Characterization of Tunable FGF-2 Releasing Polyelectrolyte Multilayers

Abstract

Fibroblast growth factor 2 (FGF-2) is a potent mediator of stem cell differentiation and proliferation. Although FGF-2 has a well-established role in promoting bone tissue formation, flaws in its delivery have limited its clinical utility. Polyelectrolyte multilayer films represent a novel system for FGF-2 delivery that has promise for local, precisely controlled and sustained release of FGF-2 from surfaces of interest including medical implants and tissue engineering scaffolds. In this work, the loading and release of FGF-2 from synthetic hydrolytically degradable multilayer thin films of various architectures is explored; drug loading was tunable using at least three parameters (number of nanolayers, counterpolyanion, and type of degradable polycation) and yielded values of 7-45 ng/cm2 of FGF-2. Release time varied between 24 hours and approximately five days. FGF-2 released from these films retained in vitro activity, promoting the proliferation of MC3T3 pre-osteoblast cells. The use of biologically derived counterpolyanions heparin sulfate and chondroitin sulfate in the multilayer structures enhanced FGF-2 activity. The control over drug loading and release kinetics inform future in vivo bone and tissue regeneration models for the exploration of clinical relevance of LbL growth factor delivery films.

Polyelectrolyte Multilayers in Tissue Engineering

“…91,92 The release of fibroblast growth factor 2 (FGF-2) has been controlled with the construction of poly (b-aminoester)s/heparin (HEP)/FGF-2/HEP tetralayers deposited on top of PEI/SPS multilayers. 43 This approach was similar to another study using tetralayers for controlled hydrophobic drug and polysaccharide release. 93 The incorporation of the poly (b-aminoester) polymer into the tetramer was to prevent the localized degradation of the PEM due to cellular interactions.…”

“…The bioactivity of the released protein was verified through its exposure to preosteoblasts and by monitoring their proliferation. 43 Information on additional studies investigating the delivery of bioactive molecules using PEMs is provided in Table 2, further supporting the versatility of PEMs in stimulating phenotypic maintenance.…”

“…42 Largely due to their tunable nature, PEMs have had a significant impact in nearly every aspect of biomaterial design and tissue engineering. 10,18,22,24,26,27,30,31,38,[42][43][44][45][46][47][48][49][50][51][52][53][54][55] PEMs have been used to modulate protein adsorption, 33 promote cell adhesion, 16,29,34,38,[55][56][57] or regulate the inflammatory response. [58][59][60] In addition, PEM coatings have the potential to mimic the complex extracellular matrix found in vivo.…”

Immunomodulation with Self-Crosslinked Polyelectrolyte Multilayer-Based Coatings

“…34 The obtained multilayers are widely used as controlled-release drug systems without changing their biological function within the coating. [35][36][37][38] Sukhishvili et al have recently reported a coating with a "self-defense" behavior that promotes the release of different dose of antibiotic in function of the decrease of the pH around the surface due to the presence of bacteria. 39 Here, we report, for the first time, polyelectrolyte multilayers films made of poly-(Llysine) and hyaluroanan-aldehyde (PLL/HA-Ald) derivative, which possess the main advantage to form stable structures through an auto-crosslinking mechanism.…”

The characterization of protein release from sericin film in the presence of an enzyme: Towards fibroblast growth factor-2 delivery

“…Cell culture medium consisting of alpha minimum essential medium (␣MEM, Invitrogen, Carlsbad, CA, USA) supplemented with 1% albumin and 1% penicillin/streptomycin based on the method of Macdonald et al (2010) was used as the test medium. One hundred microliters of the cell culture medium was added to each well with a cast SC film containing FGF-2 (2500, 250, or 25 ng/unit) and incubated at 37 • C. The medium was replaced daily with 100 l of flesh medium.…”