RESUMO
Hydroxyapatite (HA) infused triazine-trione (TATO) composites have emerged as an injectable platform for customizable bone fixators due to their fast and benign curing via high-energy visible light-induced thiol-ene chemistry (HEV-TEC), promising mechanical performance, and preclinical outcomes. These composites can overcome many of the existing limitations accompanying metal implants such as poor patient customizability, soft tissue adhesions, and stress shielding. Taking into account that the promising benchmarked TATO composite (BC) is based on stable sulfur-carbon bonds, we herein investigate the impact of introducing polyester dendritic cross-linkers based on bis-MPA as chemically integrated branched additives that display labile esters in a branched configuration. The inclusion of dendrimers, G1 and G3, in concentrations of 1, 3, and 5 wt % in the composite formulations were found to (i) decrease the processing viscosity of the composite formulations, reaching Newtonic and nonshear thinning behavior at 37 °C and (ii) impact the size distribution of bubble cavities in the composite cross sections. The lowest collected Tg for the dendrimer-containing composites was noted to be 73.2 °C, a temperature well above physiological temperature. Additionally, all composites displayed flexural modulus above 6 GPa and flexural strength of ca. 50 MPa under dry conditions. The composites comprising 5 wt % of G1 and G3 dendrimers, with ester bond densities of 0.208 and 0.297 mmol/g, respectively, reached a mass loss up to 0.27% in phosphate buffered saline at 37 °C, which is within the range of established polycaprolactone (PCL). Combined with the nontoxic properties extracted from the cell viability study, polyester dendrimers were determined as promising additives which compatibilized well with the TATO formulation and cross-linked efficiently resulting in strong composites suited for bone fracture fixations.
RESUMO
Antimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK-060, a human kininogen-derived AMP. Once embedded into the poloxamer gel, DPK-060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time-kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti-infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK-060 at the wound site, all formulations display superior efficacy compared to DPK-060 in solution.
