Novel Surface Coatings Using Oxidized Glycosaminoglycans as Delivery Systems of Bone Morphogenetic Protein 2 (BMP‐2) for Bone Regeneration

Abstract

Tissue engineering of bone requires the delivery of growth factors in a localized, sustained manner. Here, chitosan is used as polycation, while heparin and chondroitin sulfate are employed either as native or oxidized polyanions for formation of multilayers by layer‐by‐layer technique. The use of oxidized heparin and oxidized chondroitin sulfate permits additional stabilization by cross‐linking through imine bond formation between amino groups of polycations and aldehydes of oxidized glycosaminoglycans (oGAGs). Since these multilayers are highly hydrophilic, adhesion of C2C12 myoblasts is improved either by the use of a specific 4 + 9 pH regime with native glycosaminoglycans or a terminal collagen I layer in case of oGAGs. Adhesion and proliferation studies with C2C12 myoblasts, seeded either on bone morphogenetic protein (BMP‐2) loaded or non‐loaded multilayers, show that intrinsic cross‐linking in oGAG‐based multilayers supports cell adhesion, spreading, proliferation, and subsequent cell differentiation into osteoblasts. This is related to higher thickness and roughness of multilayers made of oGAGs compared to their native counterparts studied by ellipsometry and atomic force microscopy. Taken together, oGAG multilayer systems provide stable surface coatings and are useful as biocompatible reservoirs for sustained release of BMP‐2, paving the way for coating implants and scaffolds for repair and regeneration of bone.

Heparan sulfate co-immobilized with cRGD ligands and BMP2 on biomimetic platforms promotes BMP2-mediated osteogenic differentiation

“…In the osteogenic context, various approaches have been reviewed recently [18,19], all focusing on presenting GFs via ECM molecules such as proteins and GAGs. For example, polyelectrolyte multilayer films can be engineered with tunable stiffness [20] and trap BMP2 with high affinity [21,22]. To study the isolated or combined effect of single ECM components on cells, versatile surfaces with precise control of molecular orientation and surface density are needed.…”

Effect of Different Crosslinking Strategies on Physical Properties and Biocompatibility of Freestanding Multilayer Films Made of Alginate and Chitosan

“…[8][9][10] An important advantage of LbL technique is that the layer-wise formation of films also permits the loading of bioactive molecules, such as pharmaceuticals and growth factors with the final aim of providing a biomimetic microenvironment for control of cell behavior. [11] Different types of biomaterials of natural origin have been used for biomedical applications. [12,13] One large family of natural polymers are polysaccharides, which exhibit high hydration rates, are abundant, biocompatible, and very often biodegradable.…”

“…LbL has been acknowledged as a feasible method to produce novel biomaterials due to its ease of use, versatility, and ability to incorporate different molecules, as well as the ability to control topography, microarchitecture, and biomechanics of coatings, films, capsules, nano and micro particles . An important advantage of LbL technique is that the layer‐wise formation of films also permits the loading of bioactive molecules, such as pharmaceuticals and growth factors with the final aim of providing a biomimetic microenvironment for control of cell behavior …”

Electrical Field-Assisted Gene Delivery from Polyelectrolyte Multilayers

“…This versatile technique can be utilized for drug delivery because the release of polyelectrolytes depends highly on the structure and composition of polyelectrolyte multilayers (PEMs) [1]. Drug delivery through PEMs give good spatial control; thus, this method can be applied to different medical devices such as stents [2,3], intraocular lens [4], dental implants [5], tissue engineering scaffolds [6,7], wound dressings [8,9], and bone grafts [10,11], by which not only drugs can be locally delivered to the target sites but their therapeutic effects can also be extended through the continuous releases. Nucleotides, such as siRNA and DNA, are especially suitable for controlled delivery through PEMs because these anionic biomacromolecules can be immobilized with polycations easily through LbL assembly [12][13][14][15][16].…”