Biomedical polymers crosslinked polymer

Nanogels are nanometer-sized hydrogel nanoparticles (less than about 100 nm) with three-dimensional networks of physically crosslinked polymer chains. They have attracted growing interest over the last decade because of their potential for applications in biomedical fields, such as DDS and bioimaging [246-249]. 

Various a-methylenemacrolides were enzymatically polymerized to polyesters having polymerizable methacrylic methylene groups in the main chain (Fig. 3, left). The free-radical polymerization of these materials produced crosslinked polymer gels [10, 12]. A different chemoenzymatic approach to crosslinked polymers was recently introduced by van der Meulen et al. for novel biomedical materials [11]. Unsaturated macrolactones like globalide and ambrettolide were polymerized by enzymatic ROP. The clear advantage of the enzymatic process is that polymerizations of macrolactones occur very fast as compared to the chemically catalyzed reactions [13]. Thermal crosslinking of the unsaturated polymers in the melt yielded insoluble and fully amorphous materials (Fig. 3, right). 

This contribution will provide a review of polylectrolytes as biomaterials, with emphasis on recent developments. The first section will provide an overview of methods of synthesizing polyelectrolytes in the structures that are most commonly employed for biomedical applications linear polymers, crosslinked networks, and polymer grafts. In the remaining sections, the salient features of polyelectrolyte thermodynamics and the applications of polyelectrolytes for dental adhesives and restoratives, controlled release devices, polymeric drugs, prodrugs, or adjuvants, and biocompatibilizers will be discussed. These topics have been reviewed in the past, therefore previous reviews are cited and only the recent developments are considered here. 

In this class of amorphous polymers, there are many biomedical polymers such as phenolic resins (adopted for production of surgical instruments), unsaturated polyester resins (used in bone repair) (Kharas et al., 1997), polystyrene (e.g. Petri dishes for cell culture) and polymethyl methacrylate (PMMA, used in bone cements, intraocular lens, and dental fillings) (Stuart, 2002). These are highly crosslinked polymers (resins in particular) or linear thermoplastic polymers that do not show structural macromolecular regularity. 

The development of fumarate-based polyesters for biomedical applications started around 20 years ago. Fumaric acid is a natural metabolite involved in Krebs cycle, and is comprised of a reactive double bond available for chemically crosslinking reactions. These characteristics make fumaric acid a candidate building block for crosslinkable polymers. The first and most comprehensively investigated fumarate-based copolymer is the biodegradable copolyester poly(propylene fumarate) (PPF) (Fig. 6.8). ... 

Unless a carrier conjugate can fulfill the prerequisities listed under (1), (2) and (3), its usefulness is severely limited. Only when a carrier meets requirements (l)- 3) is it necessary to consider the clinical implications of (4) and (5). Fig. 4 illustrates the basic requirements of the polymeric carrier and the characteristic of both a linear and crosslinked polymer. In the following section examples of soluble synthetic polymers specifically synthesized with respect to biomedical applications are given and the importance of their properties relative to polymeric drug carriers is discussed. 

C. Additional References on Radiation Crosslinked Polymers for Biomedical Applications... 

Polyoxyethylenes, poly(ethylene glycol) with less than 20,000 PEG, are obtained from the polymerization of oxirane and are described in another chapter. They received increasing interest as biomedical polymers due to their bio-/blood compatibility in linear, grafted, and crosslinked gel forms [78-88]. PEGs have been functionalized with various terminals for chemical modifications, (7) [51,89]. 

Finally, a new water-soluble polyphosphazene was recently synthesized that has the structure shown in 36 (46). This polymer has two attributes as a biomedical macromolecule. First, the pendent carboxylic acid groups are potential sites for condensation reactions with amines, alcohols, phenols, or other carboxylic acid units to generate amide, ester, or anhydride links to polypeptides or bioactive small molecules. Second, polymer forms ionic crosslinks when brought into contact with di- or trivalent cations such as Ca or Ai3+. The crosslinking process converts the water-soluble polymer to a hydrogel, a process that can be reversed when the system... 

Some polymer materials, particularly biomedical materials and step-growth polymers, comprise crosslinked networks. The effect of irradiation on networks, compared with linear polymers, will depend on whether scission or crosslinking predominates. Crosslinking will cause embrittlement at lower doses, whereas scission will lead progressively to breakdown of the network and formation of small, linear molecules. The rigidity of the network, i.e. whether in the glassy or rubbery state (networks are not normally crystalline), will affect the ease of crosslinking and scission.. ... 

Polyvinyl alcohol (PVA), which is a water soluble polyhidroxy polymer, is one of the widely used synthetic polymers for a variety of medical applications [197] because of easy preparation, excellent chemical resistance, and physical properties. [198] But it has poor stability in water because of its highly hydrophilic character. Therefore, to overcome this problem PVA should be insolubilized by copolymerization [43], grafting [199], crosslinking [200], and blending [201], These processes may lead a decrease in the hydrophilic character of PVA. Because of this reason these processes should be carried out in the presence of hydrophilic polymers. Polyfyinyl pyrrolidone), PVP, is one of the hydrophilic, biocompatible polymer and it is used in many biomedical applications [202] and separation processes to increase the hydrophilic character of the blended polymeric materials [203,204], An important factor in the development of new materials based on polymeric blends is the miscibility between the polymers in the mixture, because the degree of miscibility is directly related to the final properties of polymeric blends [205],... 

HPMA copolymers are water-soluble biocompatible polymers, widely used in anticancer drug delivery (reviewed in Reference [22]). HPMA copolymers containing reactive groups at side-chain termini were previously used for the modification of trypsin [23], chymotrypsin [23,24], and acetylcholinesterase [25]. The modification dramatically increased the acetylcholinesterase survival in the blood stream of mice and the thermostability of modified enzymes when compared to the native proteins. However, the modification involved multipoint attachment of the copolymers to the substrates, which may cause crosslinking. To modify proteins or biomedical surfaces by one point attachment, semitelechelic polymers should be used. 

Many polymer-polymer complexes can be obtained by template polymerization. Applications of polyelectrolyte complexes are in membranes, battery separators, biomedical materials, etc. It can be predicted that the potential application of template polymerization products is in obtaining membranes with a better ordered structure than it is possible to obtain by mixing the components. The examples of such membranes from crosslinked polyCethylene glycol) and polyCacrylic acid) were described by Nishi and Kotaka. The membranes can be used as so-called chemical valves for medical applications. The membranes are permeable or impermeable for bioactive substances, depending on pH. 

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