslinkable PRXs may be applied as supermolecule-based tissue adhesive biomaterials for repairing and regenerating biological tissues.

Comparative adhesion of chemically and physically crosslinked poly(acrylic acid)-based hydrogels to soft tissues

In the design of polymeric biomaterials for soft tissue adhesion, careful regulation of the interactions between the material and soft tissue is critical. In order to improve the efficacy of bioadhesives, a greater understanding of the relationship between their chemical design and resulting adhesion mechanisms is required. In this work, poly(acrylic acid) (PAA) was functionalised either through bromoalkene functionalisation via nucleophilic substitution or via 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM)-mediated conjugation. Novel PAA-based hydrogels were developed through different types (chemistry) of crosslinks and crosslinking mechanisms. Two of these gels were crosslinked through UV initiation using Irgacure 2959 as the photoinitiator, another gel used visible light-mediated crosslinking with eosin Y as the photoinitiator, and the final gel utilised physical crosslinking through the interaction between boronic acid moieties and the polysaccharide mannan. Oscillatory rheometry was used to characterise the mechanical properties of the different gels, including their gelation kinetics. Tensile testing was used to characterise the adhesion of the different gels to hydroxyl and methacrylate self-assembled monolayers (SAMs), as a means of studying adhesion to interfaces with defined surface chemistry. Finally, adhesion to soft tissues (porcine epicardium and keratinized gingiva) was studied through lap shear and tensile testing. Our results indicate a variety of factors responsible for hydrogel/soft tissue adhesion; these include the tissue mechanics, bulk mechanics of the gel, weak non-specific adhesion forces, and strong covalent bonding. Tests confirm the effect of tissue biochemistry on adhesion, with thiyl-bonded gels displaying particularly strong adhesion to tissues (particularly the epicardium). It is hoped that the results presented provide insight for the improved rational design of biomaterials for tissue adhesion.

Metronomic Photodynamic Therapy Using an Implantable Electronic Device, a Preclinical Experiment for Introducing Phototherapy into Cancer Treatments in Internal Organs

Introduction: In a modern aging society, people expect high-quality cancer treatment but don't want to impair their quality of life. These trends made us imagine the needs of a novel cancer treatment system. We intend to develop a less invasive, low-cost cancer treatment system by using an implantable electronic device and introducing photodynamic therapy (PDT) into the treatment of malignancies in internal organs, including HBP area. Methods: We combined wirelessly powered fingernail-size LED chip, and tissue adhesive biomaterials to develop suture-free, tissue-adhesive, wirelessly powered LED devices. As a preclinical experiment, we investigated the anti-tumor effect of low-power and long-term photodynamic therapy, termed metronomic PDT, by using this device for the mouse cancer model. The device was implanted subcutaneously beneath intradermal tumors on the back of mice, and the mice could move freely in the cage placed on the antenna board that enables continuous illumination on the tumor. During the ten days of treatment, a photosensitizer (photofrin) was administered intravenously for two times. Results: The mice receiving mPDT showed significant growth suppression of the tumor when compared to the control mice. There was no adverse reaction in the surrounding normal tissues of the treatment group. Also, this experiment showed the effectiveness of green light, which has yet to be used clinically in PDT for the treatment of solid tumors. Conclusions: Metronomic PDT using implantable optoelectronic devices can be applied safely into the treatment of HBP malignancies as a low cost and less invasive local treatment method.