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Hydroxyl radical (•OH) is a potent reactive oxygen species with the ability to degrade hazardous organic compounds, kill bacteria, and inactivate viruses. However, an off-the-shelf, portable, and easily activated biomaterial for generating •OH does not exist. Here, microgels were functionalized with catechol, an adhesive moiety found in mussel adhesive proteins, and hematin (HEM), a hydroxylated Fe3+ion-containing porphyrin derivative. When the microgel was hydrated in an aqueous solution with physiological pH, molecular oxygen in the solution oxidized catechol to generate H2O2, which was further converted to •OH by HEM. The generated •OH was able to degrade organic dyes, including orange II and malachite green. Additionally, the generated •OH was antimicrobial against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus epidermidis) bacteria with the initial concentration of 106to 107cfu/mL. These microgels also reduced the infectivity of a nonenveloped porcine parvovirus and an enveloped bovine viral diarrhea virus by 3.5 and 4.5 log reduction values, respectively (99.97–99.997% reduction in infectivity). These microgels were also functionalized with positively charged [2-(methacryloyloxy)ethyl] trimethylammonium chloride, which significantly enhanced the antibacterial and antiviral activities through electrostatic interaction between the negatively charged pathogens and the microgel. These microgels can potentially serve as a lightweight and portable source of disinfectant for an on-demand generation of •OH with a wide range of applications.

Catechol-based bioadhesives generate hydrogen peroxide (H2O2) as a byproduct during the curing process. H2O2can have both beneficial and deleterious effects on biological systems depending on its concentration. To control the amount of H2O2released from catechol-containing polyethylene glycol-based adhesive (PEG-DA), an adhesive was formulated with silica nanoparticles (SiNPs) prepared with increased porosity and acid treatment to increase Si–OH surface content. These SiNPs demonstrated increased surface area, which promoted interaction with catechol and resulted in an increased cure rate, bulk mechanical properties, and adhesive properties of PEG-DA. Most importantly, the SiNPs demonstrated a 50% reduction in the released H2O2while improving the cell viability and proliferation of three primary cell types, including rat dermal fibroblasts, human epidermal keratinocytes, and human tenocytes. Additionally, the SiNPs degraded into soluble Si, which also contributed to increased cell proliferation. Incorporation of porous and acid-treated SiNPs can be a useful approach to simultaneously modulate the concentration of H2O2while increasing the adhesive performance of catechol-based adhesives.

Fibrin microparticles were incorporated into poly(ethylene) glycol (PEG)-fibrinogen hydrogels to create an injectable composite that could serve as a wound healing support and vehicle to deliver therapeutic factors for tissue engineering. Nitric oxide (NO), a therapeutic agent in wound healing, was loaded into fibrin microparticles by blending S-nitroso-N-acetyl penicillamine (SNAP) with a fibrinogen solution. The incorporation of microparticles affected swelling behavior and improved tissue adhesivity of composite hydrogels. Controlled NO release was induced via photolytic and thermal activation, and modulated by weight percent of particles incorporated. These NO-releasing composites were noncytotoxic in culture. Cells maintained morphology, viability, and proliferative character. Fibrin microparticles loaded with SNAP and incorporated into a PEG-fibrinogen matrix creates a novel injectable composite hydrogel that offers improved tissue adhesivity and inducible NO-release for use as a regenerative support for wound healing and tissue engineering applications.

A series of unconventional approaches has been developed at Michigan Technological University, which is able to screen candidate materials for use in bioabsorbable (or bioresorbable) stents by reducing the scale of necessary animal studies and the complexity of biocorrosion analyses. Using a novel in vivo approach, materials formed into a simplified wire geometry were implanted into the wall of the abdominal aorta of rodents for several weeks or months to measure the extent of in vivo degradation, quantify mechanical strength over time, characterize the resulting products, and assess biocompatibility. An in vitro method was developed to identify bioabsorbable candidate materials, reproduce the corrosion products formed in vivo, and predict the degradation rate of stent materials. To accomplish this goal, wires were encapsulated in an extracellular matrix and corroded in cell culture media in vitro. Encapsulation of the wires in vitro was necessary in order to mimic in vivo stent encapsulation within a neo-intima. Alternatively, accelerated in vitro corrosion for materials with very low corrosion rates was accomplished by exposing fibrin-coated wires to a steady flow of cell culture media. After in vivo and in vitro tests, wires were subjected to tensile testing to quantify the rate of material degradation and loss of mechanical strength.

An S-nitroso-N-acetylpenicillamine (SNAP) derivatization approach was used to modify existing free primary amines found in fibrin (a natural protein-based biomaterial) to generate a controlled nitric oxide (NO) releasing scaffold material. The duration of the derivatization reaction affects the NO release kinetics, the induction of controlled NO-release, hydrophobicity, swelling behavior, elastic moduli, rheometric character, and degradation behavior. These properties were quantified to determine changes in fibrin hydrogels following covalent attachment of SNAP. NO-releasing materials exhibited minimal cytotoxicity when cultured with fibroblasts or osteoblasts. Cells maintained viability and proliferative character on derivatized materials as demonstrated by Live/Dead cell staining and counting. In addition, SNAP-derivatized hydrogels exhibited an antimicrobial character indicative of NO-releasing materials. SNAP derivatization of natural polymeric biomaterials containing free primary amines offers a means to generate inducible NO-releasing biomaterials for use as an antimicrobial and regenerative support for tissue engineering.

Currently available biomedical adhesives are mainly engineered to have one function (i.e., providing mechanical support for the repaired tissue). To improve the performance of existing bioadhesives and broaden their applications in medicine, numerous multifunctional bioadhesives are reported in the literature. These adhesives can be categorized as passive or active by design. Passive multifunctional bioadhesives contain inherent compositions and structural designs that can carry out additional functions without added external influences. These adhesives exhibit new functionalities such as antimicrobial properties, self‐healing abilities, the ability to promote cellular ingrowth, and the ability to be reshaped. Conversely, active multifunctional bioadhesives respond to environmental changes (e.g., pH, temperature, electricity, light, and biomolecule concentration), which initiate a change in the adhesive to release encapsulated drugs or to activate or deactivate the bioadhesive for interfacial binding. This review article highlights recent advances in multifunctional bioadhesives. This reviewdiscusses strategies for engineering multifunctional biomedical adhesives, which involve two general approaches: passive and active design. Passive adhesives contain inherent structural elements that can carry out additional functions without external influences, whereas active adhesives are designed to respond to environmental changes. These adhesives exhibit new functionality such as antimicrobial properties, self‐healing ability, and the capacity to release drugs.