Minna Malin

Biodegradable lactone copolymers. II. Hydrolytic study of ε-caprolactone and lactide copolymers

Copolymers of e-CL/L-LA and e-CL/DL-LA were allowed to age in a buffer solution of pH 7 at 23 and 37°C. The effects of time and temperature on the rate of hydrolysis were examined by various techniques including weighing (water absorption and weight loss), SEC (molecular weight and polydispersity), and DSC (thermal properties). For comparison, the hydrolytic behavior of PLLA, PDLLA, and commercial PCL homopolymers was investigated by the same methods. SEC measurements showed that molecular weights of the copolymers and PLA homopolymers started to decrease during the first week of hydrolysis, but significant mass losses occurred only much later. As expected, there was no change in either molecular weight or mass of PCL during the hydrolysis study. The kinetic results for copolymers and homopolymers were calculated to study the degradation mechanism. During hydrolysis, the crystallinity of the initially semicrystalline copolymers increased and some crystallinity appeared in the initially amorphous L-LA-containing copolymers.

Biodegradable and bioactive porous scaffold structures prepared using fused deposition modeling

Three-dimensional printing (3DP) refers to a group of additive manufacturing techniques that can be utilized in tissue engineering applications. Fused deposition modeling (FDM) is a 3DP method capable of using common thermoplastic polymers. However, the scope of materials applicable for FDM has not been fully recognized. The purpose of this study was to examine the creation of biodegradable porous scaffold structures using different materials in FDM and to determine the compressive properties and the fibroblast cell response of the structures. To the best of our knowledge, the printability of a poly(ε-caprolactone)/bioactive glass (PCL/BAG) composite and L-lactide/ε-caprolactone 75/25 mol % copolymer (PLC) was demonstrated for the first time. Scanning electron microscope (SEM) images showed BAG particles at the surface of the printed PCL/BAG scaffolds. Compressive testing showed the possibility of altering the compressive stiffness of a scaffold without changing the compressive modulus. Compressive properties were significantly dependent on porosity level and structural geometry. Fibroblast proliferation was significantly higher in polylactide than in PCL or PCL/BAG composite. Optical microscope images and SEM images showed the viability of the cells, which demonstrated the biocompatibility of the structures.

Biodegradable lactone copolymers. III. Mechanical properties of ε-caprolactone and lactide copolymers after hydrolysis in vitro

Copolymers of e-CL/L-LA and e-CL/DL-LA and for comparison homopolymers PLLA, PDLLA, and PCL were allowed to age in a buffer solution of pH 7 at 23 and 37°C and studied for the changes in the mechanical properties taking place as a function of hydrolysis time. Tensile modulus measurements showed the copolymers to retain their modulus much longer than did the PLA homopolymers. The copolymers became stiffer with hydrolysis, while the elongation at break decreased gradually. For the amorphous P(CL60/L-LA40) copolymer, the tensile modulus and yield stress values increased dramatically in hydrolysis. The initial copolymer was soft and tough but became more brittle during hydrolysis, and it exhibited a plasticlike rather than a rubberlike deformation, though the stress values were still very low. After a short period of decrease at the beginning of hydrolysis, the tensile modulus of P(CL80/L-LA20) and P(CL40/L-LA60) copolymers to some extent increased. Yield stress values for these copolymers decreased during hydrolysis. The tensile modulus of PLLA and PDLLA began to decrease during the first days, i.e., the material became weaker. In the case of PCL, the tensile modulus remained almost the same during the 70 days of the test. The degradation was also studied by 13C-NMR. Caproyl homopolymeric sequences did not degrade significantly during hydrolysis.

Novel additive manufactured scaffolds for tissue engineered trachea research

Abstract Conclusions: This study demonstrates proof of concept for controlled manufacturing methods that utilize novel tailored biopolymers (3D photocuring technology) or conventional bioresorbable polymers (fused deposition modeling, FDM) for macroscopic and microscopic geometry control. The manufactured scaffolds could be suitable for tissue engineering research. Objectives: To design novel trachea scaffold prototypes for tissue engineering purposes, and to fabricate them by additive manufacturing. Methods: A commercial 3D model and CT scans of a middle-aged man were obtained for geometrical observations and measurements of human trachea. Model trachea scaffolds with variable wall thickness, interconnected pores, and various degrees of porosity were designed. Photocurable polycaprolactone (PCL) polymer was used with 3D photocuring technology. Thermoplastic polylactide (PLA) and PCL were used with FDM. Cell cultivations were performed for biocompatibility studies. Results: Scaffolds of various sizes and porosities were successfully produced. Both thermoplastic PLA and PCL and photocurable PCL could be used effectively with additive manufacturing technologies to print high-quality tubular porous biodegradable structures. Optical microscopic and SEM images showed the viability of cells. The cells were growing in multiple layers, and biocompatibility of the structures was shown.

PROPERTIES AND POLYMERIZATION OF BIODEGRADABLE THERMOPLASTIC POLY(ESTER-URETHANE)

Abstract Aliphatic polyesters, such as poly(lactic acids), need high molecular weight for acceptable mechanical properties. This can be achieved through ring-opening polymerization of lactides. The lactide route is, however, relatively complicated, and alternative polymerization routes are of interest. In this paper we report the properties of a polymer made by a two-step process: first a condensation polymerization of lactic acid and then an increase of the molecular weight with diisocyanate. The end product is then a thermoplastic poly(ester-urethane). The hydroxylterminated prepolymer was made with condensation polymerization of L–lactic acid and a small amount of 1,4-butanediol. The polymerization was performed in the melt under nitrogen and reduced pressure. The preparation of poly(ester-urethane) was done in the melt using aliphatic diisocyanates as the chain extenders reacting with the end groups of the prepolymer. The polymer samples were carefully characterized, including preliminary degradation ...

Photocrosslinkable Polyesters and Poly(ester anhydride)s for Biomedical Applications

Crosslinking is a feasible way to prepare biodegradable polymers with potential in biomedical applications such as controlled release of active agents and tissue engineering. A synthesis route in which functional telechelic aliphatic polyester oligomers are used as precursors for the preparation of crosslinked polyesters and poly(ester anhydride)s is described. Mechanical properties, degradation characteristics and rate, and bioactivity can be modified widely by controlling the chemical composition and architecture of the crosslinkable oligomers. In tissue engineering, photocrosslinking allows to use crosslinkable oligomers in advanced manufacturing techniques like micromolding in capillaries, stereolithography and two-photon polymerization.

Osteoblast response to continuous phase macroporous scaffolds under static and dynamic culture conditions

Average scaffold pore sizes in the order of several hundred microns are generally required for efficient bone tissue ingrowth in vivo, whereas the culture of large bone engineering constructs in vitro can require bioreactor cultures to decrease diffusional constraints on the cells. In this study, we prepared poly(epsilon-caprolactone/D,L-lactide)-based scaffolds with continuous phase macroporosity using a novel CaCl(2) . 6H(2)O porogen agent. Osteogenic differentiation and scaffold colonization in rat bone marrow stromal cell cultures were compared in such polymer scaffolds, and in composites with 30 wt % bioactive glass filler. The effect of a rotating wall bioreactor culture on the cell response was also evaluated. Bioactive filler enhanced proliferation, early osteogenic differentiation, and mineralization of the cultured cells under static conditions. Dynamic cultures, in turn, resulted in decreased cell numbers and inhibition of the differentiation process irrespective of the scaffold type. This effect was ascribed to the harsh mechanical stresses caused by constant collisions of the scaffolds in the bioreactor vessels. However, cells were able to penetrate into the scaffold interior only under dynamic culture conditions. Thus, interconnected macroporosity is an essential, but not sufficient, condition to allow for full colonization of millimeter scale tissue engineering scaffolds in vitro.

Ectopic bone formation in and soft-tissue response to P(CL/DLLA)/bioactive glass composite scaffolds.

OBJECTIVES To characterize biological response to subcutaneously implanted macroporous poly(ε-caprolactone/D,L-lactide)-based scaffolds, and to evaluate the effect of bioactive glass (BAG) filler and osteogenic cells to the tissue response and ectopic bone formation. MATERIAL AND METHODS In the first part of this study, six different scaffold types were screened in a rat subcutaneous implantation model. The polymer scaffolds with 70/30 caprolactone/lactide ratio and corresponding composites with < 45 μm BAG filler size were chosen for the further ectopic bone formation assay. The scaffolds were loaded with differentiating bone marrow stromal cells and implanted subcutaneously in syngeneic rats. RESULTS With plain scaffolds, only mild foreign body reaction with no signs of gross inflammation was observed after 4 weeks of implantation. Furthermore, the scaffolds were fully invaded by well-vascularized soft connective tissue. Overall, all the tested scaffold types showed an appropriate host response. With cell-seeded scaffolds, several loci of immature mineralizing tissue and small amounts of mature bone were observed after 4 weeks. The incidence of mature bone formation was two and four in polymer scaffolds and composites, respectively (n = 8). After twelve weeks, mature bone was observed in only one polymer scaffold but in seven composites (n = 8). Excluding bone formation, the host response was considered similar to that with cell-free scaffolds. CONCLUSIONS Plain scaffolds supported the ingrowth of well-vascularized fibroconnective tissue. Furthermore, cell seeded composites with BAG filler showed enhanced ectopic bone formation in comparison with corresponding neat polymer scaffolds.

Enhanced osteogenicity of bioactive composites with biomimetic treatment.

Purpose. This study aimed to explore if initiation of biomimetic apatite nucleation can be used to enhance osteoblast response to biodegradable tissue regeneration composite membranes. Materials and Methods. Bioactive thermoplastic composites consisting of poly(ε-caprolactone/DL-lactide) and bioactive glass (BAG) were prepared at different stages of biomimetic calcium phosphate deposition by immersion in simulated body fluid (SBF). The modulation of the BAG dissolution and the osteogenic response of rat mesenchymal stem cells (MSCs) were analyzed. Results. SBF treatment resulted in a gradual calcium phosphate deposition on the composites and decreased BAG reactivity in the subsequent cell cultures. Untreated composites and composites covered by thick calcium phosphate layer (14 days in SBF) expedited MSC mineralization in comparison to neat polymers without BAG, whereas other osteogenic markers—alkaline phosphatase activity, bone sialoprotein, and osteocalcin expression—were initially decreased. In contrast, surfaces with only small calcium phosphate aggregates (five days in SBF) had similar early response than neat polymers but still demonstrated enhanced mineralization. Conclusion. A short biomimetic treatment enhances osteoblast response to bioactive composite membranes.

Elastic Ceramic-Polymer Scaffold with Interconnected Pore Structure: Preparation and In Vitro Reactivity

A series of ceramic-polymer scaffolds were studied for bone tissue engineering applications. These applications require bone reactivity as well as suitable scaffold properties and structure. Bioactive glass (BAG) and sol-gel derived silicas were chosen for ceramic components of the scaffolds, and crosslinked poly(ε-caprolactone/D,L-lactide) copolymers with monomer ratios 90/10 and 70/30 were used as polymer matrices. Scaffolds were prepared by photo-curing crosslinkable oligomers in the presence of the ceramic component and porosity producing salt. Scaffolds with 60-80 vol-% continuous phase macroporosity were obtained by using calcium chloride hexahydrate (CaCl2⋅6H2O), and were further tested in simulated body fluid (SBF). The ceramics remained highly reactive during scaffold preparation resulting in in vitro calcium phosphate formation.