Fabrication of atelocollagen-coated bioabsorbable suture and the evaluation of its regenerative efficacy in Achilles tendon healing using a rat experimental model.

Recently, the incidence of Achilles tendon ruptures (ATRs) has become more common, and repair surgery using a bioabsorbable suture is generally preferred, particularly in the case of healthy patients. Sutures composed of poly(lactic-co-glycolic acid) (PLGA) are commonly used in ATR surgeries. Nevertheless, owing to the inherent limitations of PLGA, novel bioabsorbable sutures that can accelerate Achilles tendon healing are sought. Recently, several studies have demonstrated the beneficial effects of atelocollagen on tendon healing. In this study, poly(3,4-dihydroxy-L-phenylalanine) (pDOPA), a hydrophilic biomimetic material, was used to modify the hydrophobic surface of a PLGA suture (Vicryl, VC) for the stable coating of atelocollagen on its surface. The main objective was to fabricate an atelocollagen-coated VC suture and evaluate its performance in the healing of Achilles tendon using a rat model of open repair for ATR. Structural analyses of the surface-modified suture indicated that the collagen was successfully coated on the VC/pDOPA suture. Postoperative in vivo biomechanical analysis, histological evaluation, ultrastructural/morphological analyses, and western blotting confirmed that the tendons in the VC/pDOPA/Col group exhibit superior healing than those in the VC and VC/pDOPA groups after 1 and 6 weeks following the surgery. The this study suggests that atelocollagen-coated PLGA/pDOPA sutures are preferable for future medical applications, especially in the repair of ATR.

Eco-friendly silk fibroin/tannic acid coacervates for humid and underwater wood adhesives.

Bioadhesives derived from biomass are steadily gaining spotlight as substitutes for formaldehyde-based resins in the adhesive industry. However, there is a need to develop novel water-resistant bioadhesives with high adhesive and cohesive strengths because the currently available biomaterial-based adhesives have low mechanical strength. In this study, a complex coacervate was prepared easily by mixing silk fibroin and tannic acid to produce a bioadhesive with high adhesive and cohesive strengths as well as water resistance. The silk fibroin-tannic acid coacervate adhered well to various substrates, and its adhesive strength according to the type of substrate and water contact angle were evaluated comparatively. In particular, the adhesive strength of this adhesive on a wood substrate was systematically analyzed by varying different experimental parameters (relative humidity, surface roughness of the substrate, water stability, and pH). This cost-effective coacervate is applicable as an eco-friendly wood adhesive.

pH-sensitive gallol-rich chitosan hydrogel beads for on-off controlled drug delivery.

Malignant tumors have emerged as a serious health issue, and the interest in developing pH-sensitive polymers for site-specific drug delivery has increased. The physical and/or chemical properties of pH-sensitive polymers depend on the pH, and thus, drugs can be released by cleaving dynamic covalent and/or noncovalent bonds. In this study, gallic acid (GA) was conjugated to chitosan (CS) to prepare self-crosslinked hydrogel beads containing Schiff base (imine bond) crosslinks. The CS-GA hydrogel beads were formed by the dropwise addition of the CS-GA conjugate solution into a Tris-HCl buffer solution (TBS, pH 8.5). The pH-sensitivity of pristine CS was significantly enhanced following the introduction of GA moiety, and as a result, the CS-GA hydrogel beads swelled more than approximately 5000 % at pH 4.0, indicating an excellent swelling/deswelling ability of the beads at different pH (pH 4.0 and 8.5). The reversible breakage/recovery of the imine crosslinks in the CS-GA hydrogel beads was confirmed through X-ray photoelectron spectroscopic and rheological studies. Finally, Rhodamine B was loaded onto the hydrogel beads as a model drug to investigate the pH-sensitive drug release behavior. At pH 4, the drug was released up to approximately 83 % within 12 h. The findings indicate that the CS-GA hydrogel beads have great potential as a drug delivery system that is sensitive to acidic tumor sites in the body.

Ecofriendly poly(3-hydroxybutyrate-co-4-hydroxybutyrate) microbeads for sanitary products.

In the past, plastic microbeads (MBs) were added to personal healthcare products to improve the cleaning and exfoliating effects, but these have been withdrawn owing to their non-degradable nature and contribution to the pollution of marine environment, especially that caused by the adsorption of persistent organic pollutants (POPs) on MBs. Therefore, natural biodegradable alternatives are being developed, but these often do not exhibit sufficient performance to replace non-degradable MBs. In this study, poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB-4HB), a biodegradable aliphatic polyester, was used to prepare MBs via melt-electrospraying. We carried out the rheological characterization of P3HB-4HB with respect to melting temperature, and the melt-electrospray process was optimized to prepare MBs having sizes similar to those of commercially available MBs. Furthermore, the adsorption properties of the P3HB-4HB MBs for POPs were investigated. Unlike commercial MBs, the P3HB-4HB MBs adsorbed significantly fewer contaminants owing to their smooth and regular surfaces. Finally, a cleansing product containing P3HB-4HB MBs was prepared to evaluate their cleaning ability, and we found that the MB-based product could remove dirt and contaminants that were not easily removed by water alone. Thus, the biodegradable P3HB-4HB MBs have great potential for use as sustainable additives for cosmetic products for skin exfoliation.

Tannic-Acid-Enriched Poly(vinyl alcohol) Nanofibrous Membrane as a UV-Shie lding and Antibacterial Face Mask Filter Material.

Face masks are increasingly important in the battle against infectious diseases and air pollution. Nanofibrous membranes (NFMs) are promising filter layers for removing particulate matter (PM) without restricting air permeability. In this study, tannic-acid-enriched poly(vinyl alcohol) (PVA-TA) NFMs were fabricated by electrospinning PVA solutions containing large amounts of tannic acid (TA), a multifunctional polyphenol compound. We were able to prepare uniform electrospinning solution without coacervate formation by inhibiting the robust hydrogen bonding between PVA and TA. Notably, the NFM maintained its fibrous structure even under moist conditions after heat treatment without the use of a cross-linking agent. Further, the mechanical strength and thermal stability of the PVA NFM were improved by the introduction of TA. The functional PVA NFM with a high TA content showed excellent UV-shielding (UV-A: 95.7%, UV-B: 100%) and antibacterial activity against Escherichia coli (inhibition zone: 8.7 ± 1.2 mm) and Staphylococcus aureus (inhibition zone: 13.7 ± 0.6 mm). Moreover, the particle filtration efficiency of the PVA-TA NFM for PM0.6 particles was 97.7% at 32 L min-1 and 99.5% at 85 L min-1, indicating excellent filtration performance and a low pressure drop. Therefore, the TA-enriched PVA NFM is a promising mask filter layer material with excellent UV-blocking and antibacterial properties and has the potential for various practical applications.

Cobalt ion-mediated cysteine detection with a hyperbranched conjugated polyelectrolyte as a new sensing platform.

A highly efficient colorimetric and fluorescence turn-off probe for the sensitive and selective detection of the biologically important amino acid, cysteine (Cys), is demonstrated using a newly synthesized water-soluble hyperbranched polymer (HP) containing sulfonic acid groups. The detection mechanism involves two steps: (i) the slight quenching of HP in the presence of Co(2+) in advance; and (ii) the gradual quenching of the HP-Co(2+) complex according to the concentration of Cys due to the absorption screening effect of the formation of the Cys-Co(2+) complex, which prevents HP from absorbing excitation energy.

Poly(vinyl alcohol) nanofibrous membranes via green electrospinning and tannin coating for selective removal of Pb(II) ion.

The conventional adsorbent fabrication methods involve complicated processes and may cause secondary contaminations. Therefore, an effective eco-friendly method is required for the fabrication of heavy metal adsorbents using inexpensive and eco-friendly materials without secondary pollution during their process. In this study, nanofibrous membranes (NFMs) were fabricated via green electrospinning of poly(vinyl alcohol) (PVA), a hydrophilic polymer, and their water resistance was improved through simple heat treatment without using additional additives. Then, nanofibrous heavy metal adsorbents were prepared by dip-coating the NFMs in an aqueous solution of tannic acid (TA), a natural polyphenol. First, the adsorption/desorption behavior of TA on PVA NFMs during the TA coating process was investigated. In addition, the effects of TA coating on the mechanical properties and heavy metal adsorption characteristics of the PVA NFMs were analyzed. The TA coating significantly increased the mechanical strength, heat resistance, and heavy metal (Pb(II)) adsorption capacity of the PVA NFM. The Pb2+ adsorption amount of TA-coated PVA NFMs exhibited about 5-7 times higher than those of other heavy metal ions, indicating excellent selectivity for Pb2+. In addition, the TA-coated PVA NFMs retained >70% of its initial adsorption capacity even after four cycles of adsorption/desorption, indicating its reusability.

Mussel-inspired poly(γ-gl utamic acid)/nanosilicate composite hydrogels with enhanced mechanical properties, tissue adhesive properties, and skin tissue regeneration.

It was demonstrated herein that the adhesive property of catechol-functionalized nanocomposite hydrogel can be enhanced by tuning the cohesive strength due to the secondary crosslinking between catechol and synthetic bioactive nanosilicate, viz. Laponite (LP). The nanocomposite hydrogel consists of the natural anionic poly(γ-glutamic acid) (γ-PGA), which was functionalized with catechol moiety, and incorporated with disk-structured LP. The dual-crosslinked hydrogel was fabricated by enzymatic chemical crosslinking of catechol in the presence of horseradish peroxidase (HRP) and H2O2, and physical crosslinking between γ-PGA-catechol conjugate and LP. The PGADA/LP nanocomposite hydrogels with catechol moieties showed strong adhesiveness to various tissue layers and demonstrated an excellent hemostatic properties. These PGADA/LP nanocomposite hydrogels are potentially applied for injectable tissue engineering hydrogels, tissue adhesives, and hemostatic materials. STATEMENT OF SIGNIFICANCE: Recently, many attempts have been performed to manufacture high-performance tissue adhesives using synthetic and natural polymer-based materials. In order to apply in various biological substrates, commercially available tissue adhesives should have an improved adhesive property in wet conditions. Here, we designed a mussel-inspired dual crosslinked tissue adhesive that meets most of conditions as an ideal tissue adhesive. The designed tissue adhesive is composed of poly(γ-glutamic acid)-dopamine conjugate (PGADA)-gluing macromer, horseradish peroxidase (HRP)/hydrogen peroxide (H2O2)-enzymatic crosslinker, and Laponite (LP)-additional physical crosslinking nanomaterial. The PGADA hydrogel has tunable physicochemical properties by controlling the LP concentration. Furthermore, this dual crosslinked hydrogel shows strong tissue adhesive property, regardless of the tissue types. Specially the PGADA hydrogel has tissue adhesive strength four times higher than commercial bioadhesive. This dual crosslinked PGADA hydrogel with improved tissue adhesion property is a promising biological tissue adhesive for various tissue type in surgical operation.

Self-crosslinkable hyaluronate-based hydrogels as a soft tissue filler.

With increasing interest in aging and skin care, the use of fillers to increase the volume of soft tissue volume is increasing globally. However, the side effects caused by the residual chemical crosslinking agents present in these fillers limit the effective application of commercialized filler products. Therefore, the development of a novel crosslinking system with a non-toxic chemical crosslinking agent is required to overcome the limitations of commercial hyaluronate (HA)-based fillers. In this paper, a new injectable hydrogel with enhanced mechanical properties, tissue adhesion, injectability, and biocompatibility is reported. The HA derivatives modified with catechol groups (HA-DA) were crosslinked by self-oxidation under in vivo physiological conditions (pH 7.4) without chemical crosslinkers to form hydrogels, which can be further accelerated by the dissolved oxygen in the body. The fabricated HA-DA filler showed excellent mechanical properties and could be easily injected with a low injection force. Further, the HA-DA filler stably attached to the injection site due to the tissue adhesion properties of the catechol groups, thus leading to an improved displacement stability. In addition, the HA-DA filler showed excellent cell viability, cell proliferation, and biocompatibility. Therefore, the HA-DA hydrogel is a novel soft tissue filler with great potential to overcome the limitations of commercial soft tissue fillers.

Synthesis and electrostatic nano-assembly of water-soluble polybenzothiadiazole derivatives with long-wavelength emission in the solid states.

We have synthesized APBT and APTBT containing benzothiadiazole units by Suzuki cross-coupling reaction with good yield. The polymers showed blue emission colors in aqueous solutions, while long wavelength shift was observed in the solid state due to facilitated exciton migration. APBT and APTBT are water-soluble and highly-fluorescent conjugated polymers with negatively charged sulfonate side chains and thus they can be electrostatically assembled with oppositely charged polyelectrolyte such as cationic polymer, poly(dimethyldiallylammonium chloride) (PDAC) via layer-by-layer (LbL) deposition technique on a glass slide. According to the increased the number of bilayer, we found that the assembled film exhibited larger enhancement of the long wavelength emission relative to the blue emission, due to the increased excition migration.

Aliphatic Polyester-Based Biodegradable Microbeads for Sustainable Cosmetics.

Marine pollution stemming from plastic microbeads (MBs) in personal care products has been substantially increased because of their nonbiodegradability and high adsorption capacity against persistent organic pollutants (POPs) in seawater. Moreover, the manufacturing process of MBs has been based on wet processes, such as emulsification, microfluidics, and precipitation. Therefore, a green process for obtaining biodegradable MBs is urgently necessary. Aliphatic polyesters, such as poly(lactic acid) (PLA, radiation-degradable) and poly(ε-caprolactone) (PCL, radiation-cross-linkable), have biodegradability and melt processability. The eco-friendly melt electrospraying process is a simple and cost-effective method for the preparation of MBs without the need for organic reagents. In this study, the PLA and PCL MBs were obtained by adjusting the main processing parameters during the melt electrospraying process. The weight losses of PLA and PCL MBs in aqueous environments occurred faster than those of positive controls, and the thermal transition parameters were decreased with the hydrolytic degradation of MBs. In the POP adsorption test, the biodegradable MBs showed poor adsorption because of their low specific surface area. The results of the cleansing efficiency test indicated that biodegradable MBs have great potential as more sustainable cosmetics to replace nondegradable MBs.

Eco-friendly poly(lactic acid) microbeads for cosmetics via melt electrospraying.

Microbeads (MBs) are essential materials for cosmetic and healthcare applications. However, environmental pollution has recently emerged as a concern due to the non-degradability and adsorption property of persistent organic pollutants (POPs) in environmental conditions, particularly in the marine environment. Therefore, the development of biodegradable MBs via eco-friendly methods is urgently demanded. Poly(lactic acid) (PLA) is a biodegradable and melt-processable aliphatic polyester which can be obtained from raw materials in nature. In this study, the high molecular weight PLA was pre-treated by electron beam (E-beam) irradiation in order to adjust the melt viscosity. Subsequently, the PLA MBs were prepared by varying the processing parameters via an eco-friendly melt electrospraying process. During the time, the PLA MBs showed bulk degradation which lead to decrement of the residual weight, thermal and structural stability. On the other hand, the crystallinity of PLA MBs was significantly increased due to the degradation of amorphous region. Furthermore, the PLA MBs showed poor POPs adsorption behavior compare with the commercial MBs because of low specific surface area. From these results, the PLA MBs via green method have a great potential to replace the non-degradable MBs in cosmetics.

Enzymatically Cross-Linked Poly(γ-glutamic acid) Hydrogel with Enhanced Tissue Adhesive Property.

Enzymatic cross-linking of polymer-catechol conjugates in the presence of horseradish peroxidase (HRP) and H2O2 has emerged as an important method to fabricate in situ-forming, injectable hydrogels. Subsequently, tissue adhesion studies using catechol-containing polymers were extensively reported. However, because of the presence of numerous variables such as polymer concentration, oxidizing agent/enzyme, and stoichiometry, the design of the polymer with optimized tissue adhesive property is still challenging. In this study, a poly(γ-glutamic acid) (γ-PGA)-dopamine (PGADA) conjugate was synthesized, and in situ hydrogels were fabricated via enzymatic cross-linking of a catechol moiety. To optimize the tissue adhesive property of the PGADA hydrogel, the effect of various factors, such as polymer concentration, catechol substitution degree (DS), HRP concentration, and H2O2 content, on the gelation behavior and mechanical strength was investigated. The gelation behavior of PGADA hydrogels was characterized using a rheometer and rotational viscometer. Also, the possibility of its use as a tissue adhesive was examined by evaluating the tissue adhesion strength in vitro and ex vivo.

3D Printing of Bone-Mimetic Scaffold Composed of Gelatin/ß-Tri-Calcium Phosphate for Bone Tissue Engineering.

3D printed scaffolds composed of gelatin and ß-tri-calcium phosphate (ß-TCP) as a biomimetic bone material are fabricated, thereby providing an environment appropriate for bone regeneration. The Ca2+ in ß-TCP and COO- in gelatin form a stable electrostatic interaction, and the composite scaffold shows suitable rheological properties for bioprinting. The gelatin/ß-TCP scaffold is crosslinked with glutaraldehyde vapor and unreacted aldehyde groups which can cause toxicity to cells is removed by a glycine washing. The stable binding of the hydrogel is revealed as a result of FTIR and degradation rate. It is confirmed that the composite scaffold has compressive strength similar to that of cancellous bone and 60 wt% ß-TCP groups containing 40 wt% gelatin have good cellular activity with preosteoblasts. Also, in the animal experiments, the gelatin/ß-TCP scaffold confirms to induce bone formation without any inflammatory responses. This study suggests that these fabricated scaffolds can serve as a potential bone substitute for bone regeneration.

Effect of chitin/silk fibroin nanofibrous bicomponent structures on interaction with human epidermal keratinocytes.

To fabricate a biomimetic nanostructured bicomponent scaffolds, two types of chitin/silk fibroin (SF) nanofibrous scaffolds (blend scaffolds and hybrid scaffolds) were prepared by electrospinning or simultaneous electrospinning of chitin/SF solutions. The chitin/SF bicomponent scaffolds were after-treated with water vapor, and their nanofibrous structures were almost maintained. From the cytocompatibility and cell behavior on the chitin/SF blend or hybrid nanofibrous scaffolds, the hybrid matrix with 25% chitin and 75% SF as well as the chitin/SF blend nanofibers could be a potential candidate for tissue engineering scaffolds.

Polyelectrolyte complex nanofibers from poly(γ-glutamic acid) and fluorescent chitosan oligomer.

Polyelectrolyte complex (PEC) nanofibers were fabricated via electrospinning using anionic poly(γ-glutamic acid) (γ-PGA) and cationic fluorescent chitosan oligomer (CHI-O). First, the PEC formation behavior was investigated as a function of the solution concentration, viscosity and blend ratio. The optimum blend ratio and concentration of the anionic γ-PGA and cationic CHI-O for electrospinning was 10/13 (w/w), and continuous nanofibers were obtained at that condition with an average diameter of 370 nm without beads. The resulting PEC nanofibers were chemically crosslinked using glutaraldehyde vapor to provide dimensional stability against water. Confocal microscopy revealed that the fluorescent intensity of the PEC nanofibers increased gradually as the fluorescent CHI-O increased. Also, the fluorescent CHI-O was distributed evenly in the PEC nanofibers through the formation of PEC with anionic γ-PGA. Therefore, the electrospinnability of anionic γ-PGA improved significantly with the PEC formation with cationic CHI-O. This result indicates that anionic biopolymers with a poor electrospinnability can be converted to nanofibers via PEC formation with polycations.

Small diameter vascular graft with fibroblast cells and electrospun poly (L-lactide-co-ε-caprolactone) scaffolds: Cell Matrix Engineering.

Electrospun scaffolds have been widely used in tissue engineering due to their similar structure to native extracellular matrices (ECM). However, one of the obstacles limiting the application of electrospun scaffolds for tissue engineering is the nano-sized pores, which inhibit cell infiltration into the scaffolds. To overcome this limitation, we approached to make layers which are consisted of cells onto the electrospun sheet and then tubular structure was constructed by rolling. We called this as 'Cell Matrix Engineering' because the electrospun sheets were combined with the cells to form one matrix. They maintained 3-D tubular structures well and their diameters were 4.1 mm (±0.1 mm). We compared the mechanical and biological properties of various vascular grafts with the electrospun PLCL sheets of different thickness. In these experiments, the vascular graft made with thin sheets showed a better cell proliferation and attachment than the grafts made with thick sheets because the thin layer allowed for more efficient mass transfer and better permeability than the thick layer. Culturing under physiological pulsatile flow condition was demonstrated in this work. These dynamic conditions provided the improved mass transport and aerobic cell metabolism. Therefore, the Cell Matrix Engineered vascular graft holds a great promise for clinical applications by overcoming the limitations associated with conventional scaffolds.

Injectable methylcellulose hydrogel containing calcium phosphate nanoparticles for bone regeneration.

A novel injectable methylcellulose (MC) hydrogel containing calcium phosphate nanoparticles (CaP NPs) was prepared by an in situ formation process, in which the precursor salts induced a salt-out effect in the MC solution. The thermo-sensitive properties of MC-CaP NPs composite hydrogels with different crystalline phases were characterized by rheometry, infrared spectroscopy and injectability test. The as-prepared MC hydrogels with bioactive CaP NPs had a suitable injectability at the body temperature, irrespective of the crystalline phases of CaP NPs. At the physiological pH condition, the structure of the MC hydrogel containing CaP NPs was analyzed by scanning electron microscopy, X-ray diffraction (XRD). The XRD results indicate that the in situ synthesized CaP NPs had a crystalline phase of hydroxyapatite (HAP). The in vitro study using mesenchymal stem cells showed that MC-HAP NPs composite hydrogel was biocompatible. The in vivo study indicated that the regeneration rate of new mature bone was also higher in the MC-HAP NPs composite hydrogel than in the pure MC hydrogel. The results of this study indicate that injectable MC-HAP NPs composite hydrogel has a great potential for bone tissue regeneration.

Surface modification of PHBV nanofiber mats for rapid cell cultivation and harvesting.

To maintain the original function of a specific tissue for therapeutic tissue engineering, an advanced cell culture surface for repeat cell proliferation is necessary. We designed a novel cell proliferation and rapid harvesting surface by combining nonwoven nanofiber mat and a thermo-responsive polymer. Nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) mats were fabricated by the electrospinning technique. A poly(N-isopropylacrylamide) (PNIPAM) thermo-responsive layer was grafted on the PHBV nanofiber mat by electron beam irradiation. The average diameter of the PNIPAM-grafted PHBV nanofibers was determined by SEM. ATR-FTIR and ESCA were used to confirm the grafting of PNIPAM onto the PHBV nanofiber surface. Water contact angles on the mats were measured in response to temperature changes. Human adipose-derived stem cells (ADSCs) were cultured on the PNIPAM-grafted PHBV nanofiber mat to investigate cell proliferation, harvesting, and functionality during repeat subculture. Detached ADSCs from each surface by low temperature treatment and trypsin-EDTA were compared by a fluorescence-activated cell sorter (FACS) using expression of stem cell membrane-specific markers such as CD-13 PE, CD-29 PE, and CD-90 FITC. The mass cultivation and intact harvesting of stem cells by low temperature treatment using a thermo-responsive PHBV nanofiber mat is a promising technique for use in regenerative medicine and stem cell therapy.

Characteristics of novel monofilament sutures prepared by conjugate spinning.

Compared with braided multifilament sutures, absorbable monofilaments are attractive suture materials as they exhibit less tissue drag and cause less tearing because of their smooth surfaces. However, monofilament sutures are less flexible and more difficult to tie a knot than multifilament ones, and their knots are more likely to loosen due to inferior knot security. Although various approaches have been reported to improve the flexibility of monofilament sutures, they still have limitations regarding poor knot security. To address this problem, we developed a novel technique to fabricate monofilament sutures by a conjugate spinning method, resulting in the formation of a sea/islands type of bicomponent monofilament suture. These sea/islands type bicomponent monofilament sutures, which can place many fine strands of a polymeric fiber within a matrix of another polymer, exhibited excellent knot security, flexibility, and low strain energy, compared with commercially available monofilament sutures.