Biomaterials are instrumental in individualized medical technologies targeting regenerative therapies, immunomodulation or diagnostic methods. In addition to direct clinical application, biomaterials play a key role in the development of advanced three-dimensional tissue and disease models as, for example, required in personalized drug screening.
The one-day symposium is organized by three institutes of Leibniz Health Technologies: the Leibniz Institute of New Materials (INM), the Leibniz Institute for Interactive Materials (DWI) and the Leibniz Institute of Polymer Research Dresden (IPF). Those three institutes work in close collaboration within the LGT competence area “Bioactive Interfaces”.
The event will focus on recent developments in adaptive and bioactive materials for individualized approaches of medical technologies. Beyond recent advances in biomaterials science, the symposium will cover the translational perspective, provide an industrial point of view, and give insights on related aspects of health economy and research policy.
KARL STORZ Visitor and Training Centre, Berlin
Scharnhorststraße 3 | 10115 Berlin
22 March 2017, 09:30 – 17:00
Welcome address by the organizers:
Matthias P. Lutolf
Institute of Bioengineering and Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland
The earliest steps of development are characterized by cellular reorganization and differentiation within a three-dimensional (3D) microenvironment. This 3D context allows for a complex spatial interplay between biochemical and mechanical signals, and governs important cellular rearrangements leading to morphogenesis. In vitro approaches have attempted to capture key features of these processes, and it has now become possible to generate an increasing variety of self-organizing multicellular tissue constructs termed ‘organoids’. While these approaches are incredibly promising, a number of limitations exist that preclude their reliable use. In particular, the poor reproducibility, dependency on ill-defined matrices, and current inability to scale these assays need to be addressed to make organoid models useful for pharmacological applications and personalized medicine. In this talk, I will highlight recent efforts in my lab to grow organoids in fully defined synthetic hydrogels.
Laura De Laporte
Spinal cord injury affects approximately two million people worldwide and leads to a permanent loss of motor and sensory function below the point of injury. Repair is impeded due to the lack of stimulating growth factors, the presence of inhibiting molecules, and the formation of a cavity and scar tissue. Here, we present a low invasive therapy to support nerve regeneration, based on an injectable hydrogel with the ability to form an anisotropic structure in situ and induce aligned nerve growth, even in the presence of minimal guidance cues. The developed Anisogel represents the first biomaterial that can achieve highly controlled and ordered structures after injection to guide tissue repair with the correct architecture.
Department for Functional Materials in medicine and Dentistry, University Hospital Würzburg
Hydrogels are three-dimensionally cross-linked hydrophilic polymer networks in which cells can be embedded similar like in the extra cellular matrix of many tissues. Only recently, the combination with 3D printing has led to development of printable hydrogels for direct genera-tion of hierarchical structures that allow mimicry of tissue like morphologies. Moreover, the polymer network in hydrogels protects embedded bioactives such as proteins and peptides from degradation, and the degradability of the network can be adjusted through the chemical design of the polymers and the choice of cross-linking mechanism. This lecture will give an overview on different approaches for the generation of hierarchical cell-biomaterial constructs as strategy to tissue and patient specific therapies.
BIOSS Centre for Biological Signalling Studies, University of Freiburg
Biomaterials hold high promises for the development of analytical and therapeutic devices in diagnostics or drug delivery – especially when their mechanical and biological properties can be dynamically controlled by pharmacological or optical cues. We present chemically controlled biomaterials for the inducible, externally triggered release of therapeutics or optically responsive materials for assessing how cells integrate dynamic mechanical cues. We further demonstrate how semi-conducting nanomaterials can be combined with biological sensor modules for the quasi-real-time quantification of drugs e.g. in personalized therapeutic drug monitoring.
Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration, Charité – Universitätsmedizin Berlin
Understanding cascades of endogenous regeneration in bone (leading to restitutio ad integrum) may serve as blueprint even for tissues currently leading to scar formation. The multistage regenerative cascade is initiated in response to injury and vessel disruption with a well-orchestrated inflammatory response. Specific immune cell subsets of the adaptive immune system influence the regenerative healing capacity after fracture. The impact of the immune cells on the quality of the newly formed, hierarchically organized bone tissue however, have so for not been fully understood.
Andrés J. García
Hydrogels, highly hydrated cross-linked polymer networks, have emerged as powerful synthetic analogs of extracellular matrices for basic cell studies as well as promising biomaterials for regenerative medicine applications. A critical advantage of these synthetic matrices over natural networks is that bioactive functionalities, such as cell adhesive sequences and growth factors, can be incorporated in precise densities while the substrate mechanical properties are independently controlled. We have engineered poly(ethylene glycol) [PEG]-maleimide hydrogels to support the development of stem cell-derived organoids. In another application, we have developed synthetic hydrogels that support improved pancreatic islet engraftment, vascularization and function in diabetic models. These studies establish these biofunctional hydrogels as promising platforms for basic science studies and biomaterial carriers for cell delivery, engraftment and enhanced tissue repair.
Leibniz Institute of New Materials (INM), Saarbrücken
The biochemical constitution and physical properties of natural tissues progressively change over their lifetime and dramatically vary in pathological states like cancer. These changes are sensed by the embedded cells, and can trigger cellular processes and transitions. At INM-Leibniz Institute for New Materials we develop biomaterials to recreate dynamic cellular scenarios of biomedical relevance. These can be applied to guide cell-materials interactions in vitro and in vivo. Optoregulated biomaterials represent powerful platforms for screening intricate biological phenomena in natural environments, for constructing personalized tissue and disease models and advanced scaffolds for cell therapies.
Institute of Biofunctional Polymer Materials, Leibniz Institute of Polymer Research Dresden (IPF)
Modular biohybrid hydrogels for multifunctional wound dressings Wound healing is governed by cytokines regulating cell migration, inflammatory activity and proliferation. Dysregulations of these signals can result in chronic wounds. Glycosaminoglycans (GAGs) control the activity of cytokines in vivo. We report a modular biohybrid hydrogel system based on star-shaped PEG, the GAG heparin, and functional peptides. The materials can scavenge pro-inflammatory cytokines and deliver anti-inflammatory cytokines as well as growth factors capable of inducing angiogenesis and tissue maturation. Wound healing studies in diabetic mice demonstrate the potential of PEG-GAG hydrogels for creating anti-inflammatory, pro-regenerative conditions.
Institute for Clinical & Experimental Surgery, Saarland University
The dorsal skinfold chamber is a model for the analysis of the dynamic interaction of biomaterials with the host tissue in rats, hamsters and mice. By means of intravital fluorescence microscopy, this chronic model allows repetitive analyses of molecular and cellular mechanisms that are involved in the inflammatory and angiogenic response to biomaterials during the initial 2-3 weeks after implantation. Therefore, it has been broadly used for the in vivo evaluation of different biomaterials, such as surgical meshes, bone substitutes or scaffolds for tissue engineering. These studies have contributed to identify basic material properties determining the implants’ biocompatibility, vascularization and incorporation. Thus, the dorsal skinfold chamber does not only provide new insights into complex biomaterial-tissue interactions but is also suitable for the development of biomaterials with an improved biofunctionality.
The market for medical implant technology is characterized by continuous innovation. Crucial to the adoption of innovations in the field of medical devices, such as implants, are better clinical outcomes as well as enhanced patient benefits combined with an increase in cost effectiveness in comparison to the current standard in therapy. The process of innovation is not only characterized by a novel product as such. The stakeholders involved in addition to various promotors and barriers influence the adoption of an innovation significantly. [Fleßa et al. 2013] Identifying inhibitors as well as promotors influencing the innovation process is key to managing the adoption of innovative implants. A model on the innovation process of novel implant technology will be presented mapping these influencing factors. By means of this model the adoption process of an innovative implant can be simulated as well as instruments encouraging promotors and overcoming barriers implemented in order to create a successful adoption strategy.
Excellent research and development activities are the first important steps for future innovations. The major challenge is to bring together all the necessary strands of an innovation policy, to match the right people and institutions and ideas.This is where federal funding policy is crucial: to build a sustainable innovation ecosystem with an inherent systematic approach that includes material design and polymeric device development as well as processing, regulative obligations, economic necessities and individual needs. To find the right “ingredients” for an ecosystem for biomaterials-based approaches for personalized medicine is a challenge, but worth the endeavor to improve the quality of life of our citizens.