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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 ...

Degradable shape-memory polymer networks intended for biomedical applications were synthesized from oligo-[( -hydroxycaproate)-co-glycolate]dimethacrylates with glycolate contents between 0 and 30 mol % using a photopolymerization process. In addition AB copolymer networks were prepared by adding 60 wt % n-butyl acrylate as comonomer. All synthesized polymer networks are semicrystalline at room temperature. A melting transition T m between 18 and 53°C which can be used as switching transition for the shape-memory effect can be attributed to the crystalline poly( -hydroxycaproate) phase. At temperatures below T m the elastic properties are dominated by these physical cross-links. At temperatures higher than T m the E modulus of the amorphous polymer networks is lowered by up to 2 orders of magnitude, depending on the chemical cross-link density. Copolymer networks based on macrodimethacrylates with a M n of up to 13 500 g‚mol -1 and a maximum glycolate content of 21 mol % show quantitative strain recovery rates in stress-controlled cyclic thermomechanical experiments. Hydrolytic degradation experiments of polymer networks performed in phosphate buffer solution at 37°C show that the degradation rate can be accelerated by increasing the glycolate content and decelerated by the incorporation of n-butyl acrylate. IntroductionMaterials which obtain their functionality after application of a functionalization process such as that described for shapememory polymers can be referred to as functionalized materials. 1 An actual trend in polymer science is the design of materials which show multifunctionality, meaning an unexpected combination of material functionalizations such as the combination of hydrolytic degradability and shape-memory functionality. [2][3][4] The shape-memory effect results from the combination of the polymer architecture with a certain processing and programming technology. The permanent shape of shape-memory polymers is defined by physical or chemical cross-links, while switching segments formed by domains, which are associated with a thermal transition T trans. , enable the fixation of the temporary shape. 1,5 To obtain a defined shape change upon transition of a switching temperature T switch , the temporary shape has to be programmed by application of a thermomechanical treatment. Examples for polymers which combine shape-memory functionality and biodegradability are amorphous polyesterurethane networks based on poly(rac-lactide-co-glycolate) segments having a glass transition temperature T g around 55°C. 5 Poly-[(3-hydroxybutyrate)-co-(3-hydroxyvalerate) (35 mol % 3-hydroxyvalerate) obtained by a biotechnological process showed a shape-memory effect when samples which were programmed by a cold drawing were submitted to temperatures above 75°C. The melting transition used to trigger the shape-memory effect and to define the permanent shape simultaneously ranged from 37 to 115°C. 6 Examples for polymers showing a thermally induced shapememory effect which contain poly( -hydroxycaproate), being con...

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Semi-crystalline AB-copolymer networks from oligo[(epsilon-caprolactone)-co-glycolide]dimethacrylates and n-butylacrylate have recently been shown to exhibit a shape-memory functionality, which may be used for self-deploying and anchoring of implants. In this study, a family of such materials differing in their molar glycolide contents chi(G) was investigated to determine structure-property functional relationships of unloaded and drug loaded specimens. Drug loading and release were evaluated, as well as their degradation behavior in vitro and in vivo. Higher chi(G) resulted in higher loading levels by swelling and a faster release of ethacridine lactate, lower melting temperature of polymer crystallites, and a decrease in shape fixity ratio of the programmed temporary shape. For unloaded networks, the material behavior in vivo was independent of the mechanical load associated with different implantation sites and agreed well with data from in vitro degradation studies. Thus, AB networks could be used as novel matrices for biofunctional implants, e.g., for urogenital applications, which can self-anchor in vivo and provide mechanical support, release drugs, and finally degrade in the body to excretable fragments.

Shape-memory polymers are of high scientific and technological interest in the biomedical field, e.g., as matrix for self-anchoring implantable devices. In this study, two different star-shaped copolyester tetroles, semi-crystalline oligo[(-caprolactone)-co-glycolide]tetrol (oCG) and amorphous oligo[(rac-lactide)-co-glycolide]tetrol (oLG), were synthesized and subsequently crosslinked by a low molecular weight diisocyanate resulting in copolyester urethane networks (N-CG, N-LG). Both networks could be loaded with model drugs and a diffusion controlled release of the drugs was observed without any effect on the mass loss as measure of hydrolytic degradation. However, the N-CG network’s capability of shape programming was disturbed as the crystallinity of the precursors got lost in the complex three dimensional architecture after crosslinking. By contrast, amorphous N-LG network showed an excellent shape-memory capability with a switching temperature around 36 °C corresponding to their glass transition temperature. This led to triple-functional materials combining biodegradability, shape-memory, and controlled drug release.

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.

Modern concepts for biofunctional implants often comprise the controlled release of bioactive compounds to gain specific biofunctionalities. Here, amorphous and semi-crystalline copolyester-based shape-memory polymer (SMP) networks are reported as matrix for pharmaceutical applications. Drug loading of such crosslinked networks by swelling techniques requires tools to determine the actual payload. In this report, the capability of determining loading kinetics by mass increase or changes of drug concentration in the swelling medium is explored for two types of copolyester-based SMP networks differing in their crosslinking chemistry. Nitrofurantoin and ethacridine lactate served as hydrophobic and hydrophilic model drugs. It was found, that the absolute values of the determined payload did not systematically agree with those obtained by the more reliable technique of network cleavage and spectrophotometric quantification. However, the studies indicate that for both types of SMP materials and both drugs, maximum incorporation of the drugs occurred within a few hours. The time until equilibration depended on the network properties.