Surface modification of biomaterials, particularly by adding bioactive coatings, enhances cell-material interactions at the nanoscale, improving implant performance at the macroscale. One approach involves gene delivery via surface-bound coatings, allowing for controlled local release of viral particles. However, viral gene delivery systems, such as lentiviral vectors, face challenges in precision targeting and transduction efficiency. To address these, a bio-orthogonal coating was developed and used on titanium using chemical vapor deposition (CVD) polymerization. Co-presenting a cell binding peptide and immobilized lentiviral particles on the surface of Ti increased gene delivery efficiency by directing cells to the surface, making them easier to transduce. Specifically, a poly[(4-(3,4dibromomaleimide)-p-xylylene)-co-(4-pentafluorophenol ester-p-xylylene)] coating was prepared using CVD polymerization on Ti discs as a bio-orthogonal layer to tether lentiviral particles delivering GJA1, the gene for the gap junction protein Connexin 43 (Cx43) and the mesenchymal stem cell (MSC) binding peptide, DPIYALSWSGMA. The polymer coating exhibited high binding efficiency for both lentivirus and peptide, allowing for precise microcontact printing. Immobilized lentiviral transduction efficiency matched that in supernatant, with co-delivery increasing transduction efficiency by 35%. The biorthogonal coating boosted MSC binding 2.7-fold, leading to a density-dependent rise in cell–cell communication. High-density seeding enabled gap junction formation, while Cx43 transduction increased intercellular communication by 36%. In low-density culture, transduction led to an 84% increase in cell–cell communication within 4 h of in vitro culture. This work presents a simple, repeatable surface modification method for biomolecular immobilization, combining engineered viral vectors and peptides to enhance gene delivery approaches.

Bone plays critical roles in support, protection, movement, and metabolism. Although bone has an innate capacity for regeneration, this capacity is limited, and many bone injuries and diseases require intervention. Biomaterials are a critical component of many treatments to restore bone function and include non-resorbable implants to augment bone and resorbable materials to guide regeneration. Biomaterials can vary considerably in their biocompatibility and bioactivity, which are functions of specific material parameters. The success of biomaterials in bone augmentation and regeneration is based on their effects on the function of bone cells. Such functions include adhesion, migration, inflammation, proliferation, communication, differentiation, resorption, and vascularization. This review will focus on how different material parameters can enhance bone cell function both in vitro and in vivo.

Biomaterial strategies focused on designing scaffolds with physiologically relevant gradients provide a promising means for elucidating 3D vascular cell responses to spatial and temporal variations in matrix properties. In this study, we present a photopolymerization approach, ascending photofrontal free-radical polymerization, to generate proteolytically degradable hydrogel scaffolds of poly(ethylene) glycol with tunable continuous gradients of (1) elastic modulus (slope of 80 Pa/mm) and uniform immobilized RGD concentration (2.06 ± 0.12 mM) and (2) immobilized concentration of the RGD cell-adhesion peptide ligand (slope of 58.8 μM/mm) and uniform elastic modulus (597 ± 22 Pa). Using a coculture model of vascular sprouting, scaffolds embedded with gradients of elastic modulus induced increases in the number of vascular sprouts in the opposing gradient direction, whereas RGD gradient scaffolds promoted increases in the length of vascular sprouts toward the gradient. Furthermore, increases in vascular sprout length were found to be prominent in regions containing higher immobilized RGD concentration.