Effect of Molecular Weight and Functionality on Acrylated Poly(caprolactone) for Stereolithography and Biomedical Applications

Abstract

Degradable polymers are integral components in many biomedical polymer applications. The ability of these materials to decompose in situ has become a critical component for tissue engineering, allowing scaffolds to guide cell and tissue growth while facilitating gradual regeneration of native tissue. The objective of this work is to understand the role of prepolymer molecular weight and functionality of photocurable poly(caprolactone) (PCL) in determining reaction kinetics, mechanical properties, polymer degradation, biocompatibility, and suitability for stereolithography. PCL, a degradable polymer used in a number of biomedical applications, was functionalized with acrylate groups to enable photopolymerization and three-dimensional printing via stereolithography. PCL prepolymers with different molecular weights and functionalities were studied to understand the role of molecular structure in reaction kinetics, mechanical properties, and degradation rates. The mechanical properties of photocured PCL were dependent on cross-link density and directly related to the molecular weight and functionality of the prepolymers. High-molecular weight, low-functionality PCLDA prepolymers exhibited a lower modulus and a higher strain at break, while low-molecular weight, high-functionality PCLTA prepolymers exhibited a lower strain at break and a higher modulus. Additionally, degradation profiles of cross-linked PCL followed a similar trend, with low cross-link density leading to degradation times up to 2.5 times shorter than those of more highly cross-linked polymers. Furthermore, photopolymerized PCL showed biocompatibility both in vitro and in vivo, causing no observed detrimental effects on seeded murine-induced pluripotent stem cells or when implanted into pig retinas. Finally, the ability to create three-dimensional PCL structures is shown by fabrication of simple structures using digital light projection stereolithography. Low-molecular weight, high-functionality PCLTA prepolymers printed objects with feature sizes near the hardware resolution limit of 50 μm. This work lays the foundation for future work in fabricating microscale PCL structures for a wide range of tissue regeneration applications.

Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

“…The functionality and subsequent degree of cross-linking has a more significant effect on biodegradation. Up to 2.5 times slower degradation has been observed for highly cross-linked PCL compared to loosely cross-linked structures [84]. Similarly, the polymer ratio PLA/PCL was found to affect biodegradation rates [87].…”

“…FDM fabricated feature sizes of~160 µm were reported [79], while bioprinted PCL structures with feature sizes of~200 µm were produced highlighting how process parameters can affect the morphology of the extruded PCL [80,81,83]. Concerning light-assisted fabrication, PCL structures with resolution down to 50 µm via DLP has been achieved [84]. TPP was used to decrease the feature size even further, down to 1 µm for 3D structures [85].…”

“…The mechanical behavior of structures fabricated by photopolymerization can be adapted by changing the molecular weight and functionality of the prepolymers. For example, low molecular weight (300 g/mol) prepolymer of PCL triol leads to a higher tensile modulus of 6.9 MPa and a low strain of 13% at break [84,86] compared to the high molecular weight (1250 g/mol) PCL diol, which leads to a tensile modulus of 3.3 MPa and 39% strain at break. Also, the ratio of polymers can be reformed to control mechanical properties.…”

Polycaprolactone usage in additive manufacturing strategies for tissue engineering applications: A review

“…To allow photopolymerization, PCL has been modified with acrylates, 36–40 methacrylates, 41,42 and fumarates 43 . But only few studies have reported the use of photocrosslinkable PCL in SLA 36,42 …”

Optimizing Donor Cellular Dissociation and Subretinal Injection Parameters for Stem Cell-Based Treatments

“…The observations in recent reports have demonstrated that photoreceptor precursor cells directly isolated from developing mouse retina and transplanted into diseased hosts results in extensive donor cell death with transfer of donor cell material to remaining host photoreceptor cells, further suggesting that stem cell‐derived progeny are fragile and will be more successfully transplanted on a prefabricated biomimetic graft rather than as a cellular slurry. By dissociating cells during early retinal differentiation and seeding them onto a cell delivery scaffold where they will be allowed to mature and adhere prior to transplantation, one can mitigate acute cellular dissociation effects and maximize post‐transplant cell viability. Moreover, although retinal graft transplantation is our ultimate goal, early stage clinical trials designed to evaluate both safety and efficacy of intravitreal and subretinal injection of a suspension of human RPCs in patients are currently underway (https://clinicaltrials.gov/ numbers NCT02464436 and NCT03073733).…”