MS, University of Cincinnati, 2002, Engineering : Aerospace Engineering

Previous work performed in Noyes-Giannetras Laboratory has shown that mechanical alignment of undifferentiated mesenchymal stem cells about a suture causes alignment of cells and contraction of constructs in culture in a form that is suitable for implantation for tendon repair. With preliminary proof of concept, it is now our goal to fine-tune this procedure to determine the various factors that will lead to the highest quality tissue from a biomechanical standpoint and the fastest cell proliferation rates in culture. The basis for this step assumes that natural in-vivo conditions are optimal for in-vitro culture and that if we can simulate in-vivo forces or strains for a variety of activities we can precondition the implant and cells to the signals they will receive after surgery. However, these in-vivo force patterns are generally not known for a tissue for different activities and likely vary from tendon to tendon. Knowing tendon and ligament forces during normal activities is important in order to understand the levels of in-vivo forces the constructs will be expected to bear once implanted. While researchers have to date failed to develop tissue-engineered replacements that match the ultimate mechanical properties of normal tissues, it is conceivable that less stringent design requirements based on normal activity forces (rather than ultimate or failure properties) may be sufficient for functional efficacy. The purpose of this research study was to determine the in-vivo force-time patterns acting on the rabbit patellar tendon and Achilles tendon models for two speeds of activity and for two inclinations of activity. In addition, we sought to determine the failure properties of these tissues so as to compute safety factors (i.e. ratios of failure tissue force to in-vivo operating force). This data will provide design parameters for preparing tissue engineered implants containing mesenchymal stem cells (MSCs) that will more effectively repair surgical defects in (open full item for complete abstract)

Committee: Dr. David L. Butler (Advisor) Subjects:

Master of Science in Biological Sciences, Youngstown State University, 2021, Department of Biological Sciences and Chemistry

The calcaneal (Achilles) tendon is capable of handling tremendous tensile loads during locomotion. However, cases of Achilles tendon ruptures have increased in recent years, requiring long healing times. Repaired tendons are more prone to re-rupture after healing, which may negatively impact patient quality of life. Thus, there exists a need for new methods of treatment aimed to improve and accelerate tendon healing. We studied the effect a combination of collagen, platelet-rich plasma (PRP), and mesenchymal stromal cells (MSC) on healing a complete Achilles tendon rupture in a Lewis rat model. The PRP was produced from rat blood collected during exsanguination procedures. MSCs from rat bone marrow met the criteria to be considered stem cells in a rat model, as they were seen to be plastic adherent and capable of tri-lineage differentiation. Rupture was surgically simulated by a full-thickness transection of the tendon, followed by surgical repair. All treatments included a strip of CollaTapeTM wrapped around the repair, acting as a vehicle for the biologics prior to closure of the wound. A single, 100µL subcutaneous injection of MSCs, PRP, or both were administered adjacent to the incision and assigned 1- or 2-week recovery periods before harvesting the operated and unoperated tendons. We observed promising trends which show an increase in gene expression activity in the treated tendons and differences in the expression of Col1a1 and Col3a1 which align with our predicted response to the treatments. However, due to contamination of the GAPDH RT-PCR results, the collagen analysis results remain inconclusive. The biomechanical properties of the tendons were determined using force-extension analysis. When normalized as a percent of the unoperated tendon, a significant improvement was seen in the strain at failure and in ultimate tensile strength after only one week of recovery in the rats who received any biological treatments used in this study, when compared to a sur (open full item for complete abstract)

Committee: Diana Fagan PhD (Advisor); Gary Walker PhD (Committee Member); Carmen Panaitof PhD (Committee Member) Subjects: Biology; Biomechanics; Biomedical Research; Physiology; Surgery

Master of Science in Biological Sciences, Youngstown State University, 2019, Department of Biological Sciences and Chemistry

The goal of this study was to improve the healing rate and strength of the Achilles tendon injury (rupture) following treatment with collagen, platelet-rich plasma (PRP) and bone-marrow derived mesenchymal stem cells (MSC). Achilles tendon rupture is the most frequent tendon injury in the body and it takes longer to heal due to the poor blood supply to it. This research investigated the effort on healing rate and strength of the tendon, following the addition of collagen, platelet rich plasma and bone marrow derived mesenchymal stem cells to a repaired Achilles tendon in a rat model. Platelet rich plasma was prepared from blood obtained from the rats and Bone marrow mesenchymal stem cells were also obtained from the femur and tibia of the same rats. A differentiation assay was performed to determine, if the cells used for this study were indeed stem cells. The cells differentiated into osteocytes, chondrocytes and adipocytes when given growth factors needed for these cell lineages. Rat surgeries were performed on the right legs of rats to cut the Achilles tendon 3mm above the calcaneal bone, which was then repaired. Treatments were given based on the groups the rats belong to; collagen only group, collagen and platelet rich plasma group, collagen and MSC or the three biologics group. Rats were euthanized at week 1 and 2 and their Achilles were harvested for biomechanical testing. Rats that received the three biological materials recorded the highest stress (tensile strength) and strain (elasticity) after a week of recovered however, strains and stress of the collagen only group was almost as high as that of the three biologics group. The MSC+ collagen group recorded the same strain as the three biologics group. There was no significant difference between the stress and strain among the groups at week two. The results indicated that all the treatment groups healed at the same rate at week two. However, MSC and PRP may play a significant role in increasing the tensile (open full item for complete abstract)

Committee: Diana Fagan PhD (Advisor); Gary Walker PhD (Committee Member); Carl Johnston PhD (Committee Member) Subjects: Biology; Biomedical Research; Immunology; Surgery

Master of Science in Engineering, Youngstown State University, 2019, Department of Mechanical, Industrial and Manufacturing Engineering

It is estimated that about 18 out of 100,000 people rupture their Achilles tendon every year. A review of 4000 Achilles tendon ruptures found that 75% were related to sports activities. Currently, the methods for fixing Achilles tendon ruptures are in need of improvement. Due to the prevalence of Achilles tendon injuries in sports and the fact that tendons have poor wound healing, there has been an abundance of studies on treatments for Achilles tendon injuries. Many different techniques and therapies using biologics have been researched. One area, however, that has not been well researched is the addition of a combination of mesenchymal stromal cells and platelet-rich plasma as a treatment method for wound healing enhancement. There is also a lack of studies comparing different treatment methods as they progress through time. This study chose the following treatment methods: collagen (CoTa); collagen and platelet-rich plasma (PRP); collagen and mesenchymal stromal cells (MSC); and collagen, platelet-rich plasma, and mesenchymal stromal cells (CPM) to follow through two recovery times: 1 week and 2 weeks. Lewis rats were chosen and a full transection of the right Achilles tendon was performed 6 mm proximal to the calcaneal bone. At 1 or 2 weeks both Achilles tendons of the rats were extracted and tensile tests were performed. Maximum force, engineering stress, strain, modulus of elasticity, total strain energy, and elastic strain energy were determined. Differences in the treatment groups at 1 week recovery were notable, no differences were found between the treatment groups at 2 week recovery, however differences could be seen when compared to the left virgin tissue controls. Computational modeling led to preliminary finite element models for each treatment group. Validation for each model was achieved by comparison with experimental data. Further development of the finite element analysis would allow for a more accurate model and allow for better comparisons betwe (open full item for complete abstract)

Committee: Hazel Marie PhD (Advisor); Diana Fagan PhD (Committee Member); Virgil Solomon PhD (Committee Member); Jason Walker PhD (Committee Member) Subjects: Biomechanics; Biomedical Engineering; Biomedical Research