Publications

Percutaneous medical devices - such as prosthetic limbs, dental implants, and subgingival dental restorations commonly fail due to their susceptibility to infection, posing serious morbidity and mortality and a significant economic burden. Current solutions for subgingival dental restoration failure - such as antimicrobial and degradation-resistant materials - remain largely experimental and have yet to achieve widespread clinical translation. Thus, as a next-generation strategy for improving subgingival restoration longevity, we draw inspiration from the tooth, a long-lasting percutaneous organ with robust soft tissue attachment enabled by cellmatrix adhesive hemidesmosomes (HDs). Promoting HD formation around subgingival restorations - mimicking the natural attachment seen in teeth - may extend dental restoration lifespan by fostering a stable mucosal barrier that blocks bacterial access. A family of scalable biologics-free HD instructive light-curable biosealants (HILBs) was engineered for point-of-care coating for subgingival restorations to trigger and guide beneficial pericellular extracellular matrix structural changes at the HILB surface. Material-based strategies for medical device integration with the human body have traditionally focused on controlling surface properties to provoke desired cellular and tissue responses at the bio/non-bio interface. However, this approach overlooks the evolving pericellular matrix that quickly enrobes cells and overrides engineered surface cues. The control of cell-secreted nascent matrix through HILB surface polarity markedly upregulated HD formation. This bioinstruction is dependent on nascent glycoprotein laminin332 secretion and recognized by HD integrins, which demonstrates the potential of biomaterial surface design to guide secreted pericellular matrix with implications for facilitating tissue repair and enhancing subgingival restoration outcomes.

JTD Keywords: Binding, Bioinspiration, Bioinstructive polar surface, Cells, Expression, Hemidesmosomes, Human keratinocytes, Ionomer, Keratinocytes adhesion, Laminin-5 gamma-2 chain, Light-curable biomaterial, Metalloproteinases, Proteins, Self-etch adhesives, Surface-energy

Unlike the attachment of soft epithelial skin tissue to penetrating solid natural structures like fingernails and teeth, sealing around percutaneous/permucosal devices such as dental implants is hindered by inflammation and epidermal down growth. Here, we employed a dual keratinocyte-adhesive peptide and anti-inflammatory biomolecule coating on titanium to promote oral epithelial tissue attachment. For minimizing inflammation-triggered epidermal down growth, we coated pristine and oxygen plasma pre-treated polished titanium (pTi) with conjugated linoleic acid (CLA). Further, in order to aid in soft tissue attachment via the formation of hemidesmosomes, adhesive structures by oral keratinocytes, we coated the anionic linoleic acid (LA) adsorbed titanium with cationic cell adhesive peptides (CAP), LamLG3, a peptide derived from Laminin 332, the major extracellular matrix component of the basement membrane in skin tissue and Net1, derived from Netrin-1, a neural chemoattractant capable of epithelial cell attachment via alpha 6 beta 4 integrins. The dual CLA-CAP coatings on pTi were characterized by X-ray photoelectron spectroscopy and dynamic water contact angle measurements. The proliferation of human oral keratinocytes (TERT-2/OKF6) was accelerated on the peptide coated titanium while also promoting the expression of Col XVII and beta-4 integrin, two markers for hemidesmosomes. Simultaneously, CLA coating suppressed the production of inducible nitric oxide synthase (anti-iNOS); a pro-inflammatory M1 marker expressed in lipopolysaccharide (LPS) stimulated murine macrophages (RAW 264.7) and elevated expression of anti-CD206, associated to an anti-inflammatory M2 macrophage phenotype. Taken together, the dual keratinocyte-adhesive peptide and anti-inflammatory biomolecule coating on titanium can help reduce inflammation and promote permucosal/peri-implant soft tissue sealing.

JTD Keywords: Adhesives, Animal, Animals, Anti-inflammatories, Anti-inflammatory agents, Antiinflammatory agent, Biomolecules, Bone, Cell adhesion, Cell-adhesives, Coatings, Conjugated linoleic acid, Conjugated linoleic-acid, Contact angle, Hemidesmosome, Hemidesmosomes, Human, Humans, Hydroxyapatite, Inflammation, Integrins, Keratinocyte, Keratinocytes, Linoleic acid, Macrophages, Mice, Mouse, Nitric oxide, Oral implants, Pathology, Peptides, Skin tissue, Soft tissue, Supplementation, Surface properties, Surface property, Tissue, Titania, Titanium, X ray photoelectron spectroscopy

Resveratrol and gallic acid were co-loaded in phospholipid vesicles aiming at protecting the skin from external injuries, such as oxidative stress and microbial infections. Liposomes were prepared using biocompatible phospholipids dispersed in water. To improve vesicle stability and applicability, the phospholipids and the phenols were dispersed in water/propylene glycol or water/glycerol, thus obtaining PEVs and glycerosomes, respectively. The vesicles were characterized by size, morphology, physical stability, and their therapeutic efficacy was investigated in vitro. The vesicles were spherical, unilamellar and small in size: liposomes and glycerosomes were around 70 nm in diameter, while PEVs were larger (∼170 nm). The presence of propylene glycol or glycerol increased the viscosity of the vesicle systems, positively affecting their stability. The ability of the vesicles to promote the accumulation of the phenols (especially gallic acid) in the skin was demonstrated, as well as their low toxicity and great ability to protect keratinocytes and fibroblasts from oxidative damage. Additionally, an improvement of the antimicrobial activity of the phenols was shown against different skin pathogens. The co-loading of resveratrol and gallic acid in modified phospholipid vesicles represents an innovative, bifunctional tool for preventing and treating skin affections.

JTD Keywords: Fibroblasts, Keratinocytes, Phenol, Phospholipid vesicle, Skin pathogens