Evaluation of pliable bioresorbable, elastomeric aortic valve prostheses in sheep during 12 months post implantation

Pliable microfibrous, bioresorbable elastomeric heart valve prostheses are investigated in search of sustainable heart valve replacement. These cell-free implants recruit cells and trigger tissue formation on the valves in situ. Our aim is to investigate the behaviour of these heart valve prostheses when exposed to the high-pressure circulation. We conducted a 12-month follow-up study in sheep to evaluate the in vivo functionality and neo-tissue formation of these valves in the aortic position. All valves remained free from endocarditis, thrombotic complications and macroscopic calcifications. Cell colonisation in the leaflets was mainly restricted to the hinge area, while resorption of synthetic fibers was limited. Most valves were pliable and structurally intact (10/15), however, other valves (5/15) showed cusp thickening, retraction or holes in the leaflets. Further research is needed to assess whether in-situ heart valve tissue engineering in the aortic position is possible or whether non-resorbable synthetic pliable prostheses are preferred.</p

Time-dependent failure in load-bearing polymers. A potential hazard in structural applications of polylactides

Polylactides are commonly praised for their excellent mechanical properties (e.g. a high modulus and yield strength). In combination with their bioresorbability and biocompatibility, they are considered prime candidates for application in load-bearing biomedical implants. Unfortunately, however, their long-term performance under static load is far from impressive. In a previous in vivo study on degradable polylactide spinal cages in a goat model it was observed that, although short-term mechanical and real-time degradation experiments predicted otherwise, the implants failed prematurely under the specified loads. In this chapter we demonstrate that this premature failure is attributed to the time-dependent character of the material used. The phenomenon is common to all polymers, and finds its origin in stress-activated segmental molecular mobility leading to a steady rate of plastic flow. The main conclusion is that knowledge of the instantaneous strength of a polymeric material is insufficient to predict its long-term performance

Rotational Isomerism of an Amide Substituted Squaraine Dye: A Combined Spectroscopic and Computational Study

The conformational analysis of a 2,4-bis(4-dialkylamino-2-amido)phenyl squaraine dye revealed the presence of two rotational isomers at room temperature. Combination of spectroscopic and computational techniques showed that the rotational barrier is influenced by hydrogen bonds between the amido substituents and the oxygen atoms at the quadratic core. Even small amounts of trifluoroacetic acid interfered with the intramolecular hydrogen bond formation and accelerated the interconversion of the conformers

Magnetic Resonance Monitoring of Opaque Temperature-Sensitive Polymeric Scaffolds

The monitoring of location and degradation rates of injectable biomaterials is an area of particular interest in the design and implementation of therapeutic scaffolds and carriers for tissue repair and replacement. We describe here the fabrication and characterization of gadolinium (Gd)-labeled temperature-responsive hydrogels that can be detected noninvasively using T1-weight magnetic resonance. Two acrylamide-functionalized GdIIIDOTA-monoamide complexes with either a short n-butylene spacer (GdIII-C4-AA) or a long hydrophilic spacer (GdIII-PEG-AA) were synthesized and incorporated into the hydrogels. At temperatures above the lower critical solution temperature (LCST), 37 °C, these hydrogels have the capacity to enhance relaxivity (r1) due to the hydrophobic interactions of the polyamide chains around the gadolinium chelates. This effect is further accentuated by the presence of the polyethylene glycol groups of the Gd complex GdIII-PEG-AA

Self-healing supramolecular polymers in action

Sophisticated polymeric materials with "responsive" properties, such as self-healing, are beginning to reach the market. Supramolecular polymers, i.e., polymers that owe their mechanical properties primarily to the reversible, non-covalent interactions, such as hydrogen bonding interactions, between the macromolecules, have frequently been employed as self-healing materials. The quadruple hydrogen bonding ureidopyrimidinone (UPy) unit is a particularly effective and versatile design motif, since it forms very strong but reversible linkages, and can be incorporated into virtually any type of polymer backbone, leading to materials with increased mechanical properties. Supramolecular polymers are presented, with an emphasis on those based on the UPy-unit, and their use in self-healing applications is highlighted and discussed. Supramolecular polymers are eminently useful in self-healing applications. The reversible nature of supramolecular polymers allows for self-healing processes to take place, using a contact pressure trigger or a heat trigger. Several materials are presented with an emphasis on ureidopyrimidinone (UPy) comprising supramolecular polymer

Supramolecular Additive-Initiated Controlled Atom Transfer Radical Polymerization of Zwitterionic Polymers on Ureido-pyrimidinone-Based Biomaterial Surfaces

Surface-initiated controlled radical polymerization is a popular technique for the modification of biomaterials with, for example, antifouling polymers. Here, we report on the functionalization of a supramolecular biomaterial with zwitterionic poly(sulfobetaine methacrylate) via atom transfer radical polymerization from a macroinitiator additive, which is embedded in the hard phase of the ureido-pyrimidinone-based material. Poly(sulfobetaine methacrylate) was successfully polymerized from these surfaces, and the polymerized sulfobetaine content, with corresponding antifouling properties, depended on both the macroinitiator additive concentration and polymerization time. Furthermore, the polymerization from the macroinitiator additive was successfully translated to functional electrospun scaffolds, showing the potential for this functionalization strategy in supramolecular material systems. ©</p

Host response and neo-tissue development during resorption of a fast degrading supramolecular electrospun arterial scaffold

In situ vascular tissue engineering aims to regenerate vessels “at the target site” using synthetic scaffolds that are capable of inducing endogenous regeneration. Critical to the success of this approach is a fine balance between functional neo-tissue formation and scaffold degradation. Circulating immune cells are important regulators of this process as they drive the host response to the scaffold and they play a central role in scaffold resorption. Despite the progress made with synthetic scaffolds, little is known about the host response and neo-tissue development during and after scaffold resorption. In this study, we designed a fast-degrading biodegradable supramolecular scaffold for arterial applications and evaluated this development in vivo. Bisurea-modified polycaprolactone (PCL2000-U4U) was electrospun in tubular scaffolds and shielded by non-degradable expanded polytetrafluoroethylene in order to restrict transmural and transanastomotic cell ingrowth. In addition, this shield prevented graft failure, permitting the study of neo-tissue and host response development after degradation. Scaffolds were implanted in 60 healthy male Lewis rats as an interposition graft into the abdominal aorta and explanted at different time points up to 56 days after implantation to monitor sequential cell infiltration, differentiation, and tissue formation in the scaffold. Endogenous tissue formation started with an acute immune response, followed by a dominant presence of pro-inflammatory macrophages during the first 28 days. Next, a shift towards tissue-producing cells was observed, with a striking increase in α-Smooth Muscle Actin-positive cells and extracellular matrix by day 56. At that time, the scaffold was resorbed and immune markers were low. These results suggest that neo-tissue formation was still in progress, while the host response became quiescent, favoring a regenerative tissue outcome. Future studies should confirm long-term tissue homeostasis, but require the strengthening of the supramolecular scaffold if a non-shielded model will be used

Supramolecular Additive-Initiated Controlled Atom Transfer Radical Polymerization of Zwitterionic Polymers on Ureido-pyrimidinone-Based Biomaterial Surfaces

Surface-initiated controlled radical polymerization is a popular technique for the modification of biomaterials with, for example, antifouling polymers. Here, we report on the functionalization of a supramolecular biomaterial with zwitterionic poly(sulfobetaine methacrylate) via atom transfer radical polymerization from a macroinitiator additive, which is embedded in the hard phase of the ureido-pyrimidinone-based material. Poly(sulfobetaine methacrylate) was successfully polymerized from these surfaces, and the polymerized sulfobetaine content, with corresponding antifouling properties, depended on both the macroinitiator additive concentration and polymerization time. Furthermore, the polymerization from the macroinitiator additive was successfully translated to functional electrospun scaffolds, showing the potential for this functionalization strategy in supramolecular material systems. ©</p

Marker-Independent Monitoring of in vitro and in vivo Degradation of Supramolecular Polymers Applied in Cardiovascular in situ Tissue Engineering

The equilibrium between scaffold degradation and neotissue formation, is highly essential for in situ tissue engineering. Herein, biodegradable grafts function as temporal roadmap to guide regeneration. The ability to monitor and understand the dynamics of degradation and tissue deposition in in situ cardiovascular graft materials is therefore of great value to accelerate the implementation of safe and sustainable tissue-engineered vascular grafts (TEVGs) as a substitute for conventional prosthetic grafts. In this study, we investigated the potential of Raman microspectroscopy and Raman imaging to monitor degradation kinetics of supramolecular polymers, which are employed as degradable scaffolds in in situ tissue engineering. Raman imaging was applied on in vitro degraded polymers, investigating two different polymer materials, subjected to oxidative and enzymatically-induced degradation. Furthermore, the method was transferred to analyze in vivo degradation of tissue-engineered carotid grafts after 6 and 12 months in a sheep model. Multivariate data analysis allowed to trace degradation and to compare the data from in vitro and in vivo degradation, indicating similar molecular observations in spectral signatures between implants and oxidative in vitro degradation. In vivo degradation appeared to be dominated by oxidative pathways. Furthermore, information on collagen deposition and composition could simultaneously be obtained from the same image scans. Our results demonstrate the sensitivity of Raman microspectroscopy to determine degradation stages and the assigned molecular changes non-destructively, encouraging future exploration of this techniques for time-resolved quality assessment of in situ tissue engineering processes