A novel poly­(urethane-urea) (PUU) based on poly­(glycolide-co-ε-caprolactone) macro-diol with tunable mechanical properties and biodegradation behavior is reported for corneal stromal tissue regeneration. Zn–Al layered double hydroxide (LDH) nanoparticles were synthesized and loaded with vitamin C (VC, VC-LDH) and dispersed in the PUU to control VC release in the cell culturing medium. To mimic the corneal stromal EC, scaffolds of the PUU and its nanocomposites with VC-LDH (PUU-LDH and PUU-VC-LDH) were fabricated via electrospinning. Average diameters of the aligned nanofibers were recorded as 325 ± 168, 343 ± 171, and 414 ± 275 nm for the PUU, PUU-LDH, and PUU-VC-LDH scaffolds, respectively. Results of hydrophilicity and mechanical properties measurements showed increased hydrophobicity and reduced tensile strength and elongation at break upon addition of nanoparticles to the PUU scaffold. VC release studies represented that intercalation of the drug in Zn-Al-LDH controlled the burst release and extended the release period from a few hours to 5 days. Viability and proliferation of stromal keratocyte cells on the scaffolds were investigated via AlamarBlue assay. After 24 h, the cells showed similar viability on the scaffolds and the control. After 1 week, the cells showed some degree of proliferation on the scaffolds, with the highest value recorded for PUU-VC-LDH. SEM images of the scaffolds after 24 h and 1 week confirmed good penetration and attachment of keratocytes on all the scaffolds and the cells oriented with the direction of nanofibers. After 1 week, the PUU-VC-LDH scaffold was fully covered by the cells. Immunocytochemistry assay (ICC) was performed to investigate secretion of vimentin protein, ALDH3A1, and α-SMA by the cells. After 24h and 1 week, remarkably higher levels of vimentin and ALDH3A1 and lower level of α-SMA were secreted by keratocytes on PUU-VC-LDH compared to those on the PUU and PUU-LDH scaffolds and the control. Our results suggest that the aligned PUU-VC-LDH is a promising candidate for corneal stromal tissue engineering due to the presence of zinc and vitamin C.

Two series (random and block) poly(glycolide-co-ε-caprolactone) macrodiols with various glycolide to ε-caprolactone ratios (50/50 and 30/70, R-PG50C, R-PG30C, B-PG50C, and B-PG30C) were synthesized. Next, segmented polyurethanes (PUs) were synthesized based on the synthesized macrodiols, 1,6-hexamethylene diisocyanate and 1,4-butanediol (PU-R30, PU-R50, PU-B30, and PU-B50). Effect of glycolide (G) and ε-caprolactone (C) monomers arrangement (random or block) on the PUs properties were investigated via FTIR, 1 H NMR, DSC, TGA, DMA, SEM, and mechanical tests. All PUs illustrated T g (−33°C to −48°C) and T m (102°C to 139°C) corresponding to the soft and the hard segments, respectively. Polymers based on block macrodiols also showed T m related to the soft segments. While PUs underwent a two-step thermal degradation, the PUs based on block macrodiols indicated higher degradation temperature.Dynamic mechanical analysis results evidenced development of a well-defined microphase separated structure in PU-R30. Contact angle (about 70°-80°) and water uptake (around 20% after 24 hours) of the PU films are close to those suitable for tissue engineering materials. The PU based on R-PG30C (PU-R30) exhibited the highest tensile strength (2.87 MPa) followed by PU-B50 and PU-R50. Over a 63-day in vitro degradation study in phosphate buffered saline, the PUs showed variable weight loss (up to 40%) depending on their soft segments composition and arrangement. Also, the PUs showed no cytotoxicity. Thus, these PUs with tunable biodegra- To the best of our knowledge, there are not much reports on systematic synthesis of polyurethanes based on (glycolide-cocaprolactone) macrodiols of different glycolide to caprolactone ratios (as the soft segment), and HDI and butanediol (BD) (as components of the hard segment). Therefore, in this work, PGC macrodiols with different monomer ratios and different comonomers were synthesized and characterized. Then 2 series of SPUs based on these macrodiols and HDI and BD were produced. The effect of macrodiol structure on physicochemical, mechanical properties, and biodegradation rate of the synthesized polymers was investigated. | MATERIALS AND METHODS | MaterialsGlycolide, 1,4-butanediol and tin (II) 2-ethylhexanoate (Sn(Oct)2) were purchased from Sigma_ Aldrich Co, Germany. ε-Caprolactone (>99%), ethylene glycol, 1,6-hexamethylene diisocyanate, 1,2-dichroethane, and n-hexane were obtained from Merck Chemicals, Germany.1,2-Dichroethane and ε-caprolactone were dried prior to use. | Synthesis of PGC macrodiolsRandom and block PGC (R-PGC and B-PGC) macrodiols were synthesized via ring opening polymerization of glycolide and ε-caprolactone initiated by ethylene glycol. In random series, glycolide, ε-caprolactone, ethylene glycol, and the catalyst (stannous octoate)were heated at 130°C under a flow of dry N 2 . After certain time, the reaction mixture was cooled down to room temperature. To remove the catalyst and any residual monomers, the mixture was dissolved in 1.2-dichloroethane, and the copolymer w...