Biodegradable functionalized membran for bone and tissue regeneration

Abstract

Bone defects of various sizes, resulting from trauma, malformations, pathological progressive degeneration, often require reconstructive bone augmentation procedures. The treatments have encompassed the utilization of a wide variety of surgical approaches, a series of bone grafts and barrier membranes. One of the best methods to realize bone regeneration in the area of the alveolar ridge is the application of guided bone-/guided tissue-regeneration (GBR/GTR) techniques. GTR is a surgical procedure that uses both non-degradable and biodegradable barrier membranes, to direct the growth of new tissues. While GTR deals with soft tissue, GBR focuses on separation of bone from the connective tissue to prevent its rapid ingrowth. Biodegradable collagen membranes are most often preferred to avoid an additional surgery of the patient to remove the non-degradable ones. However, conventional collagen membranes are usually unstable and can collapse into the defect under load. Furthermore, multidimensional bony defects require the application of volume-stable and load-bearing membranes, and that is currently only guaranteed by non-degradable synthetic materials. Thus, the clinical need to develop a next generation of volume-stable barrier membranes, that combine biocompatibility, structural stability and patient-specific shape with biodegradable properties is of great interest. In addition to their improved mechanical properties, a major advantage of such membranes would also be an active and specific promoting function in the regeneration processes of the tissues, as well as the exact and stable adjustment in the defect areas. Considering these aspects, the present project aims to develop, characterize and in-vitro and in-vivo investigate a new volume-stable barrier membrane composed of a biodegradable polymer polylactide (PLA), functionalized with nanoparticles and the growth factor bone morphogenetic protein 2 (BMP-2). There is still no approved close-fitting membrane on the European market that is enriched with growth factors (GFs), although they are considered to be effective in bone regeneration. The originality of the new membranes is the personalized shape, improved mechanical properties for better application and defined biodegradation. For the computer-aided 3D membranes design, exemplary Cone Beam Computed Topographical images of patients with small bony defects will be used. The advantage of this approach is on the one hand the precise adaptation of the membrane to the bone defects and teeth to maximize its stability and sealing and, on the other hand, the support of bone cells ingrowth into the defect site and the accelerated vascularization. Different structures and pore sizes, which are crucial for cell growth, offer two manufacturing processes: electrospinning and rapid, tomographic volumetric 3D printing, which are to be used in this project, in order to evaluate the most suitable method of manufacturing process including easy sterilization process as a compelling requirement for its clinical use. Performing in-vivo pre-clinical implantation tests shell assess the behavior of barrier membranes in an animal model to determine its true biomechanical integrity, biodegradation and vascularization properties as well as regeneration processes of bone und connecting tissues. In order to achieve the desired structure for manufacturing of the individualized membranes based on PLA, after a selection of suitable active nanoparticles the methods of electrospinning and volumetric 3Dprinting process should be used and subjected to shaping processes (TRL 2). The establishment of a digital process chain for a new personalized biodegradable membrane for the therapy of soft and bone tissue defects will be innovative and a great benefit in dentistry and medicine (TRL 4 at the end of the project). (AU)