Recent Developments in Cyclic Acetal Biomaterials for Tissue Engineering Applications

Polymer scientists, working closely with those in the device and medical fields, have made tremendous advances over the past 30 years in the use of synthetic materials in the body. In this article we will focus on properties of biodegradable polymers which make them ideally suited for orthopedic applications where a permanent implant is not desired. The materials with the greatest history of use are the poly(lactides) and poly(glycolides), and these will be covered in specific detail. The chemistry of the polymers, including synthesis and degradation, the tailoring of properties by proper synthetic controls such as copolymer composition, special requirements for processing and handling, and mechanisms of biodegradation will be covered. An overview of biocompatibility and approved devices of particular interest in orthopedics are also covered.

Polymer therapeutics encompass polymer-protein conjugates, drug-polymer conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein conjugates with improved stability and pharmacokinetic properties have been developed, for example, by anchoring enzymes or biologically relevant proteins to polyethylene glycol components (PEGylation). Several polymer-protein conjugates have received market approval, for example the PEGylated form of adenosine deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular-weight polymers through a cleavable linker is an effective method for improving the therapeutic index of clinically established agents, and the first candidates have been evaluated in clinical trials, including, N-(2-hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel, and platinum(II) complexes. Another class of polymer therapeutics are drug-delivery systems based on well-defined multivalent and dendritic polymers. These include polyanionic polymers for the inhibition of virus attachment, polycationic complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures for the encapsulation of drugs. In this Review an overview of polymer therapeutics is presented with a focus on concepts and examples that characterize the salient features of the drug-delivery systems.