Designing Multifunctional Devices for Regenerative Pharmacology Based on 3D Scaffolds, Drug-Loaded Nanoparticles, and Thermosensitive Hydrogels: A Proof-of-Concept Study

Abstract

Regenerative pharmacology combines tissue engineering/regenerative medicine (TERM) with drug delivery with the aim to improve the outcomes of traditional TERM approaches. In this work, we aimed to design a multicomponent TERM platform comprising a three-dimensional scaffold, a thermosensitive hydrogel, and drug-loaded nanoparticles. We used a thermally induced phase separation method to obtain scaffolds with anisotropic mechanical properties, suitable for soft tissue engineering. A thermosensitive hydrogel was developed using a Poloxamer® 407-based poly(urethane) to embed curcumin-loaded nanoparticles, obtained by the single emulsion nanoprecipitation method. We found that encapsulated curcumin could retain its antioxidant activity and that embedding nanoparticles within the hydrogel did not affect the hydrogel gelation kinetics nor the possibility to progressively release the drug. The porous scaffold was easily loaded with the hydrogel, resulting in significantly enhanced (4-fold higher) absorption of a model molecule of nutrients (fluorescein isothiocyanate dextran 4kDa) from the surrounding environment compared to pristine scaffold. The developed platform could thus represent a valuable alternative in the treatment of many pathologies affecting soft tissues, by concurrently exploiting the therapeutic effects of drugs, with the 3D framework acting as a physical support for tissue regeneration and the cell-friendly environment represented by the hydrogel.

DataSheet1.PDF

“…At the early time point, the rapid drug release mainly resulted from the drug diffusion since there was no significant hydrogel degradation. Moreover, because of the porous structure of both hydrogels and scaffolds, there was a broad hydrogel-liquid interface (Colucci et al, 2021). Through the diffusion of drugs on the surface, the broad interface was initially mainly responsible for rapid release, which was acceptable in the clinic and consistent with drug delivery patterns in other studies (Katakam et al, 2019;Tundisi et al, 2021).…”

Improvement of mechanical and antibacterial properties of porous nHA scaffolds by fluorinated graphene oxide

“…The porosity ( P ) of the scaffold was measured by the liquid displacement method, 27 using absolute ethanol as the moving fluid into the scaffold pores initial volume of absolute ethanol was recorded as V 1 . The scaffold was placed in the graduated cylinder of absolute ethanol solution and immersed for 5 min.…”

Mesoporous Bioactive Glasses Incorporated into an Injectable Thermosensitive Hydrogel for Sustained Co-Release of Sr2+ Ions and N-Acetylcysteine

“…PEU synthesis was performed through a two-step procedure under N 2 flow, according to our already published protocol (Figure S1) [21,26]. Briefly, 60 g of P407 was first solubilized in 300 mL of anhydrous DCE (20% w/v concentration) in a three-neck round bottom flask under a nitrogen atmosphere.…”