Pseudopeptides containing the d-Oxd or the d-pGlu [Oxd = (4R,5S)-4-methyl-5-carboxyl-oxazolidin-2-one, pGlu = pyroglutamic acid] moiety and selected amino acids were used as low-molecular-weight gelators to prepare strong and thixotropic hydrogels at physiological pH. The addition of calcium chloride to the gelator solutions induces the formation of insoluble salts that get organized in fibers at a pH close to the physiological one. Physical characterization of hydrogels was carried out by morphologic evaluation and rheological measurements and demonstrated that the analyzed hydrogels are thixotropic, as they have the capability to recover their gel-like behavior. As these hydrogels are easily injectable and may be used for regenerative medicine, they were biologically assessed by cell seeding and viability tests. Human gingival fibroblasts were embedded in 2% hydrogels; all of the hydrogels allow the growth of encapsulated cells with a very good viability. The gelator toxicity may be correlated with their tendency to self-assemble and is totally absent when the hydrogel is formed.

Intracranial delivery of therapeutic agents is limited by penetration beyond the blood-brain barrier (BBB) and rapid metabolism of the drugs that are delivered. Convection-enhanced delivery (CED) of drug-loaded nanoparticles (NPs) provides for local administration, control of distribution, and sustained drug release. While some investigators have shown that repeated CED procedures are possible, longer periods of sustained release could eliminate the need for repeated infusions, which would enhance safety and translatability of the approach. Here, we demonstrate that nanoparticles formed from poly(ethylene glycol)-poly(ω-pentadecalactone-co-p-dioxanone) block copolymers [PEG-poly(PDL-co-DO)] are highly efficient nanocarriers that provide long-term release: small nanoparticles (less than 100 nm in diameter) continuously released a radiosensitizer (VE822) over a period of several weeks in vitro, provided widespread intracranial drug distribution during CED, and yielded significant drug retention within the brain for over 1 week. One advantage of PEG-poly(PDL-co-DO) nanoparticles is that hydrophobicity can be tuned by adjusting the ratio of hydrophobic PDL to hydrophilic DO monomers, thus making it possible to achieve a wide range of drug release rates and drug distribution profiles. When administered by CED to rats with intracranial RG2 tumors, and combined with a 5-day course of fractionated radiation therapy, VE822-loaded PEG-poly(PDL-co-DO) NPs significantly prolonged survival when compared to free VE822. Thus, PEG-poly(PDL-co-DO) NPs represent a new type of versatile nanocarrier system with potential for sustained intracranial delivery of therapeutic agents to treat brain tumors.

Nonwoven fibrous mats based on semicrystalline networks are prepared starting from poly(ε-caprolactone) and properly combining electrospinning and sol-gel reactions. The mats are obtained as continuous, randomly oriented micrometric fibers with different network densities. The systems are subjected to thermomechanical cycles to investigate their one-way and two-way shape memory behavior. One-way tests aim at exploring the effects of the deformation temperature on the materials response, with particular interest to the less investigated cold-working conditions (i.e., deformation temperature below T m ). The materials display two-way shape memory capabilities (i.e., the ability to change between two distinguished shapes upon heating and cooling under a fixed nonzero stress) and the effect of the applied stress is explored. The shape memory characterization is accompanied by an ex situ SEM analysis, to describe the concurrent microstructural evolution during the macroscopic shape variation, and by the assessment of their biocompatibility, to explore the suitability of the nonwovens for biomedical applications.

Regulating stem cell adhesion and growth onto functionalized biomaterial scaffolds is an important issue in the field of tissue engineering and regenerative medicine. In this study, new electrospun scaffolds of poly( l -lactic acid) (PLLA), as bioresorbable polymer, and β-lactam compounds agonists of selected integrins, as functional components with cell adhesive properties, are designed. The new β-lactam-PLLA scaffolds contribute significantly in guiding protein translation involved in human bone marrow mesenchymal stem cells (hBM-MSC) adhesion and integrin gene expression. Scanning electron microscopy, confocal laser scanning microscopy, and Western Blot analyses reveal that GM18-PLLA shows the best results, promoting cell adhesion by significantly driving changes in focal adhesion proteins distribution (β 1 integrin and vinculin) and activation (pFAK), with a notable increase of GM18-targets subunits integrin gene expression, α 4 and β 1 . These novel functionalized submicrometric fibrous scaffolds demonstrate, for the first time, the powerful combination of selective β-lactams agonists of integrins with biomimetic scaffolds, suggesting a designed rule that could be suitably applied to tissue repair and regeneration.

A smart combination of electrospinning and sol–gel reaction enabled to develop crosslinked poly(ε-caprolactone) fibrous mats showing excellent shape memory properties.