3D Printed Biodegradable And Shape Memory Polymer Poly(Glycerol Dodecanedioate) (PGD) For Soft Tissue Reconstruction
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Akman, Ryan
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Abstract
There is an increasing need for the development of biodegradable SMPs, and bioinks for 3D printing, due to the challenges associated with soft tissue repair in the clinic. Specifically, soft tissue repair treatments are challenged by the need for materials that emulate soft tissue mechanical behavior, can be deployed via MIS, and are biodegradable. MIS procedures are becoming more common in the clinic due to their ability to shorten length of hospitalization, reduce complications, and lower operational costs. Utilizing structural repair devices via MIS procedures is challenging due to the small incisions and access profiles created, which can impact the structural integrity of the materials during delivery. Thermally responsive shape memory materials having rigid linear elastic properties during delivery that can fit through these small profiles and expand and fill the defect upon heating to body temperature are advantageous. The use of biodegradable materials for soft tissue repair is desirable as they remove both the need for revision surgeries and the longer term risks associated with permanent implants like erosion and deleterious degradation byproducts. Leveraging advances in 3D printing, SMPs can be manufactured into patient specific medical devices that are a better fit for individual patient needs, while also allowing for low volume production that is not viable using traditional manufacturing methods. The overall goal of this thesis was to develop photocurable SMP resins,
which could be used to 3D print patient specific medical devices without causing a significant inflammatory response in vivo.
The first aim of this work was dedicated to the development of photocurable PGD. Through the use of acrylation chemistry we successfully developed APGD, a chemically crosslinked photocurable SMP. We demonstrate control over the material properties of APGD via adjustments in the acrylation percent of the APGD networks; specifically, we saw that the acrylation percent of APGD directly correlated with changes in the crosslink density of the APGD networks which led to subsequent changes in APGD Tm, ΔHfusion, contact angle measurements, swelling ratio and gel content, hydrolytic degradation, and shape memory behavior. We tested LMW and HMW APGD networks, demonstrating that these material properties were also dependent on APGD molecular weight. Neither acrylation percent nor molecular weight changes caused significant differences in the mechanics of APGD materials tested in uniaxial tension at 37°C. The in vitro biocompatibility of these APGD materials were tested via cytotoxicity, cell proliferation, and cell attachment assays. We found that both acrylation percent and molecular weight effect APGD cytotoxicity and the ability for cells to attach and proliferate on APGD materials in vitro. Assessing these data, it was determined that the HMW APGD showed optimal material properties for in vivo application, including the best in vitro biocompatibility, leading to the use of HMW APGD for the remainder of this work.
Following the development of the photocurable APGD resins, we created a new range of resins with varying acrylation percent, PI concentration, and PI used. Using real time UV curing rheometry assessments, we were able to capture how these variable affect APGD viscosity, gel time, and storage moduli. These data were then used to choose an appropriate resin to 3D print for the remainder of this work. Specifically, 18% APGD with .5wt% PI was chosen for 3D
printing. In addition, these rheometry data provided insight into appropriate 3D printing parameters to use in the 3D printing process. This APGD resin was then 3D printed on both E and DLP printers and the material properties of these samples were measured to determine whether manufacturing modality significantly affected the resultant behavior of the printed samples. LC controls were used to determine whether the layer by layer manufacture of 3D printing played a role in how these APGD materials behaved. Manufacture modality played a clear role in shaping the material properties of these APGD samples. Manufacture modality also influenced the quality of the printed samples and the potential complexity of the designs that could be produced. Ultimately, we were able to show that APGD resin could be used to 3D print complex anatomical structures, demonstrating the potential of this material for clinical translation.
The last part of this work was dedicated to understanding how the different manufacturing modalities affect the degradation, Tm, and chemistry of APGD. Through both in vitro (hydrolytic and enzymatic) and in vivo degradation assays we show clear differences between APGD samples due to manufacture modality. These data also document the similarities and differences exhibited between samples subjected to hydrolytic and enzymatic in vitro degradation versus in vivo degradation conducted via subcutaneous implantation in a mouse. Importantly we are also able to show that APGD samples tested in vivo did not cause significant inflammation or tissue necrosis, which is an important first step in establishing the safety of APGD for use in the clinic.
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Date
2022-08-24
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Dissertation