Recent Developments in Layer-by-Layer Assembly for Drug Delivery and Tissue Engineering Applications.

Surfaces with biological functionalities are of great interest for biomaterials, tissue engineering, biophysics, and for controlling biological processes. The layer-by-layer (LbL) assembly is a highly versatile methodology introduced 30 years ago, which consists of assembling complementary polyelectrolytes or biomolecules in a stepwise manner to form thin self-assembled films. In view of its simplicity, compatibility with biological molecules, and adaptability to any kind of supporting material carrier, this technology has undergone major developments over the past decades. Specific applications have emerged in different biomedical fields owing to the possibility to load or immobilize biomolecules with preserved bioactivity, to use an extremely broad range of biomolecules and supporting carriers, and to modify the film's mechanical properties via crosslinking. In this review, the focus is on the recent developments regarding LbL films formed as 2D or 3D objects for applications in drug delivery and tissue engineering. Possible applications in the fields of vaccinology, 3D biomimetic tissue models, as well as bone and cardiovascular tissue engineering are highlighted. In addition, the most recent technological developments in the field of film construction, such as high-content liquid handling or machine learning, which are expected to open new perspectives in the future developments of LbL, are presented.

3D-Printed Osteoinductive Polymeric Scaffolds with Optimized Architecture to Repair a Sheep Metatarsal Critical-Size Bone Defect.

The reconstruction of critical-size bone defects in long bones remains a challenge for clinicians. A new osteoinductive medical device is developed here for long bone repair by combining a 3D-printed architectured cylindrical scaffold made of clinical-grade polylactic acid (PLA) with a polyelectrolyte film coating delivering the osteogenic bone morphogenetic protein 2 (BMP-2). This film-coated scaffold is used to repair a sheep metatarsal 25-mm long critical-size bone defect. In vitro and in vivo biocompatibility of the film-coated PLA material is proved according to ISO standards. Scaffold geometry is found to influence BMP-2 incorporation. Bone regeneration is followed using X-ray scans, µCT scans, and histology. It is shown that scaffold internal geometry, notably pore shape, influenced bone regeneration, which is homogenous longitudinally. Scaffolds with cubic pores of ≈870 µm and a low BMP-2 dose of ≈120 µg cm-3 induce the best bone regeneration without any adverse effects. The visual score given by clinicians during animal follow-up is found to be an easy way to predict bone regeneration. This work opens perspectives for a clinical application in personalized bone regeneration.

Additive Manufacturing of Material Scaffolds for Bone Regeneration: Toward Application in the Clinics.

Additive manufacturing (AM) allows the fabrication of customized bone scaffolds in terms of shape, pore size, material type and mechanical properties. Combined with the possibility to obtain a precise 3D image of the bone defects using computed tomography or magnetic resonance imaging, it is now possible to manufacture implants for patient-specific bone regeneration. This paper reviews the state-of-the-art of the different materials and AM techniques used for the fabrication of 3D-printed scaffolds in the field of bone tissue engineering. Their advantages and drawbacks are highlighted. For materials, specific criteria, were extracted from a literature study: biomimetism to native bone, mechanical properties, biodegradability, ability to be imaged (implantation and follow-up period), histological performances and sterilization process. AM techniques can be classified in three major categories: extrusion-based, powder-based and liquid-base. Their price, ease of use and space requirement are analyzed. Different combinations of materials/AM techniques appear to be the most relevant depending on the targeted clinical applications (implantation site, presence of mechanical constraints, temporary or permanent implant). Finally, some barriers impeding the translation to human clinics are identified, notably the sterilization process.