RESEARCH NEWS

December 200426

Getting control over functionality

There is growing demand for new

porous materials for medical

applications. Despite recent

technological advances, thousands of

patients die each year while waiting for

organ transplants because of the lack

of donor organs or efficient organ

substitutes. Tissue engineering, which

involves the use of cells to regenerate

damaged tissue and restore function, is

being actively pursued to address this

problem.

For cells to maintain their tissue-

specific functions after being implanted,

a substrate material, usually an organic

polymer, must be inserted to assist the

organization of the cells in three

dimensions. These materials must

exhibit good biocompatibility so that the

implant is not rejected by the body’s

immune system. In addition, the

mechanical properties of the polymer

scaffold must be sufficient to withstand

the patient’s normal activities without

collapse. These materials must also be

easy to sterilize to prevent infection.

Finally, and perhaps most crucially, the

polymer scaffold must have a large

surface area to allow strong cell

attachment and promote tissue growth.

Several methods have been developed

to create highly porous scaffolds,

including fiber bonding, solvent

casting/particulate leaching, gas

foaming, and phase separation. Using

bulk radical copolymerization of

2-hydroxyethyl methacrylate (HEMA)

and ethylene dimethacrylate (EDMA) in

the presence of cyclohexanol,

dodecan-1-ol, or saccharose,

researchers from the Institute of

Macromolecular Chemistry at the

Academy of Sciences of the Czech

Republic report the preparation of

highly porous slabs of poly(2-

hydroxyethyl methacrylate) (PHEMA)

[Hradil and Horák, React. Funct. Polym.

(2004), doi:10.1016/

j.reactfunctpolym.2004.08.007).

The cyclohexanol, dodecan-1-ol, or

saccharose function as porogens,

thermally labile materials that are

removed from the bulk copolymer to

leave the highly porous structure

needed for the implant. Mercury

porosimetry provides information on

both the polymer macroporosity (pores

50 nm to 1 µm in size) and

superporosity (pores greater than

1 µm in size) in the dry state. Most of

the pores in the prepared slabs are in

the macroporous size range. Low

values of the apparent density of the

investigated polymers indicates the

presence of closed pore structures.

Closed pores are undesirable because

cells cannot penetrate.

The porous structure and morphology

of the polymers appears to be affected

by two factors: phase separation during

polymerization and microsphere

aggregation and hydrogel contraction

during polymer drying. Even at low

cross-linker concentrations, the

presence of the porogen in the

polymerization mixture promotes pore

formation. Saccharose in particular

promotes the formation of a large

number of pores.

John K. Borchardt

Porous structures for tissue engineering

Reactive copolymers containing multiple functional groups onthe sidechains attached to the polymer backbone can be usedto prepare multifunctional polymers. These are usuallysynthesized from copolymerization of a hydrophilic orhydrophobic (depending on the end use) basic monomer with areactive monomer. Using a controlled radical polymerizationtechnique to synthesize these materials would provide controlover polymer chain endgroup composition and the ability tosynthesize block copolymers. This flexibility would mean thatpolymers could be synthesized for a variety of specific uses.Marie-Thérèse Charreyre and coworkers at the École NormaleSupérieure de Lyon in France have accomplished this usingthe reversible addition-fragmentation chain transfer (RAFT)polymerization process [Favier et al., Polymer (2004) 45(23), 7821]. The researchers synthesized well-defined N-acryloxysuccinimide (NAS)-based copolymers, which areuseful reactive building blocks to prepare copolymers forbiomedical applications. Using RAFT copolymerization, theycopolymerized NAS and N-acryloylmorpholine (NAM). TheRAFT process provides excellent control of the polymerizationprocess permitting high monomer conversion (>95%) andproducing molecular weights up to 80 000 g/mol with verynarrow molecular weight distributions. The researchersobtained an azeotropic composition (60/40 NAM/NAS molar

ratio) with completely random distribution of the twomonomers. The relative reactivity of NAM and NAS aresimilar in RAFT and conventional copolymerization.The RAFT process also provides efficient control over thefunctionality at the ends of the polymer chains enabling thecopolymer to be incorporated as a block in more complexpolymers. For example, the NAS units provide reactive sitesthat enable poly(NAM-co-NAS) copolymer chains to beintegrated into more complex polymers. Many differentreaction conditions can be used for these subsequentcopolymerizations because poly(NAM-co-NAS) is soluble inboth a wide variety of organic solvents and in aqueous media.For example, block copolymers of poly[(NAM-co-NAS)-b-NAM]with a variable length poly(NAM) block were synthesized withefficient control over the length of the poly(NAM) block andthe poly[(NAM-co-NAS)-b-NAM] molecular weight, molecularweight distribution and polymer composition. The percentage and nature of the reactants with poly(NAM-co-NAS) can also be varied. The NAM units act as spacersbetween the reactive NAS units to enable binding of specificspecies such as bulky polymer grafts, DNA fragments, orproteins. The poly(NAM-co-NAS) chains have already beenused to graft glycopolymer side chains and to bind nucleotidestarters for in situ synthesis of DNA sequences. John K. Borchardt

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