8 Summary, closing remarks and future perspectives
Chapter 7 focused on the potential application of the structures described in
2. Closing remarks and future perspectives
In this thesis, we addressed the limited functionality inherent to synthetic polymeric membranes as applied for GBR procedures. Functionalization
8
techniques were applied to create new materials with improved mechanical properties or which could promote the osteogenic differentiation of pre- osteoblastic cells. Although it was demonstrated that both pre-spinning and post-spinning functionalization strategies enable the production of i) membranes with improved tensile properties, ii) membranes which can be used as drug delivery vehicles iii) micrometric structures functionalized with reactive amine groups, several challenges still need to be addressed, namely the use of non-toxic solvents and the development of more precise approaches when electrospun materials are used as drug delivery systems.
Strong organic solvents are commonly used to dissolve the synthetic polymers prior to electrospinning. This is a major limitation for the definite translation of electrospinning to industry and the scale-up of this technology. The use of organic solvents on an industrial level presents several concerns: i) most organic solvents are highly flammable and volatile, which results in the need to adopt specific safety measures[1] ii) organic solvents are harmful to the environment, and
special measures are needed for their storage and elimination[2] iii) conventional
organic solvents are toxic and not suitable for the dissolution of biomolecules, limiting their use for biomedical applications.[3] New electrospinning
methodologies, denominated as green electrospinning, which focus on more environmentally friendly approaches show promising results. The term green electrospinning is generally used when the dissolution of the polymers and subsequent electrospinning is performed using non-toxic and environmentally friendly solvents, mainly water or aqueous solutions. Water-soluble polymers as poly(ethylene oxide) (PEO), poly(vinyl alcohol) (PVA) or poly(vinylpyrrolidone) (PVP) have been electrospun by this approach.[4] However, water-insoluble
polymers require the use of strong toxic organic solvents, as chloroform, dichloromethane or dimethylformamide. The development of suspension electrospinning and colloidal electrospinning is a recent green electrospinning strategy, where the production of electrospun fibers is based on the dispersion of water-insoluble polymers or copolymers in an aqueous medium.[5, 6] A
second alternative green approach is the electrospinning of thermo-responsive polymers, as poly(N-isopropylacrylamide) (PNIPAM). These polymers are water-soluble below their lower critical solution temperature (LCST), but when electrospun the fibers presented a good stability in aqueous environments.[7]
Room temperature ionic liquids (RTILs) are also gaining increasing attention due to their high conductivity, low vapor pressure, high decomposition temperature and, the capability to chemically modify and recycle the ions.[8] Such properties
make them especially attractive to be used as environmentally friendly solvents for electrospinning. Cellulose fibers have already been produced using RITLs[9]
and efforts are being made to expand the use of ionic liquids for the production of non-cellulosic electrospun fibers.[10, 11]
The sustained delivery of pharmaceutical compounds and biomolecules from electrospun membranes also remains a challenge. The release of pharmaceutical
compounds or biomolecules incorporated in electrospun fibers by blending or coaxial electrospinning is mainly a passive phenomenon, being dependent on the diffusion of the drug or degradation/erosion of the polymeric fibers. On- demand drug delivery systems, where a compound release occurs according to endogenous or exogenous stimuli and on a precise location are considered the next step in the development of drug delivery systems. Temperature, pH or enzyme-cleavable domains can be used to control and direct drug release. Stimuli-based responses can be developed based on the customization and modification of the polymeric backbone or by surface functionalization. Considering the polymeric backbone an interesting approach that should be explored in the future is the development of electrospun fibers based on block-copolymers. Temperature sensitive block-polymers as poly(N-isopropyl acrylamide)[12], poly(N,N-diethylacrylamide)[13], and PEG/PLGA[14] have been
used in the development of temperature-sensitive nanoparticles. PEG-based block copolymers have been used for the development of pH-sensitive delivery systems.[15] Surface functionalization of electrospun fibers is also promising.
Matrix metalloproteinase (MMPs) cleavable domains[16], thermo-responsive
pamidronate[17], or pH-responsive dextran[18] and chitosan[19] have been used
on the surface functionalization of nanoparticles and microparticles and are appealing strategies to be explored for the creation of new on-demand electrospun delivery systems.
In summary, in this thesis electrospinning combined with diverse functionalization techniques were used to develop new biomaterials with improved functional properties for GBR applications and bone tissue engineering. Diverse pre- and post-spinning strategies have led to the development of membranes with improved tensile properties which can potentially be used on GBR applications, and the development of new micrometric structures to be used for drug delivery purposes or as building blocks of new biomaterials. Electrospinning has all the potential to be an important technique in the development of the next generation of biomaterials. For that to occur i) low-cost and environmentally friendly electrospinning methodologies should be explored ii) stimuli-based drug delivery systems should be further investigated.
8
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