Hydrogels based on collagen and fibrin - Frontiers and applications

Hydrogels are a versatile tool for a multitude of applications in biomedical research and clinical practice. Especially collagen and fibrin hydrogels are distinguished by their excellent biocompatibility, natural capacity for cell adhesion and low immunogenicity. In many ways, collagen and fibrin represent an ideal biomaterial, as they can serve as a scaffold for tissue regeneration and promote the migration of cells, as well as the ingrowth of tissues. On the other hand, pure collagen and fibrin materials are marked by poor mechanical properties and rapid degradation, which limits their use in practice. This paper will review methods of modification of natural collagen and fibrin materials to next-generation materials with enhanced stability. A special focus is placed on biomedical products from fibrin and collagen already on the market. In addition, recent research on the in vivo applications of collagen and fibrin-based materials will be showcased. © 2016 by De Gruyter

Chemically induced hypoxia by dimethyloxalylglycine (dmog)-loaded nanoporous silica nanoparticles supports endothelial tube formation by sustained vegf release from adipose tissue-derived stem cells

Inadequate vascularization leading to insufficient oxygen and nutrient supply in deeper layers of bioartificial tissues remains a limitation in current tissue engineering approaches to which prevascularization offers a promising solution. Hypoxia triggering pre-vascularization by enhanced vascular endothelial growth factor (VEGF) expression can be induced chemically by dimethyloxalylglycine (DMOG). Nanoporous silica nanoparticles (NPSNPs, or mesoporous silica nanoparticles, MSNs) enable sustained delivery of molecules and potentially release DMOG allowing a durable capillarization of a construct. Here we evaluated the effects of soluble DMOG and DMOG-loaded NPSNPs on VEGF secretion of adipose tissue-derived stem cells (ASC) and on tube formation by human umbilical vein endothelial cells (HUVEC)-ASC co-cultures. Repeated doses of 100 mM and 500 mM soluble DMOG on ASC resulted in 3- to 7-fold increased VEGF levels on day 9 (P<0.0001). Same doses of DMOG-NPSNPs enhanced VEGF secretion 7.7-fold (P<0.0001) which could be maintained until day 12 with 500 mM DMOG-NPSNPs. In fibrin-based tube formation assays, 100 mM DMOG-NPSNPs had inhibitory effects whereas 50 mM significantly increased tube length, area and number of junctions transiently for 4 days. Thus, DMOG-NPSNPs supported endothelial tube formation by upregulated VEGF secretion from ASC and thus display a promising tool for prevascularization of tissue-engineered constructs. Further studies will evaluate their effect in hydrogels under perfusion

Establishment of a Modular Hemodynamic Simulator for Accurate In Vitro Simulation of Physiological and Pathological Pressure Waveforms in Native and Bioartificial Blood Vessels

Purpose!#!In vitro stimulation of native and bioartificial vessels in perfusable systems simulating natural mechanical environments of the human vasculature represents an emerging approach in cardiovascular research. Promising results have been achieved for applications in both regenerative medicine and etiopathogenetic investigations. However, accurate and reliable simulation of the wide variety of physiological and pathological pressure environments observed in different vessels still remains an unmet challenge.!##!Methods!#!We established a modular hemodynamic simulator (MHS) with interchangeable and modifiable components suitable for the perfusion of native porcine-(i.e. the aorta, brachial and radial arteries and the inferior vena cava) and bioartificial fibrin-based vessels with anatomical site specific pressure curves. Additionally, different pathological pressure waveforms associated with cardiovascular diseases including hyper- and hypotension, tachy- and bradycardia, aortic valve stenosis and insufficiency, heart failure, obstructive cardiomyopathy and arterial stiffening were simulated. Pressure curves, cyclic distension and shear stress were measured for each vessel and compared to ideal clinical pressure waveforms.!##!Results!#!The pressure waveforms obtained in the MHS showed high similarity to the ideal anatomical site specific pressure curves of different vessel types. Moreover, the system facilitated accurate emulation of physiological and different pathological pressure conditions in small diameter fibrin-based vessels.!##!Conclusion!#!The MHS serves as a variable in vitro platform for accurate emulation of physiological and pathological pressure environments in biological probes. Potential applications of the system include bioartificial vessel maturation in cardiovascular tissue engineering approaches as well as etiopathogenetic investigations of various cardiovascular pathologies

Dehydration improves biomechanical strength of bioartificial vascular graft material and allows its long-term storage

We have recently reported about a novel technique for the generation of bioartificial vascular grafts based on the use of a compacted fibrin matrix. In this study, we evaluated the effects of a dehydration process on the biomechanical properties of compacted fibrin tubes and whether it allows for their long-term storage

Laser fabrication of 3D gelatin scaffolds for the generation of bioartificial tissues

In the present work, the two-photon polymerization (2PP) technique was applied to develop precisely defined biodegradable 3D tissue engineering scaffolds. The scaffolds were fabricated via photopolymerization of gelatin modified with methacrylamide moieties. The results indicate that the gelatin derivative (GelMod) preserves its enzymatic degradation capability after photopolymerization. In addition, the developed scaffolds using 2PP support primary adipose-derived stem cell (ASC) adhesion, proliferation and differentiation into the anticipated lineage

Conventional culture diagnostics vs. multiplex PCR for the detection of causative agents of vascular graft infections - results of a single centre observational pilot study

Background: Timely diagnosis of vascular graft infections is of major importance in vascular surgery. The detection of causative microorganisms is needed for specific medical treatment, but conventional culture is often slow, insensitive and inconclusive due to antibiotic pre-treatment. Detection of bacterial DNA by polymerase chain reaction (PCR) might bypass these problems. We hypothesised that multiplex PCR (mPCR) is feasible, fast and sensitive to detect causative microorganisms in vascular graft infections. Patients and methods: We performed a pilot observational prospective study comparing conventional culture and a commercial mPCR. Inclusion criteria were: confirmed graft infection, suspicious imaging, clinical suspicion, anastomotic aneurysm and repeated graft occlusion. Diagnostic methods were performed using identical samples. Time to result, microorganisms and antibiotic resistance in both groups were compared using Student's t-test or nonparametric tests. Results: 22 samples from 13 patients were assessed and 11 samples were negative for bacteria. Some showed multiple germs. In total, we found 15 different organisms. 13 samples matched, 9 had non-concordant results. Out of the mismatches 3 microorganisms identified in PCR were not detected by culture. Time to result with PCR was shorter (median 5 h vs. 72 h, p < 0.001) than with culture. No resistance genes were detected by mPCR, but conventional culture allowed susceptibility testing and revealed resistance in 5 samples. Conclusions: mPCR seems to be a feasible and quick tool to detect causes of vascular graft infections within 24 h and might be helpful in antibiotic pre-treated patients. The detection of antibiotic resistance with mPCR needs improvement for clinical practice

Tissue Engineering of Viable Pulmonary Arteries for Surgical Correction of Congenital Heart Defects

BackgroundTissue-engineered pulmonary arteries could overcome the drawbacks of homografts or prosthetic conduits used in the repair of many congenital cardiac defects. However, the ideal scaffold material for tissue-engineered conduits is still subject of intensive debate. In this study, we evaluated an acellularized allogeneic matrix scaffold for pulmonary artery tissue engineering with and without in-vitro reseeding with autologous endothelial cells in the pulmonary circulation in a growing sheep model.MethodsOvine pulmonary arteries (n = 10) were acellularized by trypsin/ethylenediamine tetraacetic acid incubation. Autologous endothelial cells were harvested from carotid arteries, and the pulmonary conduits were seeded with endothelial cells. We implanted in-vitro, autologous, reendothelialized (group A, n = 5) and acellularized pulmonary conduits (group B, n = 5) in the pulmonary circulation. The animals were sacrificed 6 months after the operation. Explanted valves were examined histologically and by immunohistochemistry.ResultsThe conduit diameter increased in both groups (group A, 44% ± 11%; group B, 87% ± 18%; p < 0.05). In group A, however, a proportional increase in diameter was present, whereas in group B, a disproportionate increase resulting in aneurysm formation was observed. Histologically, the conduit wall integrity was destroyed in group B and preserved in group A. In group B, the extracellularmatrix degenerated with a reduced amount of collagens and proteoglycanes. Furthermore, no elastic fibers were detectable. In contrast, the extracellularmatrix in group A was close to native ovine tissue.ConclusionsTissue-engineered pulmonary conduits (autologous endothelial cells and allogeneic matrix scaffolds) functioned well in the pulmonary circulation. They demonstrated an increase in diameter and an extracellular matrix comparable to that of native ovine tissue