Poly(hydroxybutyrate-co-hydroxyvalerate) Porous Matrices from Thermally Induced Phase Separation

Abstract

Thermally induced phase separation followed by freeze drying has been used to prepare biodegradable and biocompatible scaffolds with interconnected 3D microporous structures from poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) copolymers containing 5 and 12 wt % of 3-hydroxyvalerate (HV). Solutions of PHBV in 1,4-dioxane, underwent phase separation by cooling under two different thermal gradients (at −25 °C and −5 °C). The cloud point and crystallization temperature of the polymer solutions were determined by turbidimetry and differential scanning calorimetry, respectively. Parameters affecting the phase separation mechanism such as variation of both the cooling process and the composition of the PHBV copolymer were investigated. Afterwards, the influence of these variables on the morphology of the porous structure and the final mechanical properties (i.e., rigidity and damping) was evaluated via scanning electron microscopy and dynamic mechanical thermal analysis, respectively. While the morphology of the scaffolds was considerably affected by polymer crystallization upon a slow cooling rate, the effect of solvent crystallization was more evident at either high hydroxyvalerate content (i.e., 12 wt % of HV) or high cooling rate. The decrease in the HV content gave rise to scaffolds with greater stiffness because of their higher degree of crystallinity, being also noticeable the greater consistency of the structure attained when the cooling rate was higher. Scaffolds were fully biocompatible supports for cell adhesion and proliferation in 3D cultures and show potential application as a tool for tissue regeneration.

Recent Progress on Biodegradable Tissue Engineering Scaffolds Prepared by Thermally-Induced Phase Separation (TIPS)

“…Nowadays, many variations concerning TIPS methodology have been developed by altering process parameters [ 46 , 51 , 65 ], using different solvents [ 140 ] or combining the process with other technologies. One of these variations is focused to increase the pores size of the scaffold by adding porogen particles, which can be removed from the system after freeze-drying in a subsequent leaching step.…”

“…Many techniques have been developed to produce porous tissue engineering scaffolds, such as porogen leaching [ 36 , 37 ], emulsion freeze drying [ 38 , 39 ], 3D printing [ 40 ], gas foaming [ 41 , 42 ], electrospinning [ 43 , 44 , 45 ], thermally-induced phase separation (TIPS) [ 46 , 47 ] and any possible combinations of two of these techniques [ 48 ].…”

“…Adjusting such parameters, allows for efficient control over the final structure of the scaffold in terms of morphology, average pore size and degree of interconnected pores, which have a significant and very often limiting role in tissue regeneration [ 48 , 51 ]. Additionally, other important features of scaffolds like biodegradability [ 52 ] and mechanical properties [ 46 , 47 ] can also be controlled by the TIPS method. Porous scaffolds of tissue engineering can be prepared by TIPS technique without remnant of solvents, so preserving the biocompatibility of the scaffold [ 50 ].…”

“…This method allows obtaining polymeric foams with porosity over 95% [ 57 ] and pore diameters from ~1 to 100 µm [ 53 ]. Numerous innovations in this area, including combination of TIPS with other fabrication techniques such as electrospinning [ 58 , 59 ], porogen leaching [ 60 , 61 , 62 ], 3D printing [ 21 , 22 , 63 ], modification of the solvent removal procedure [ 14 , 64 ] or variations in TIPS parameters [ 14 , 21 , 46 , 51 , 64 , 65 ] has been reported in literature.…”

“…All these advancements have enabled researchers to produce a variety of architectures and pore morphologies in micro/nanometer scale, desirable for specific utilizations. Porous scaffolds with architectures identified as micro/macro-porous [ 18 , 22 , 66 ], fibrillar (nano/micro-fibrous) [ 13 , 18 , 63 , 67 , 68 ], isotropic (random-pore) [ 46 , 51 , 60 , 69 , 70 ], anisotropic (oriented/aligned-pore or microtubular) [ 62 , 64 , 71 , 72 , 73 , 74 ], bilayered [ 58 , 59 , 75 ], biphasic [ 20 , 75 ] structures, lamellar platelets, lamellar stacks, axialites, spherulites [ 14 ] or a mixture of these structures have recently been produced by TIPS or TIPS-based strategies.…”