Analysis of early cellular responses of anterior cruciate ligament fibroblasts seeded on different molecular weight polycaprolactone films functionalized by a bioactive poly(sodium styrene sulfonate) polymer

Abstract

With the growing number of anterior cruciate ligament (ACL) ruptures and the increased interest for regenerative medicine procedures, many researches concentrate on developing bioactive and biodegradable synthetic ligaments. In this regard, the choice of raw material with appropriate physicochemical characteristics and long term degradation features is essential. Polycaprolactone (PCL) presents the advantage to very slowly degrade itself following its molecular weight. This article evaluates two PCL materials, a technical (PC60: 60 kDa) versus a medical grade one (PC12: 80 kDa), both functionalized (or not) with poly(sodium styrene sulfonate) (pNaSS). After assessing the impact of the grafting process on the physicochemical properties, sheep ACL fibroblast responses were investigated. A better cell control in PC12 associated with an absence of inflammatory gene expression (TNF-α) was observed compared with PC60 films. Both types of films led to an overproduction of FGF-2 and TGF-β compared with the controls on day 5 and demonstrated collagen gene expression profiles similar to that of controls on day 7. Upon protein adsorption, pNaSS grafting caused a rapid cell adhesion (from 30 min) cumulated with an increase in adhesion strength (1.5-fold higher). Moreover, after 7 days, an increase in cell density and an important actin network development were noted.

Electrospun Poly(acrylic acid-co-4-styrene sulfonate) as Potential Drug-Eluting Scaffolds for Targeted Chemotherapeutic Delivery Systems on Gastric (AGS) and Breast (MDA-Mb-231) Cancer Cell Lines

“…Different investigations have reported this polymer to possess biocompatibility, antimicrobial capacity, non-immunogenic activity, and non-cytotoxicity [ 17 , 18 , 19 , 20 ]. Polymers containing AA or SS monomer units are reported in applications as bone tissue scaffolds [ 21 ], osteogenesis in vitro [ 22 ], films for biomedical applications [ 23 ], and graft responses for synthetic ligaments [ 24 ]. On the other hand, the electrospinning process possesses numerous advantages that make it an ideal technique to be used in drug releases, such as high surface-to-volume ratio, high porosity, numerous routes of administration, easy fabrication, and control of fiber characteristics [ 25 , 26 ].…”

rAAV TGF-β and FGF-2 Overexpression via pNaSS-Grafted PCL Films Stimulates the Reparative Activities of Human ACL Fibroblasts

“…These effects were accompanied by and probably due to increased levels of specific ECM-inducing transcription factors, Mohawk and scleraxis [ 20 , 35 ], in the hACL fibroblasts over extended periods of time (at least 21 days), especially when applying pNaSS-grafted PCL films versus control conditions and when compared with film-free vector solutions, results which are in overall agreement with the properties of these growth factors [ 36 , 37 ] and which extend our work using the current rAAV-hFGF-2 construct applied as a vector solution to hACL fibroblasts [ 12 ]. It is equally important that the delivery of rAAV-hTGF-β and rAAV-hFGF-2 via the PCL films had no detrimental effects on inflammatory processes (the production of IL-1β and TNF-α) in the hACL fibroblasts over time (at least 21 days), in concordance with the properties of these growth factors [ 38 , 39 , 40 ] and with the protective effects of the PCL films, especially following pNaSS grafting [ 26 ].…”

“…The poly(ε-caprolactone) (PCL) films ( Figure 8 B) were created via spin coating using an SPIN150-v3 SPS [ 25 , 26 , 27 ]. PCL (60% [ w / v ] in dichloromethane) was dropped for spinning on a glass slide (30 s at 1500 rpm).…”

“…Yet the clinical use of rAAV remains challenging due to existing barriers in the joint that may impede the effective overexpression of the therapeutic sequences delivered, including the presence of neutralizing antibodies against the viral AAV capsid in a majority of individuals and patients [ 24 ]. Based on the innovative concept of spatiotemporal biomaterial-guided gene therapy [ 9 ], the goal of the present study was to examine the potential of functionalized poly(sodium styrene sulfonate)-grafted poly(ε-caprolactone) (pNaSS-grafted PCL) films [ 25 , 26 , 27 ] to deliver functional therapeutic rAAV vectors coding for the reparative TGF-β and FGF-2 factors [ 10 , 11 , 12 ] in primary human ACL fibroblasts as an innovative, biomaterial-guided gene therapy strategy [ 28 , 29 ] and future off-the-shelf tool for enhancing the processes of ACL repair in patients.…”

Smart Mushroom-Inspired Imprintable and Lightly Detachable (MILD) Microneedle Patterns for Effective COVID-19 Vaccination and Decentralized Information Storage

“…In a rat model, a more biocompatible FITC dye was applied, consistent with in vitro labeling, suggesting a general labeling strategy. Considering the water solubility and quick diffusion of these dyes, a small amount of PCL was selected as a slow-degrading polyester to retard the dispersion of the dyes, extending the labeling period. ,, Notably, for both isolated porcine skin and living objects, the MILD microneedle patterns displayed clearly visible signals in a dotted matrix for quite a long time (at least 28 days longer than the most recommended vaccination intervals) without any obvious decay or photobleaching, , demonstrating excellent photostability. During this period, the vaccine protein amount in microneedles exhibited negligible alteration at room temperature, indicating a long-term storage stability of the vaccine in the MILD microneedle system, consistent with the previous study .…”