Placenta Powder-Infused Thiol-Ene PEG Hydrogels as Potential Tissue Engineering Scaffolds.

Human placenta is a source of extracellular matrix for tissue engineering. In this study, placenta powder (PP), made from decellularized human placenta, was physically incorporated into synthetic poly(ethylene glycol) (PEG)-based hydrogels via UV-initiated thiol-ene coupling (TEC). The PP-incorporated PEG hydrogels (MoDPEG+) showed tunable storage moduli ranging from 1080 ± 290 to 51,400 ± 200 Pa. The addition of PP (1, 4, or 8 wt %) within the PEG hydrogels increased the storage moduli, with the 8 wt % PP hydrogels showing the highest storage moduli. PP reduced the swelling ratios compared with the pristine hydrogels (MoDPEG). All hydrogels showed good biocompatibility in vitro toward human skin cells and murine macrophages, with cell viability above 91%. Importantly, cells could adhere and proliferate on MoDPEG+ hydrogels due to the bioactive PP, while MoDPEG hydrogels were bio-inert as cells moved away from the hydrogel or were distributed in a large cluster on the hydrogel surface. To showcase their potential use in application-driven research, the MoDPEG+ hydrogels were straightforwardly (i) 3D printed using the SLA technique and (ii) produced via high-energy visible light (HEV-TEC) to populate damaged soft-tissue or bone cavities. Taking advantage of the bioactivity of PP and the tunable physicochemical properties of the synthetic PEG hydrogels, the presented MoDPEG+ hydrogels show great promise for tissue regeneration.

Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections.

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.