Development of tannin-inspired antimicrobial bioadhesives.

Tissue adhesives play an important role in surgery to close wounds, seal tissues, and stop bleeding, but existing adhesives are costly, cytotoxic, or bond weakly to tissue. Inspired by the water-resistant adhesion of plant-derived tannins, we herein report a new family of bioadhesives derived from a facile, one-step Michael addition of tannic acid and gelatin under oxidizing conditions and crosslinked by silver nitrate. The oxidized polyphenol groups of tannic acid enable wet tissue adhesion through catecholamine-like chemistry, while both tannic acid and silver nanoparticles reduced from silver nitrate provide antimicrobial sources inherent within the polymeric network. These tannin-inspired gelatin bioadhesives are low-cost and readily scalable and eliminate the concerns of potential neurological effect brought by mussel-inspired strategy due to the inclusion of dopamine; variations in gelatin source (fish, bovine, or porcine) and tannic acid feeding ratios resulted in tunable gelation times (36 s-8 min), controllable degradation (up to 100% degradation within a month), considerable wet tissue adhesion strengths (up to 3.7 times to that of fibrin glue), excellent cytocompatibility, as well as antibacterial and antifungal properties. The innate properties of tannic acid as a natural phenolic crosslinker, molecular glue, and antimicrobial agent warrant a unique and significant approach to bioadhesive design. STATEMENT OF SIGNIFICANCE: This manuscript describes the development of a new family of tannin-inspired antimicrobial bioadhesives derived from a facile, one-step Michael addition of tannic acid and gelatin under oxidizing conditions and crosslinked by silver nitrate. Our strategy is new and can be easily extended to other polymer systems, low-cost and readily scalable, and eliminate the concerns of potential neurological effect brought by mussel-inspired strategy due to the inclusion of dopamine. The tannin-inspired gelatin bioadhesives hold great promise for a number of applications in wound closure, tissue sealant, hemostasis, antimicrobial and cell/drug delivery, and would be interested to the readers from biomaterials, tissue engineering, and drug delivery area.

Design strategies and applications of nacre-based biomaterials.

The field of tissue engineering and regenerative medicine relies heavily on materials capable of implantation without significant foreign body reactions and with the ability to promote tissue differentiation and regeneration. The field of bone tissue engineering in particular requires materials capable of providing enhanced mechanical properties and promoting osteogenic cell lineage commitment. While bone repair has long relied almost exclusively on inorganic, calcium phosphate ceramics such as hydroxyapatite and their composites or on non-degradable metals, the organically derived shell and pearl nacre generated by mollusks has emerged as a promising alternative. Nacre is a naturally occurring composite material composed of inorganic, calcium carbonate plates connected by a framework of organic molecules. Similar to mammalian bone, the highly organized microstructure of nacre endows the composite with superior mechanical properties while the organic phase contributes to significant bioactivity. Studies, both in vitro and in vivo, have demonstrated nacre's biocompatibility, biodegradability, and osteogenic potential, which are superior to pure inorganic minerals such as hydroxyapatite or non-degradable metals. Nacre can be used directly as a bulk implant or as part of a composite material when combined with polymers or other ceramics. While nacre has demonstrated its effectiveness in multiple cell culture and animal models, it remains a relatively underexplored biomaterial. This review introduces the formation, structure, and characteristics of nacre, and discusses the present and future uses of this biologically-derived material as a novel biomaterial for orthopedic and other tissue engineering applications. STATEMENT OF SIGNIFICANCE: Mussel derived nacre, a biological composite composed of mineralized calcium carbonate platelets and interplatelet protein components, has recently gained interest as a potential alternative ceramic material in orthopedic biomaterials, combining the integration and mechanical capabilities of calcium phosphates with increased bioactivity derived from proteins and biomolecules; however, there is limited awareness of this material's potential. Herein, we present, to our knowledge, the first comprehensive review of nacre as a biomaterial. Nacre is a highly promising yet overlooked biomaterial for orthopedic tissue engineering with great potential in a wide variety of material systems. It is our hope that publication of this article will lead to increased community awareness of the potential of nacre as a versatile, bioactive ceramic capable of improving bone tissue regeneration and will elicit increased research effort and innovation utilizing nacre.

[Isolation, purification of collagen from soft-shelled turtle calipash for application in biomaterial].

Recently, research on collagen attracts more interests due to its good biological compatibility. The present study attempted to establish a fast and efficient method to purify collagen from soft-shelled turtle and to explore its application in biological materials. The structure and type of collagen fiber in calipash were determined by van Gieson staining and Picrosirius red staining, which could contribute to the isolation of collagen from soft-shelled turtle Calipash (STCC). Collagen fibers were in high content and the main collagen fiber was type I in STCC. The crude STCC solution was purified by dialysis with different cut-off molecular weight. SDS-PAGE demonstrated that the best purification was in applying 100 kDa dialysis bags after 48 h. The water absorbing capacity and holding capacity of STCC were up to 12.06 g/g and 98.21%, respectively. STCC can be degraded by collagenase in vitro entirely after 72 h. The hemolysis, skin sensitization, hemostatic and wound healing of STCC were determined by using SD rat model, and the collagen cross-linked by glutaric dialdehyde was set as a comparison. STCC and STCC cross-linked did not result in destructed red blood cell, inflamed and sensitized skin. Both materials exhibited good hemostatic effect. Thus, STCC improved the wound healing efficiently. This study implies a potential of STCC in the field of biomaterial.

Purification, optimization and physicochemical properties of collagen from soft-shelled turtle calipash.

The present work was to optimize the purification conditions for soft-shelled turtle (Pelodiscus sinensis) calipash collagen (STCC) isolated by pepsin and to explore collagen physicochemical properties for potential biomaterial applications. Single-factor test and orthogonal method L9 (3(4)) were employed with the STCC recovery yield as indicator. The optimum purification conditions were obtained when NaCl concentration, collagen concentration and purification time were 2M, 8g/L, and 24h, respectively. Purified STCC were characterized by SDS-PAGE, UV scanning, FTIR, solubility, thermal behavior and amino acid analysis. The results showed that STCC contained high hydroxyproline content than that of other fishery skins, belonging to typical type I collagen in form of [α1(I)] 2α2(I). FTIR spectra of STCC were quite similar to other aquatic animals' collagens. It has the lowest solubility at pH 6, and when NaCl concentration decreased from 2% to 6% (w/v), solubility dropped. The denaturation temperature (Td) and melting temperature (Tm) were 35.1°C and 105.14°C, respectively. Morphology of STCC depicted as regular and porous network structure by SEM. In general, the results suggested that turtle calipash can be exploited as alternatives to mammalian collagen and could also be used for biomedical applications as a potential new material.

Fluorescence imaging enabled poly(lactide-co-glycolide).

Fluorescent biomaterials have attracted significant research efforts in the past decades. Herein, we report a new series of biodegradable, fluorescence imaging-enabled copolymers, biodegradable photoluminescent poly(lactide-co-glycolide) (BPLP-co-PLGA). Photoluminescence characterization shows that BPLP-co-PLGA solutions, films and nanoparticles all exhibit strong, tunable and stable photoluminescence. By adjusting the molar ratios of L-lactide (LA)/glycolide (GA) and (LA+GA)/BPLP, full degradation of BPLP-co-PLGA can be achieved in 8-16 weeks. The fluorescence decay behavior of BPLP-co-PLGA can be used for non-invasive monitoring of material degradation. In vitro cytotoxicity and in vivo foreign body response evaluations demonstrate that BPLP-co-PLGA exhibits similar biocompatibility to poly(lactide-co-glycolide) (PLGA). The imaging-enabled BPLP-co-PLGA was fabricated into porous scaffolds whose degradation can be monitored through non-invasive imaging and nanoparticles that show theranostic potential demonstrated by fluorescent cellular labeling, imaging and sustained 5-fluorouracil delivery. The development of inherently fluorescent PLGA copolymers is expected to impact the use of already widely accepted PLGA polymers for applications where fluorescent properties are highly desired but limited by the conventional use of cytotoxic quantum dots and photobleaching organic dyes. STATEMENT OF SIGNIFICANCE: This manuscript describes a novel strategy of conferring intrinsic photoluminescence to the widely used biodegradable polymers, poly(lactide-co-glycolide) without introducing any cytotoxic quantum dots or photo-bleaching organic dyes, which may greatly expand the applications of these polymers in where fluorescent properties are highly desired. Given the already significant impact generated by the use of PLGA and alike, this work contributes to fluorescence chemistry and new functional biomaterial design and will potentially generate significant impact on many fields of applications such as tissue engineering, molecular imaging and labeling, and drug delivery.

Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives.

Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern.

Design of antimicrobial peptides conjugated biodegradable citric acid derived hydrogels for wound healing.

Wound healing is usually facilitated by the use of a wound dressing that can be easily applied to cover the wound bed, maintain moisture, and avoid bacterial infection. In order to meet all of these requirements, we developed an in situ forming biodegradable hydrogel (iFBH) system composed of a newly developed combination of biodegradable poly(ethylene glycol) maleate citrate (PEGMC) and poly(ethylene glycol) diacrylate (PEGDA). The in situ forming hydrogel systems are able to conform to the wound shape in order to cover the wound completely and prevent bacterial invasion. A 2(k) factorial analysis was performed to examine the effects of polymer composition on specific properties, including the curing time, Young's modulus, swelling ratio, and degradation rate. An optimized iFBH formulation was achieved from the systematic factorial analysis. Further, in vitro biocompatibility studies using adult human dermal fibroblasts (HDFs) confirmed that the hydrogels and degradation products are not cytotoxic. The iFBH wound dressing was conjugated and functionalized with antimicrobial peptides as well. Evaluation against bacteria both in vitro and in vivo in rats demonstrated that the peptide-incorporated iFBH wound dressing offered excellent bacteria inhibition and promoted wound healing. These studies indicated that our in situ forming antimicrobial biodegradable hydrogel system is a promising candidate for wound treatment.