Browsing by Author "Prawel, David, advisor"
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Item Open Access A novel approach for critical bone defect repair(Colorado State University. Libraries, 2022) Schneiderhan, Adam, author; Prawel, David, advisor; Popat, Ketul, committee member; Séguin, Bernard, committee memberCritical bone defects are defined as defects that will not naturally heal over a patient's lifetime, even with surgical stabilization. When these occur in the long bones of the axial skeleton (secondary to trauma, tumor resection, etc.), limb-sparing surgery can be performed to avoid amputation of the limb. This procedure typically involves the installation of a steel locking plate over the defect, along with an endoprosthesis or allograft to fill the void of resected bone. Much progress has been made in the natural bone regeneration using tissue engineering (TE) scaffolds in place of these grafts. Porous hydroxyapatite (HAP) is a well-established bone TE scaffold biomaterial but lacks sufficient mechanical strength when fabricated at porosities shown to best induce osteogenesis. To remedy this, polymers such as polycaprolactone (PCL) are often mixed with HAP to fabricate scaffolds with increase load-bearing capacity. However, the addition of PCL makes the scaffold less osteogenic and dramatically slows the degradation rate of the scaffold. This translates into reduced new bone volume where the PCL cannot be remodeled as new bone is formed. This project involves a pilot clinical trial of a novel method that augments the gold-standard limb-sparing procedure by implanting a 3D printed endoprosthetic "sleeve" device that attaches to the locking fixation plate and contains and protects the brittle HAp scaffold. The PCL sleeve alleviates the dependency on scaffold strength which enables use of the most osteogenic possible biomaterials at ideal porosities to maximize the rate and density of new bone formation. The purpose of the study is to clinically validate the construct design and surgical procedure. Thus far, pilot limb-sparing surgeries have been performed on 4 client-owned dogs, in which sleeve-scaffold devices were installed in the critical defects caused by the removal of osteosarcomas in distal epiphyseal radii. Recombinant human bone morphogenic protein-2 (rhBMP-2) was added to the scaffolds to further encourage osteogenesis. Mechanical tests were performed on both the sleeves alone and the full construct installed in canine cadaver limbs. Results from this testing demonstrate the sleeve's ability to prevent mechanical failure of the HAp scaffolds. Similarly, no scaffold failure has been observed in clinical trial patients, with some having the device installed for greater than 24 weeks. Additionally, pressureometry and gait analysis confirmed excellent return of limb function in these animals. However, to date, no new bone formation has been observed within the scaffold devices, which has likely been inhibited by anti-cancer treatment. Regardless, results from ex vivo testing and the clinical trial validate the construct design and the viability of our novel method for protecting and maintaining brittle bone tissue engineering scaffolds, while aiding in restoration of normal limb function.Item Open Access Design, fabrication, and characterization of 3D printed ceramic scaffolds for bone regeneration(Colorado State University. Libraries, 2024) Baumer, Vail Olin, author; Prawel, David, advisor; McGilvray, Kirk, committee member; Heyliger, Paul, committee memberSynthetic bone tissue scaffolds are a promising alternative to current clinical techniques for treating critically large bone defects. Scaffolds provide a three-dimensional (3D) environment that mimics the properties of bone to accelerate bone regeneration. Optimal scaffolds should match the mechanical properties of the implantation site, feature a highly porous network of interconnected channels to facilitate mass transport, and exhibit surface properties for the attachment, proliferation, and differentiation of bone cell lineages. 3D printing has enabled the manufacture of complex scaffold topologies that meet these requirements in a variety of biomaterials which has led to rapidly expanding research. Structural innovations such as triply periodic minimal surfaces (TPMS) are enabling the production of scaffolds that are stiffer and stronger than traditional rectilinear topologies. TPMS are proving to be ideal candidates for bone tissue engineering (BTE) due to their relatively high mechanical energy absorption and robustness, interconnected internal porous structure, scalable unit cell topology, and smooth internal surfaces with relatively high surface area per volume. Among the material options, calcium phosphate-based ceramics, such as hydroxyapatite and tricalcium phosphate, are popular for BTE due to their high levels of bioactivity (osteoconductivity, osteoinductivity and osteointegration), compositional similarities to human bone mineral, non-immunogenicity, tunable degradation rates, and promising drug delivery capabilities. Despite the potential for TPMS ceramic scaffolds in BTE, few studies have explored beyond the popular Gyroid topology. Of the many TPMS options, the Fischer Koch S (FKS) has been simulated to be stronger, be more isotropic, have higher surface area, and absorb more energy than Gyroid at high porosities. In this report, we present a method for photocasting any TPMS in hydroxyapatite which is used to 3D print the first FKS ceramic scaffold. Results indicated that the resolution and accuracy of the process is suitable for BTE, and the custom software for producing the scaffolds was made available to the open-source community. Then, FKS and Gyroid scaffolds were designed to match the properties of trabecular bone using this method for use in critical bone defect repair. The scaffolds were printed and characterized using compressive and flow-based testing to reveal that, while both designs could mimic the low end of natural bone performance, the FKS were 32% stronger and only 11% less permeable than Gyroid. These findings emphasized the need for further characterization of these scaffolds beyond mechanical analysis and into studies of cell growth. To accomplish this, a custom multi-channel perfusion bioreactor was designed to culture cells on these scaffolds to investigate differences in cell behavior with higher efficiency than current designs. The design, capable of culturing many samples simultaneously, was validated using computational fluid dynamics and cell growth assays to demonstrate osteogenic effects and repeatability. In this work, novel TPMS scaffolds were fabricated from hydroxyapatite with sufficient accuracy and quality for large defects, testing of these scaffolds matched trabecular bone performance and suggested that FKS may be superior to Gyroid, and lastly, a four-channel bioreactor system was designed and validated to enable researchers to further characterize scaffolds for BTE.Item Open Access Structural optimization of 3D printed hdyroxyapatite scaffolds(Colorado State University. Libraries, 2021) Isaacson, Nelson D., author; Prawel, David, advisor; James, Susan, committee member; Séguin, Bernard, committee memberPoor healing of critically sized bone defects affects 1.5 million Americans per year and results in more than $1 billion in treatment and therapy cost. Treatment options remain limited and often lead to reoperations, clinical complications, poor functional outcomes, and limb loss, making this one of the biggest challenges in orthopedic medicine, resulting in significant personal and economic cost. Healing strategies using autografts, allografts and xenografts are limited by shortage of available tissue and failure to heal, with complication rates of 50% from delayed or non-union, 30% from allograft fracture, and 15% from infection. Decades of research has been dedicated to solving this problem using a wide variety of bone regeneration techniques. Tissue engineered solutions have emerged that deploy biodegradable, osteoconductive scaffolds to provide structural support and osteoinductive stimulus, with suitable porosity to enable nutrient and waste exchange and angiogenesis. Promising calcium phosphate biomaterials like hydroxyapatite (HAp) and β-tricalcium phosphate are widely studied for bone regeneration scaffolds due to their excellent bioactivity (osteoinductivity, osteoconductivity and osseointegration), mineral composition and tunable degradation rates. Advanced scaffold topologies such as a type of triply periodic minimal surface (TPMS) structure called gyroids are yielding scaffolds that are stiffer and stronger than traditional rectilinear scaffold topologies. Gyroids are ideal candidates for scaffold designs due to their relatively high mechanical energy absorption and robustness, interconnected internal porous structure, scalable unit cell topology, and smooth internal surfaces with relatively high surface area per volume. In our study, a method of layer-wise, photopolymerized viscous extrusion, a type of additive manufacturing, was used to fabricate HAp gyroid scaffolds with 60%, 70% and 80% porosities. Our study is the first to use this method to produce and evaluate calcium-phosphate-based scaffolds. Gyroid topology was selected due to its interconnected porosity and superior, isotropic mechanical properties compared to typical rectilinear lattice structures. Our 3D printed scaffolds were mechanically tested in compression and examined to determine the relationship between porosity, ultimate compressive strength, and fracture behavior. Compressive strength increased with decreasing porosity. Ultimate compressive strengths of the 60% and 70% porous gyroids are comparable to that of human cancellous bone, and higher than previously reported for rectilinear scaffolds of the same material. Our gyroid scaffolds exhibited ultimate compressive strength increases between 1.5 and 6.5 times greater than expected, based on volume of material, as porosity decreased. The Weibull moduli, a measure of failure predictability, were predictive of failure mode and found to be in the accepted range for engineering ceramics. The gyroid scaffolds were also found to be self-reinforcing such that initial failures due to minor manufacturing inconsistencies did not appear to be the primary cause of premature failure of the scaffold. The porous gyroids exhibited scaffold failure characteristics that varied with porosity, ranging from monolithic failure to layer-by-layer failure, and demonstrated self-reinforcement in each porosity tested.