Development of bioadhesive formulations for tissue fixation remains a challenge. The major drawbacks of available bioadhesives are low adhesion strength, toxic byproducts, and complexity of application onto affected tissues. In order to address these problems, this study has developed a hydrogel bioadhesive system based on poly amido amine (PAMAM) dendrimer, grafted (conjugated) with UV-sensitive, 4-[3-(trifluoromethyl)-3H-diazirin-3-yl] benzyl bromide (PAMAM-g-diazirine). This particular diazirine molecule can be grafted to the surface amine groups of PAMAM in a one-pot synthesis. Diazirine functionalities are carbene precursors that form covalent crosslinks with hydrated tissues after low-power UV activation without necessity of free-radical initiators. The rheological properties and adhesion strength to ex vivo tissues are highly controllable depending on diazirine grafting, hydrogel concentration, and UV dose intensity fitting variety types of tissues. Covalent bonds at the tissue/bioadhesive interface provide robust adhesive and mechanical strength in a highly hydrated environment. The free flowing hydrogel conversion to elastic adhesive after UV activation allows intimate contact with the ex vivo swine tissue surfaces with low in vitro cytotoxicity observed, making it a promising bioadhesive formulation toward clinical applications.
Current methods of tissue fixation rely on mechanical-related technologies developed from the clothing and carpentry industries. Herein, a novel bioadhesive method that allows tuneable adhesion and is also applicable to biodegradable polyester substrates is described. Diazirine is the key functional group that allows strong soft tissue crosslinking and on-demand adhesion based on a free radical mechanism. Plasma post-irradiation grafting makes it possible to graft diazirine onto PLGA substrates. When the diazirine-PLGA films, placed on wetted ex vivo swine aortas, are activated with low intensity UV light, lap shear strength of up to 450 ± 50 mN cm(-2) is observed, which is one order of magnitude higher than hydrogel bioadhesives placed on similar soft tissues. The diazirine-modified PLGA thin films could be added on top of previously developed technologies for minimally invasive surgeries. The present work is focused on the chemistry, grafting, and lap shear strength of the alkyl diazirine-modified PLGA bioadhesive films.
The invasive practice of suturing for wound closure has persisted for millennia; with the rate of medical development, it is staggering that there are few viable alternatives to invasive mechanical fasteners. Biocompatible and biodegradable polymers are attractive candidates for versatile bioadhesives and could revolutionize surgical procedures. Bioadhesives can be broadly placed into two groups: activated and instant. Almost all commercially available bioadhesives are instant, which cross-link by mixing two components or on contact with moisture. Activated bioadhesives, on the other hand, allow control of when and where a bioadhesive cross-links and, in some cases, the extent of cross-linking. Despite significant progress, there has been little translation of activated bioadhesives to clinical use. This review discusses recent developments in UV-activated bioadhesives toward addressing unmet clinical needs.
Plasma treatments are investigated as a post-production method of tuning drug release and bioadhesion of poly(lactic-co-glycolic acid) (PLGA) thin films. PLGA films were treated under varying conditions by controlling gas flow rate, composition, treatment time, and radio frequency (RF) power. In vitro release of the drug-like molecule fluorescein diacetate (FDAc) from plasma-treated PLGA was tunable by controlling RF power; an increase of 65% cumulative release is reported compared to controls. Bioadhesion was sensitive to RF power and treatment time, assessed using ex vivo shear-stress tests with wetted swine aorta. We report a maximum bioadhesion ∼6-fold that of controls and 5-fold that of DOPA-based mussel adhesives tested to swine skin.1 The novelty of this post-treatment is the activation of a hydrophobic polyester film for bioadhesion, which can be quenched, while simultaneously tuning drug-release kinetics. This exemplifies the promise of plasma post-treatment for in-clinic bioadhesive activation, along with technological advancements, i.e., atmospheric plasma and hand-held "plasma pencils".
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