NANOFIBROUS COMPOSITE SCAFFOLDS OF POLY (ESTER AMIDES) WITH TUNABLE PHYSICOCHEMICAL AND DEGRADATION PROPERTIES

Polymeric elastomers like Poly (1,3-diamino-2-hydroxypropane-co-polyol sebacate) (APS) have gained importance in soft tissue engineering applications due to their tunable mechanical properties and biodegradability. The fabrication of extracellular matrix (ECM)-mimetic nanofibrous scaffolds using APS is however limited due to its poor solubility in commonly used solvents, low viscosity and high temperatures required for thermal curing. In this study, we have overcome these limitations of APS by blending un-crosslinked APS pre-polymer with polycaprolactone (PCL), and have successfully fabricated ECM-mimetic nanofibrous APS scaffolds for the first time. The developed fibrous scaffolds were further characterized for their physicochemical, thermal, mechanical and degradation properties. Effects of APS:PCL weight ratios (0:1, 1:1, 2:1 and 4:1) and total polymer concentration (15-30% w/v) on the fiber morphology, tensile properties, chemical and thermal properties of the APS-PCL composite scaffolds were investigated. Higher APS concentrations in the polymer blend resulted in formation of fused fibers and thus, increased fiber diameters. The degree of hydration and consequently, degradation rate of the scaffolds increased with the APS concentration. The FTIR and DSC studies showed selective loss of APS polymer from composite scaffolds after degradation. Scaffolds with 1:1 APS:PCL ratio exhibited maximum elastic modulus (EM) of 30 ± 2.5 MPa compared to 0:1, 2:1 and 4:1 ratios. Increasing total polymer concentrations (15-30% w/v) at constant (2:1) APS:PCL ratio increased stiffness and tensile strength of the electrospun NANOFIBROUS COMPOSITE SCAFFOLDS OF POLY(ESTER AMIDES) WITH TUNABLE PHYSICOCHEMICAL AND DEGRADATION PROPERTIES FNU Shilpaa Mukundan, M.S. University of Pittsburgh, 2015 v scaffolds. Biocompatibility studies using C2C12 mouse myoblast cells showed enhanced cell spreading on APS containing scaffolds after 6h as compared to PCL-only scaffolds. Thus, the present study demonstrates successful development of APS-based thermoset elastomeric nanofibrous scaffolds by blending with semicrystalline PCL polymer for the first time. Tunable physicochemical, mechanical and degradation properties of these composite APS-PCL scaffolds will be further exploited for skeletal muscle tissue engineering applications. Keywords Poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)(APS); Polycaprolactone (PCL), myoblasts, electrospinning, nanofibrous scaffold

Carbon-Based Hierarchical Scaffolds for Myoblast Differentiation: Synergy between Nano-Functionalization and Alignment

While several scaffolds have been proposed for skeletal muscle regeneration, multiscale hierarchical scaffolds with the complexity of extracellular matrix (ECM) haven’t been engineered successfully. By precise control over nano- and microscale features, comprehensive understanding of the effect of multiple factors on skeletal muscle regeneration can be derived. In this study, we engineered carbon-based scaffolds with hierarchical nano- and microscale architecture with controlled physico-chemical properties. More specifically, we built multiscale hierarchy by growing carbon nanotube (CNT) carpets on two types of scaffolds, namely, interconnected microporous carbon foams and aligned carbon fiber mats. Nanostructured CNT carpets offered fine control over nano-roughness and wettability facilitating myoblast adhesion, growth and differentiation into myocytes. However, microporous foam architecture failed to promote their fusion into multinucleated myotubes. On the other hand, aligned fibrous architecture stimulated formation of multinucleated myotubes. Most importantly, nanostructured CNT carpets interfaced with microscale aligned fibrous architecture significantly enhanced myocyte fusion into multinucleated mature myotubes highlighting synergy between nanoscale surface features and micro-/macroscale aligned fibrous architecture in the process of myogenesis

Carbon-Based Hierarchical Scaffolds for Myoblast Differentiation: Synergy between Nano-Functionalization and Alignment

While several scaffolds have been proposed for skeletal muscle regeneration, multiscale hierarchical scaffolds with the complexity of extracellular matrix (ECM) haven’t been engineered successfully. By precise control over nano- and microscale features, comprehensive understanding of the effect of multiple factors on skeletal muscle regeneration can be derived. In this study, we engineered carbon-based scaffolds with hierarchical nano- and microscale architecture with controlled physico-chemical properties. More specifically, we built multiscale hierarchy by growing carbon nanotube (CNT) carpets on two types of scaffolds, namely, interconnected microporous carbon foams and aligned carbon fiber mats. Nanostructured CNT carpets offered fine control over nano-roughness and wettability facilitating myoblast adhesion, growth and differentiation into myocytes. However, microporous foam architecture failed to promote their fusion into multinucleated myotubes. On the other hand, aligned fibrous architecture stimulated formation of multinucleated myotubes. Most importantly, nanostructured CNT carpets interfaced with microscale aligned fibrous architecture significantly enhanced myocyte fusion into multinucleated mature myotubes highlighting synergy between nanoscale surface features and micro-/macroscale aligned fibrous architecture in the process of myogenesis

Hyperbranched polyester hydrogels with controlled drug release and cell adhesion properties

Hyperbranched polyesters (HPE) have a high efficiency to encapsulate bioactive agents, including drugs, genes and proteins, due to their globe-like nanostructure. However, the use of these highly branched polymeric systems for tissue engineering applications has not been broadly investigated. Here, we report synthesis and characterization of photocrosslinkable HPE hydrogels with sustained drug release characteristics for cellular therapies. These HPE can encapsulate hydrophobic drug molecules within the HPE cavities, due to the presence of hydrophobic inner structure that is otherwise difficult to achieve in conventional hydrogels. The functionalization of HPE with photocrosslinkable acrylate moieties renders the formation of hydrogels with highly porous interconnected structure, and mechanically tough network. The compressive modulus of HPE hydrogels was tunable by changing the crosslinking density. The feasibility of using these HPE networks for cellular therapies was investigated by evaluating cell adhesion, spreading and proliferation on hydrogel surface. Highly crosslinked and mechanically stiff HPE hydrogels have higher cell adhesion, spreading, proliferation compared to soft and complaint HPE hydrogels. Overall, we showed that hydrogels made from HPE could be used for biomedical applications that require control cell adhesion and control release of hydrophobic clues

Hyperbranched Polyester Hydrogels with Controlled Drug Release and Cell Adhesion Properties

Hyperbranched polyesters (HPE) have a high efficiency to encapsulate bioactive agents, including drugs, genes, and proteins, due to their globe-like nanostructure. However, the use of these highly branched polymeric systems for tissue engineering applications has not been broadly investigated. Here, we report synthesis and characterization of photocrosslinkable HPE hydrogels with sustained drug release characteristics for cellular therapies. These HPE can encapsulate hydrophobic drug molecules within the HPE cavities due to the presence of a hydrophobic inner structure that is otherwise difficult to achieve in conventional hydrogels. The functionalization of HPE with photocrosslinkable acrylate moieties renders the formation of hydrogels with a highly porous interconnected structure and mechanically tough network. The compressive modulus of HPE hydrogels was tunable by changing the crosslinking density. The feasibility of using these HPE networks for cellular therapies was investigated by evaluating cell adhesion, spreading, and proliferation on hydrogel surface. Highly crosslinked and mechanically stiff HPE hydrogels have higher cell adhesion, spreading, and proliferation compared to soft and complaint HPE hydrogels. Overall, we showed that hydrogels made from HPE could be used for biomedical applications that require spatial control of cell adhesion and controlled release of hydrophobic clues

Highly elastomeric poly(glycerol sebacate)-co-poly(ethylene glycol) amphiphilic block copolymers

Poly(glycerol sebacate) (PGS), a tough elastomer, has been proposed for tissue engineering applications due to its desired mechanical properties, biocompatibility and controlled degradation. Despite inter- esting physical and chemical properties, PGS shows limited water uptake capacity (w2%), thus con- straining its utility for soft tissue engineering. Therefore, a modification of PGS that would mimic the water uptake and water retention characteristics of natural extracellular matrix is beneficial for enhancing its utility for biomedical applications. Here, we report the synthesis and characterization of highly elastomeric poly(glycerol sebacate)-co-polyethylene glycol (PGS-co-PEG) block copolymers with controlled water uptake characteristics. By tailoring the water uptake property, it is possible to engineer scaffolds with customized degradation and mechanical properties. The addition of PEG results in almost 15-fold increase in water uptake capacity of PGS, and improves its mechanical stability under dynamic loading conditions. PGS-co-PEG polymers show elastomeric properties and can be subjected to serve deformation such as bending and stretching. The Young's modulus of PGS-co-PEG can be tuned from 13 kPa to 2.2 MPa by altering the amount of PEG within the copolymer network. Compared to PGS, more than six-fold increase in elongation was observed upon PEG incorporation. In addition, the rate of degradation increases with an increase in PEG concentration, indicating that degradation rate of PGS can be regulated. PGS-co-PEG polymers also support cell proliferation, and thus can be used for a range of tissue engineering application