Native tissues possess unparalleled physiochemical and biological functions, which can be attributed to their hybrid polymer composition and intrinsic bioactivity. However, there are also various concerns or limitations over the use of natural materials derived from animals or cadavers, including the potential immunogenicity, pathogen transmission, batch to batch consistence and mismatch in properties for various applications. Therefore, there is an increasing interest in developing degradable hybrid polymer biomaterials with controlled properties for highly efficient biomedical applications. There have been efforts to mimic the extracellular protein structure such as nanofibrous and composite scaffolds, to functionalize scaffold surface for improved cellular interaction, to incorporate controlled biomolecule release capacity to impart biological signaling, and to vary physical properties of scaffolds to regulate cellular behavior. In this review, we highlight the design and synthesis of degradable hybrid polymer biomaterials and focus on recent developments in osteoconductive, elastomeric, photoluminescent and electroactive hybrid polymers. The review further exemplifies their applications for bone tissue regeneration.
|Published (Last):||12 May 2012|
|PDF File Size:||12.38 Mb|
|ePub File Size:||15.84 Mb|
|Price:||Free* [*Free Regsitration Required]|
Review Free to read. Native tissues possess unparalleled physiochemical and biological functions, which can be attributed to their hybrid polymer composition and intrinsic bioactivity.
However, there are also various concerns or limitations over the use of natural materials derived from animals or cadavers, including the potential immunogenicity, pathogen transmission, batch to batch consistence and mismatch in properties for various applications. Therefore, there is an increasing interest in developing degradable hybrid polymer biomaterials with controlled properties for highly efficient biomedical applications.
There have been efforts to mimic the extracellular protein structure such as nanofibrous and composite scaffolds, to functionalize scaffold surface for improved cellular interaction, to incorporate controlled biomolecule release capacity to impart biological signaling, and to vary physical properties of scaffolds to regulate cellular behavior. In this review, we highlight the design and synthesis of degradable hybrid polymer biomaterials and focus on recent developments in osteoconductive, elastomeric, photoluminescent and electroactive hybrid polymers.
The review further exemplifies their applications for bone tissue regeneration. The extracellular matrix ECM of native tissues is composed of a hybrid polymer nanostructure at the molecular level, organized with different biopolymers and nanocrystallites [ 1 ]. Due to their hybrid and well-organized structure, both hard and soft native tissues demonstrate excellent physicochemical properties including viscoelasticity and strength.
They also demonstrate excellent biological activity including cellular biocompatibility and tissue-inductive ability [ 2 ]. Development of new biodegradable biomaterials by mimicking the physicochemical properties and biological activity has therefore gained increasing attention in recent years [ 3 ]. Biomimetic polymer hybrid biomaterials play an important role because they can be synthesized with highly tailored physicochemical properties and bioactivity, through combining different polymers and inorganic phases at the multiple levels [ 4 ].
These polymers have been hybridized in many forms including 3D scaffolds, hydrogels, microspheres, and their composites. In addition to the hybrid structure, osteocondutive property and electroactive ability are also very important for the application of hybrid polymers to regenerate bone [ 18 ].
Regeneration of bone can be accomplished by a combination of osteoinductive materials, regenerative cells and osteogenic growth factors. Local and long-term treatment with bone morphogenetic protein 7 BMP-7 was accomplished by encapsulation of bioactive protein in PLGA microspheres. In combination with a nanofibrous and porous scaffold, treatment with BMP-7 significantly enhanced in vitro osteogenic differentiation and in vivo bone regeneration [ 19 ].
Pure biomedical polymers such as those listed above cannot mimic the mechanical properties of native tissues especially the strength, elasticity and modulus, due to intrinsic shortcomings. Nevertheless, they provide certain advantages. It is possible to use these polymers to design precise micro and nanoscale environments that are beneficial for cell attachment, proliferation and differentiation.
They can also be tailored for tunable drug delivery. Because of these advantages, they are being developed widely for tissue regeneration.
To improve their mechanical and osteogenic properties, bioactive ceramic-based nanophases bioactive glass and calcium phosphate and various polymers natural and synthetic polymers have been hybridized [ 20 — 27 ]. To induce elastomeric behavior, highly elastomeric hybrid polymers were also synthesized through incorporating inorganic phase into biodegradable elastomers [ 28 ].
In particular, siloxane-based biodegradable hybrid polymer elastomers were developed with significantly enhanced mechanical properties and biocompatibility [ 29 — 31 ]. In recent years, electric stimulation has been shown to exhibit a positive effect on tissue regeneration through enhancing cell proliferation and differentiation[ 32 ]. Therefore, conductive components such as carbon-based materials and polymer semiconductors were added to fabricate electroactive hybrid polymer biomaterials for tissue regeneration applications [ 33 ].
This work reviews the design, fabrication, and properties of biodegradable hybrid polymers with a focus on their osteoconductive functions, elastomeric property, and electroactivity. The prospective application of hybrid materials for bone tissue regeneration is also covered in this review. Osteoconductive hybrid polymer biomaterials can be fabricated by incorporating osteoconductive materials into biodegradable polymers.
Biodegradable polymers typically have low elastic modulus and poor osteoconductive activity [ 34 ]. Bioactive inorganic biomaterials including bioactive glass BG and calcium phosphate CP have high conductive activity and bone-bonding ability, and their enhanced potential for bone regeneration have been well described in the literature [ 35 — 39 ].
Therefore, BG and CP-based nanoparticles have been added into various polymers to fabricate osteoconductive hybrid polymers for bone tissue regeneration[ 40 — 43 ]. CP-based polymer hybrid biomaterials have been fabricated successfully by melting, solvent-casting and in situ precipitation [ 44 ].
Most reports showed that addition of low content-CP-based nanoparticles can efficiently improve the mechanical strength and modulus of polymers and improve osteoconductive bioactivity [ 44 ]. Bioactive glass nanoparticles BGN have an amorphous structure and typical chemical composition of SiO 2 -CaO-P 2 O 5 that enable the controlled biodegradation and high bone-bonding activity for in vivo implanting applications [ 45 ].
These hybrid BGN-polymers significantly enhanced compressive strength, tensile strength, elastic modulus, biominerialization, and osteoblast biocompatibility Figure 1. Although BGN-polymer nanocomposites have been developed well in past years, the nanoparticle-based polymer composites still showed uncontrolled biodegradation and mechanical properties in vivo due to the low interface strength between nanoparticles and polymers.
These are known challenges associated with certain BGN-polymer nanocomposites. Bioactive glass particles reinforced PCL osteoconductive hybrid polymers. Reproduced from Ref. Advances have been made in hybrid polymer materials to maintain controlled degradation and mechanical properties while also enhancing in vitro osteoconductive activity [ 49 ].
Gelatin-apatite hybrid nanofibrous scaffolds fabricated by thermally induced phase separation were evaluated for biominerialization in simulated body fluid SBF [ 49 ].
The gelatin-apatite hybrid scaffolds demonstrated significantly enhanced mechanical strength and enhanced expression of osteogenic genes in cells. Additionally, the hybrid scaffold was coated with biological apatite nanocrystals through an electrochemical deposition technology Figure 2 [ 50 ]. The apatite layer thickness could be tailored efficiently by the electrochemical parameters. The deposited hybrid polymer scaffolds also showed enhanced physiochemical properties and osteoconductive activity.
Schematic illustration of a hypothesized mechanism for the growth of calcium phosphate crystals over time. When a deposition voltage is applied, pH in the vicinity of electrode increases, and some calcium phosphate crystals deposited onto the surface of PLLA nanofibers.
Further increase of deposition time leads to the generation of hydrogen bubbles and larger flower-like crystals. Agglomeration of BGNs within the polymer matrix is a challenge associated with hybrid polymers, as these materials may exhibit unfavorable mechanical and physiochemical properties [ 43 ]. To overcome this limitation, silica-based bioactive glass sol SBGS at the molecular level has been used to develop hybrid polymer biomaterials for applications in tissue regeneration.
SBGS reinforced hybrid polymers showed significantly improved mechanical properties including strength, toughness, controlled biodegradation and biominerialization, as well as high osteoblastic activity.
The SBGS-reinforced gelatin hybrid polymer was synthesized through typical sol-gel process, and the interface strength between organic and inorganic phase was controlled by siloxane coupling agents Figure 3. The resulting SBGS-gelatin hybrid showed strong compressive strength, mimicking native bone tissue and providing evidence for its potential application in bone fixation and repair [ 51 ].
SBGS-based gelatin hybrid scaffolds and nanofibrous scaffolds were fabricated through alkaline treatment technology and thermal-induced phase separation Figure 4 — Figure 6. Significantly improved mechanical properties and biocompatibility of SBGS-gelatin hybrids were observed[ 41 , 43 , 51 , 58 — 60 ]. The SBGS-based hybrid polymer biomaterials have shown promise for bone tissue regeneration.
Formation mechanism of the biomimetic siloxane-gelatin SGT hybrid bone implants. Schematic diagram showing an experimental procedure for producing anisotropic porous gelatin-silica hybrid polymer scaffolds by ammonium hydroxide treatment.
Schematic diagram showing an experimental procedure for producing nanofibrous gelatin—silica hybrid scaffolds by the thermally induced phase separation TIPS technique using the mixtures of the gelatin solution and sol—gel derived silica sol. Additional advances have been reported in the use of carbon biomaterial-polymer hybrids as osteoconductive scaffolds for bone regeneration.
Carbon nanomaterials are often synthesized as single sheets, referred to as graphene, or hollow structures referred to as carbon nanotubes CNTs. CNTs can be single-walled or multi-walled, consisting of concentric tubular layers of graphene.
The resulting hybrid scaffold showed suitable mineralization and cytocompatibility in vitro and demonstrated enhanced in vivo bone regeneration capacity in a rat calvarial defect model. Many tissues in the body possess elastomeric properties. Therefore, the development of biomaterials that demonstrate highly elastomeric behavior has garnered much attention. Elastomeric materials are of particular interest because of their biomimetic mechanical properties, which enable their use in the complicated in vivo load environment [ 69 ].
Current biodegradable elastomers include physically crosslinked polymers such as polyurethanes and polyesters, chemically crosslinked polymers such as poly glycerol sebacate PGS and poly citrate diol PCD [ 70 ]. These biodegradable elastomers have shown highly tunable degradation, moderate biocompatibility and good elastomeric mechanical behavior [ 70 ]. They have demonstrated promising applications in regeneration of soft tissue due to their low mechanical strength or poor bioactivity [ 70 ].
To make these elastomers effective for a wider number of biomedical applications, developing hybrid polymers has become an attractive option to obtain biodegradable elastomers with optimized properties to meet different tissue-specific requirements.
The incorporation of PCL significantly enhanced formation of the nanofibrous structure and the hybrid materials showed mechanical properties in the range of human aortic valve tissues [ 71 ]. Gelatin was also added into PGS elastomer to fabricate hybrid polymers for tissue regeneration. The addition of gelatin significantly enhanced the mechanical properties and bioactivity of PGS elastomers [ 72 ].
Although polymer-polymer hybrid elastomers have been well developed, their limited elastomeric behavior and mechanical strength still provent their wide application in bone tissue regeneration. To overcome the limitations of polymer-based elastomers, inorganic phase reinforced hybrid polymer elastomers have been developed in recent years [ 73 — 75 ]. As osteoconductive biomaterials, hydroxyapatite nanoparticles were incorporated into PCD-based elastomers to fabricate composites for orthopedic implants [ 76 ].
Uniform distribution of HA in the polymer matrix significantly enhanced the mechanical properties and osteoconductive biocompatibility of PCD-HA hybrid elastomers. Melt-derived bioglass particles were also introduced into PGS elastomers to improve their range of biomedical applications [ 77 ]. Bioglass particles efficiently enhanced the elastomeric strain and cellular biocompatibility of PGS. These hybrid elastomers still have the intrinsic problem of poor interface intensity between the inorganic phase and polymers.
Therefore, our group introduced bioactive silica into PCD elastomers through a one-step thermal polymerization method [ 30 , 31 , 78 , 79 ]. The inorganic silica phase was bonded with the PCD polymer chain through covalent bonds.
The resulting hybrid polycitrate-silicon PCS elastomers demonstrated significantly improved elastomeric behavior, mechanical strength and cellular biocompatibility Figure 7 [ 30 ]. SBGS-PGS hybrid elastomers exhibited significantly enhanced mechanical properties, biominerialization and cellular biocompatibility Figure 8.
The inorganic phase-grafted PGS and PCD hybrid elastomers have shown promise for applications in bone tissue regeneration. Synthesis of multifunctional silica-poly citrate -based hybrid prepolymers and elastomers. Reproduced from Ref [ 30 ]. Reproduced from Ref [ 29 ] with permission from the Royal Society of Chemistry. Conducting polymers are organic polymers that possess electrical, magnetic and optical properties that are similar to metal, while maintaining desirable mechanical properties as well as ease of processing of polymers [ 80 , 81 ].
Recently, it was found that conductive polymers could tune the properties of cells in electrically sensitive tissues under electrical stimulation, including neural, muscle, cardiac, and bone [ 82 — 84 ].
Regenerative biomaterials for the treatment of bone diseases that need surgical intervention have attracted more attention, particularly with extended life expectancies. Scaffolds that regulate cellular behavior are particularly interesting for such applications [ 85 — 87 ]. A 3-D conductive scaffold that can locally deliver an electrical signal is needed.
Together, these results indicated that these conductive scaffolds exhibited more favorable structural properties for bone repair. The use of conducting polymers loaded with a bioactive molecule has been an emerging approach to functional biomaterial use in tissue regeneration.
Hybrid Polymer Biomaterials for Bone Tissue Regeneration
Hybrid polymer biomaterials for bone tissue regeneration.