Biomaterials need to fulfill complex requirements, which are determined by a specific application. As such requirements can differ significantly from case to case, materials were developed, for which various properties [1,2] can be adjusted almost independently from each other. The choice of a suitable material and processes in order to allow the addition of desired functions is crucial and will only be effective when the underlying fundamental principles can be attributed to different structural elements on the molecular level. Multifunctional polymers that combine two functions such as shape-memory effect and biodegradability [3] or biodegradability and drug release [4] have been realized. However, a material that combines the three functions shape-memory capability, controlled drug release, and biodegradability has not yet been demonstrated. This would allow to combine the shape-memory effect for enabling minimally invasive implantation of bulky devices, [5] biodegradability to avoid a second surgery for implant removal, [6] and controlled drug release for treating infections, [7] reducing inflammatory responses, [8] or, later, supporting regeneration processes.[9] Such a combination of functions is demanded by biomaterial-assisted therapies, e.g., for vascular [10] and urinary stents or as scaffold material for reconstructive or aesthetic surgery (e.g., breast remodelling) [11] and in tissue engineering applications (e.g., bone regeneration).[12] Multimaterial systems presently applied in drug eluting stents cannot fulfill the complex demands, but the high level of interest they receive(d), [13] despite shortcomings and contraindications, [14] points to the necessity of new materials. Therefore, we explored whether three functions can be combined in one polymeric material.Our research strategy for the development of such a multifunctional polymer system was based on several key requirements that had to be met: i) the incorporation of hydrophilic and hydrophobic drugs shall not influence the shape-memory functionality, ii) a diffusion-controlled release that is independent from biodegradation must be enabled, and iii) the programming process and shape recovery, which a device experiences during minimally invasive implantation, shall not change the drug release kinetic. The rational design criteria that we derived from the results of our research for the molecular architecture of a suitable polymer system as well as synthesis and functionalization procedures are described in this paper.Shape-memory polymers consist of two key components: netpoints, determining the permanent form, and switching domains formed by switching segments, responsible for the fixation of the temporary shape.[15] Chemical netpoints (covalent crosslinks) have the advantage of ensuring high form stability of the permanent shape, while forming only a small mass fraction of the polymer networks. Fixation by switching domains has been realized by crystallization and vitrification.[16] The switching domains determine the switching temperature ...

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Implantation of a glaucoma drainage system is an appropriate therapeutic intervention in some glaucoma patients. However, one drawback with this approach is the fibrotic tissue response to the implant material, leading to reduced flow of aqueous liquid or complete blockage of the drainage system. As a basis for developing an aqueous shunt we report here investigations with poly(3-hydroxybutyrate) (P(3HB)) and poly(4-hydroxybutyrate) (P(4HB)) as polymer matrices and with paclitaxel (PTX) and triamcinolone acetonide (TA) as drugs that might, in combination, delay or prevent the process of fibrosis by reducing fibroblast activity. P(3HB) and P(4HB) were fabricated into test prototypes with 500 μm outer and 200 μm inner diameter and ∼1 cm length. The antiproliferative agent PTX and the anti-inflammatory agent TA were incorporated into the polymer matrices and were released by diffusion. In vitro cell assays demonstrated that the polymers have the potential to reduce fibroblast viability, while TA showed differential inhibition of Tenon fibroblasts, but not cornea keratocytes. Implantation of polymer disks and prototype devices into rabbit eyes confirmed the good biocompatibility of the materials. The combined use of a poly(hydroxybutyrate) polymer with PTX or TA has the potential to reduce the fibrosis associated with conventional glaucoma drainage systems.

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The drug diffusion of most compounds, particularly hydrophilic molecules through the skin is limited by the permeation of the outermost cell layers of the epidermis, the stratum corneum(SC). For this reason it is of interest to characterize drug diffusion processes through this skin layer. A new FTIR-ATR cell was developed for non-invasive real time measurements of drug diffusion. The diffusion of water through an artificial polyethyleneglycol-polydimethylsiloxane membrane was studied. Additionally the diffusion of urea in human SC was analyzed. Based on a mathematical model the diffusion coefficients were derived. We could reveal that this cell associates the advantages of the Franz diffusion cell and the FTIR-ATR spectroscopy as a new powerful method for determining drug diffusion through biological membranes.

Polymer networks synthesized by UV-curing of Oligo[(ε-caprolactone)-co-glycolide]dimethacrylates are hydolytically degradable. Their architecture with covalent netpoints and crystallizable domains is the molecular basis for the potential shape-memory capability. The molecular weight and glycolide content of the oligomeric precursors can be varied over a broad range of compositions to tailor the thermomechanical properties of the polymer network while having only a minor influence on the shape-memory effect. Recently, drug incorporation adding controlled drug release as further functionality to the polymer network was demonstrated [4]. Here, enoxacin and ethacridine lactate as test drugs were incorporated into the networks by soaking. Alternatively, defined amounts of ethacridine lactate were mixed with the precursors, which were subsequently crosslinked to the drug containing networks. The composition of the oligomeric precursors in molecular weight between 3800 and 12800 g�mol-1 and in glycolide content ϝG between 0 and 30 mol-% to explore the influence of the drug incorporation on networks with varying compositions while retaining properties and functionalities. Polymer networks prepared from precursors with ϝG ? 14 mol-% and Mn ? 6900 g�mol-1 have a Tsw of 35-52 �C and sufficient crystallinity to ensure a high shape fixity in the programming step. These limits have to be kept to ensure the desired multifunctionality, otherwise drug incorporation can have an undesired influence on thermal, mechanical, and shape-memory properties.

Summary: Hydrolytic degradation of poly(e-caprolactone) [PCL] can be enhanced by introduction of 8 wt.% glycolide leading to poly[(e-caprolactone)-co-glycolide] (PCG), which has a low elongation at break e B of 4%. PCG/PCL blends (50/50 w/w) combined the advantageous features of its individual components such as mechanical properties similar to pure PCL (e B, Blend : 900 AE 230%; e B, PCL : 730 AE 50 at 20 8C), water uptake rates during degradation similar to pure PCG, and linear mass loss during bulk degradation independent from sample dimensions. The outcome of cytotoxicity studies was depending on the cell type with promising results, e.g., for Tenon fibroblasts. Easy processing of the blend was demonstrated by melt compression, foaming with CO 2 , and hot melt extrusion, suggesting a wide applicability as biomaterial, e.g., as drug carrier.

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