Baolin Guo

Synthetic biodegradable functional polymers for tissue engineering: a brief review

Scaffolds play a crucial role in tissue engineering. Biodegradable polymers with great processing flexibility are the predominant scaffolding materials. Synthetic biodegradable polymers with well-defined structure and without immunological concerns associated with naturally derived polymers are widely used in tissue engineering. The synthetic biodegradable polymers that are widely used in tissue engineering, including polyesters, polyanhydrides, polyphosphazenes, polyurethane, and poly (glycerol sebacate) are summarized in this article. New developments in conducting polymers, photoresponsive polymers, amino-acid-based polymers, enzymatically degradable polymers, and peptide-activated polymers are also discussed. In addition to chemical functionalization, the scaffold designs that mimic the nano and micro features of the extracellular matrix (ECM) are presented as well, and composite and nanocomposite scaffolds are also reviewed.

Facile Synthesis of Degradable and Electrically Conductive Polysaccharide Hydrogels

Degradable and electrically conductive polysaccharide hydrogels (DECPHs) have been synthesized by functionalizing polysaccharide with conductive aniline oligomers. DECPHs based on chitosan (CS), aniline tetramer (AT), and glutaraldehyde were obtained by a facile one-pot reaction by using the amine group of CS and AT under mild conditions, which avoids the multistep reactions and tedious purification involved in the synthesis of degradable conductive hydrogels in our previous work. Interestingly, these one-pot hydrogels possess good film-forming properties, electrical conductivity, and a pH-sensitive swelling behavior. The chemical structure and morphology before and after swelling of the hydrogels were verified by FT-IR, NMR, and SEM. The conductivity of the hydrogels was tuned by adjusting the content of AT. The swelling ratio of the hydrogels was altered by the content of tetraaniline and cross-linker. The hydrogels underwent slow degradation in a buffer solution. The hydrogels obtained by this facile approach provide new possibilities in biomedical applications, for example, biodegradable conductive hydrogels, films, and scaffolds for cardiovascular tissue engineering and controlled drug delivery.

Antibacterial and conductive injectable hydrogels based on quaternized chitosan-graft-polyaniline/oxidized dextran for tissue engineering.

Biomaterials with injectability, conductivity and antibacterial effect simultaneously have been rarely reported. Herein, we developed a new series of in situ forming antibacterial conductive degradable hydrogels using quaternized chitosan (QCS) grafted polyaniline with oxidized dextran as crosslinker. The chemical structures, morphologies, electrochemical property, conductivity, swelling ratio, rheological property, in vitro biodegradation and gelation time of hydrogels were characterized. Injectability was verified by in vivo subcutaneous injection on a Sprague Dawley rat. The antibacterial activity of the hydrogels was firstly evaluated employing antibacterial assay using Escherichia coli and Staphylococcus aureus in vitro. The hydrogels containing polyaniline showed enhanced antibacterial activity compared to QCS hydrogel, especially for hydrogels with 3 wt% polyaniline showing 95 kill% and 90kill% for E. coli and S. aureus, respectively. Compared with QCS hydrogel, the hydrogels with 3 wt% polyaniline still showed enhanced antibacterial activity for E. coli in vivo. The adipose-derived mesenchymal stem cells (ADMSCs) were used to evaluate the cytotoxicity of the hydrogels and hydrogels with polyaniline showed better cytocompatibility than QCS hydrogel. The electroactive hydrogels could significantly enhance the proliferation of C2C12 myoblasts compared to QCS hydrogel. This work opens the way to fabricate in situ forming antibacterial and electroactive degradable hydrogels as a new class of bioactive scaffolds for tissue regeneration applications.

Self-Healing Conductive Injectable Hydrogels with Antibacterial Activity as Cell Delivery Carrier for Cardiac Cell Therapy

Cell therapy is a promising strategy to regenerate cardiac tissue for myocardial infarction. Injectable hydrogels with conductivity and self-healing ability are highly desirable as cell delivery vehicles for cardiac regeneration. Here, we developed self-healable conductive injectable hydrogels based on chitosan-graft-aniline tetramer (CS-AT) and dibenzaldehyde-terminated poly(ethylene glycol) (PEG-DA) as cell delivery vehicles for myocardial infarction. Self-healed electroactive hydrogels were obtained after mixing CS-AT and PEG-DA solutions at physiological conditions. Rapid self-healing behavior was investigated by rheometer. Swelling behavior, morphology, mechanical strength, electrochemistry, conductivity, adhesiveness to host tissue and antibacterial property of the injectable hydrogels were fully studied. Conductivity of the hydrogels is ∼10(-3) S·cm(-1), which is quite close to native cardiac tissue. Proliferation of C2C12 myoblasts in the hydrogel showed its good biocompatibility. After injection, viability of C2C12 cells in the hydrogels showed no significant difference with that before injection. Two different cell types were successfully encapsulated in the hydrogels by self-healing effect. Cell delivery profile of C2C12 myoblasts and H9c2 cardiac cells showed a tunable release rate, and in vivo cell retention in the conductive hydrogels was also studied. Subcutaneous injection and in vivo degradation of the hydrogels demonstrated their injectability and biodegradability. Together, these self-healing conductive biodegradable injectable hydrogels are excellent candidates as cell delivery vehicle for cardiac repair.

Nanofiber Yarn/Hydrogel Core-Shell Scaffolds Mimicking Native Skeletal Muscle Tissue for Guiding 3D Myoblast Alignment, Elongation, and Differentiation

Designing scaffolds that can mimic native skeletal muscle tissue and induce 3D cellular alignment and elongated myotube formation remains an ongoing challenge for skeletal muscle tissue engineering. Herein, we present a simple technique to generate core-shell composite scaffolds for mimicking native skeletal muscle structure, which comprise the aligned nanofiber yarn (NFY) core and the photocurable hydrogel shell. The aligned NFYs are prepared by the hybrid composition including poly(caprolactone), silk fibroin, and polyaniline via a developed dry-wet electrospinning method. A series of core-shell column and sheet composite scaffolds are ultimately obtained by encapsulating a piece and layers of aligned NFY cores within the hydrogel shell after photo-cross-linking. C2C12 myoblasts are seeded within the core-shell scaffolds, and the good biocompatibility of these scaffolds and their ability to induce 3D cellular alignment and elongation are successfully demonstrated. Furthermore, the 3D elongated myotube formation within core-shell scaffolds is also performed after long-term cultivation. These data suggest that these core-shell scaffolds combine the aligned NFY core that guides the myoblast alignment and differentiation and the hydrogel shell that provides a suitable 3D environment for nutrition exchange and mechanical protection to perform a great practical application for skeletal muscle regeneration.

Strong Electroactive Biodegradable Shape Memory Polymer Networks Based on Star-Shaped Polylactide and Aniline Trimer for Bone Tissue Engineering

Preparation of functional shape memory polymer (SMP) for tissue engineering remains a challenge. Here the synthesis of strong electroactive shape memory polymer (ESMP) networks based on star-shaped polylactide (PLA) and aniline trimer (AT) is reported. Six-armed PLAs with various chain lengths were chemically cross-linked to synthesize SMP. After addition of an electroactive AT segment into the SMP, ESMP was obtained. The polymers were characterized by (1)H NMR, GPC, FT-IR, CV, DSC, DMA, tensile test, and degradation test. The SMP and ESMP exhibited strong mechanical properties (modulus higher than GPa) and excellent shape memory performance: short recovery time (several seconds), high recovery ratio (over 94%), and high fixity ratio (almost 100%). Moreover, cyclic voltammetry test confirmed the electroactivity of the ESMP. The ESMP significantly enhanced the proliferation of C2C12 cells compared to SMP and linear PLA (control). In addition, the ESMP greatly improved the osteogenic differentiation of C2C12 myoblast cells compared to PH10 and PLA in terms of ALP enzyme activity, immunofluorescence staining, and relative gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). These intelligent SMPs and electroactive SMP with strong mechanical properties, tunable degradability, good electroactivity, biocompatibility, and enhanced osteogenic differentiation of C2C12 cells show great potential for bone regeneration.

Molecular Architecture of Electroactive and Biodegradable Copolymers Composed of Polylactide and Carboxyl-Capped Aniline Trimer

Two-, four-, and six-armed branched copolymers with electroactive and biodegradable properties were synthesized by coupling reactions between poly(l-lactides) (PLLAs) with different architecture and carboxyl-capped aniline trimer (CCAT). The aniline oligomer CCAT was prepared from amino-capped aniline trimer and succinic anhydride. FT-IR, NMR, and SEC analyses confirmed the structure of the branched copolymers. UV-vis spectra and cyclic voltammetry of CCAT and copolymer solution showed good electroactive properties, similar to those of polyaniline. The water contact angle of the PLLAs was the highest, followed by the undoped copolymer and the doped copolymers. The values of doped four-armed copolymers were 54-63 degrees . Thermal properties of the polymers were studied by DSC and TGA. The copolymers had better thermal stability than the pure PLLAs, and the T(g) between 48-58 degrees C and T(m) between 146-177 degrees C of the copolymers were lower than those of the pure PLLA counterparts. This kind of electroactive and biodegradable copolymer has a great potential for applications in cardiovascular or neuronal tissue engineering.

Electroactive porous tubular scaffolds with degradability and non-cytotoxicity for neural tissue regeneration

Electroactive degradable porous tubular scaffolds were fabricated from the blends of polycaprolactone and a hyperbranched degradable conducting copolymer at different feed ratios by a solution-casting/salt-leaching method. Scaning electron microscopy (SEM) and microcomputed tomography tests indicated that these scaffolds had homogeneously distributed interconnected pores on the cross-section and surface. The electrical conductivity of films with the same composition as the scaffolds was between 3.4×10(-6) and 3.1×10(-7) S cm(-1), depending on the ratio of hyperbranched degradable conducting copolymer to polycaprolactone. A hydrophilic surface with a contact angle of water about 30° was achieved by doping the films with (±)-10-camphorsulfonic acid. The mechanical properties of the films were investigated by tensile tests, and the morphology of the films was studied by SEM. The scaffolds were subjected to the WST test (a cell proliferation and cytotoxicity assay using water-soluble tetrazolium salts) with HaCaT keratinocyte cells, and the results show that these scaffolds are non-cytotoxic. These degradable electroactive tubular scaffolds are good candidates for neural tissue engineering application.

Functionalized scaffolds to enhance tissue regeneration

Tissue engineering scaffolds play a vital role in regenerative medicine. It not only provides a temporary 3-dimensional support during tissue repair, but also regulates the cell behavior, such as cell adhesion, proliferation and differentiation. In this review, we summarize the development and trends of functional scaffolding biomaterials including electrically conducting hydrogels and nanocomposites of hydroxyapatite (HA) and bioactive glasses (BGs) with various biodegradable polymers. Furthermore, the progress on the fabrication of biomimetic nanofibrous scaffolds from conducting polymers and composites of HA and BG via electrospinning, deposition and thermally induced phase separation is discussed. Moreover, bioactive molecules and surface properties of scaffolds are very important during tissue repair. Bioactive molecule-releasing scaffolds and antimicrobial surface coatings for biomedical implants and scaffolds are also reviewed.

In situ forming biodegradable electroactive hydrogels

Electroactive injectable degradable hydrogels have great potential as bioactive scaffolds for tissue regeneration. We present the development of a series of in situ forming biodegradable electroactive hydrogels which were synthesized by in situ crosslinking of gelatin-graft-polyaniline (GP) by genipin at body temperature. The chemical structure and electroactivity of the GP co-polymers was confirmed. The formation of in situ hydrogels was demonstrated by the test tube inversion method and rheology measurement. Gelation time, swelling ratio and degradation rate of the hydrogels were controlled by the polyaniline content and genipin content. The conductivity of the hydrogels in the swollen state increased with increasing the polyaniline content in the materials. Interestingly, the hydrogels exhibited a linear release profile of in situ encapsulated diclofenac sodium. The non-cytotoxicity of the hydrogels was confirmed via cell adhesion and proliferation by using bone marrow mesenchymal stem cells and rat C2C12 myoblast cells. These in situ formed degradable electroactive hydrogels represent a new class of biomaterials and as biomimetic scaffolds they have great potential for sophisticated tissue engineering, such as bone, muscle and neural regeneration.