Varying the sustained release of BMP-2 from chitosan nanogel-functionalized polycaprolactone fiber mats by different polycaprolactone surface modifications.

Julius Sundermann,Steffen Sydow,Henning Menzel,Robert Hänsch,Bastian Quaas,Ursula Rinas,Sarah Oehmichen,Andrea Hoffmann,Laura Burmeister,Heike Bunjes

doi:10.1002/jbm.a.37045

Abstract

Polycaprolactone (PCL) fiber mats with different surface modifications were functionalized with a chitosan nanogel coating to attach the growth factor human bone morphogenetic protein 2 (BMP-2). Three different hydrophilic surface modifications were compared with regard to the binding and in vitro release of BMP-2. The type of surface modification and the specific surface area derived from the fiber thickness had an important influence on the degree of protein loading. Coating the PCL fibers with polydopamine resulted in the binding of the largest BMP-2 quantity per surface area. However, most of the binding was irreversible over the investigated period of time, causing a low release in vitro. PCL fiber mats with a chitosan-graft-PCL coating and an additional alginate layer, as well as PCL fiber mats with an air plasma surface modification boundless BMP-2, but the immobilized protein could almost completely be released. With polydopamine and plasma modifications as well as with unmodified PCL, high amounts of BMP-2 could also be attached directly to the surface. Integration of BMP-2 into the chitosan nanogel functionalization considerably increased binding on all hydrophilized surfaces and resulted in a sustained release with an initial burst release of BMP-2 without detectable loss of bioactivity in vitro.

Highlights

The local application of cytokines, including growth factors, to stimulate regeneration processes in damaged tissue is a promising field of regenerative medicine
Because of its positive charge, a pronounced tendency to enter into hydrophobic interactions via its hydrophobic patches (Utesch, Daminelli, & Mroginski, 2011), and its affinity to glycosaminoglycans such as heparin or to domains like fibronectin type III (Martino et al, 2011), bone morphogenetic protein 2 (BMP-2) can be very efficiently bound to surfaces (Marquetti & Desai, 2018; Ruppert, Hoffmann, & Sebald, 1996)
Hettiaratchi et al investigated the binding of BMP-2 to heparin microparticles and found that about 87% of the total amount of BMP2 was bound to the microparticles after 30 min, which increased to 91% after 90 min and reached a maximum after 4 hr (Hettiaratchi et al, 2017)

Summary

Introduction

The local application of cytokines, including growth factors, to stimulate regeneration processes in damaged tissue is a promising field of regenerative medicine. One approach to close this gap is to use natural or synthetic biomaterials that can provide the required properties of these tissue transitions Such artificial scaffolds lack the necessary bioactive triggers for directed tissue repair (Longo, Lamberti, Rizzello, Maffulli, & Denaro, 2012). To restore the tissue transition between bone and tendon, a scaffold structure is required in which growth factors can exert their stimulating effect on cell recruitment and growth. For this purpose, electrospun polycaprolactone (PCL) is a promising biodegradable and FDA-approved material to mimic the extracellular environment of tendon tissue. Limitations of biocompatibility as a result of the high hydrophobicity of PCL can be overcome by surface modifications (Gniesmer et al, 2019)

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