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Falls among the elderly are a major source of injury, often leading to serious fractures, hospitalization, and death. Osteoporosis (OP) is a global problem intimately related with these fractures, characterized by reduced bone mass, increased bone fragility. There exists a high failure rate in the translation of treatments to osteoporotic populations. Mesenchymal stromal cell (MSC) transplantation as a therapeutic strategy for OP has not yet been examined in clinical trials. This may be attributed to the mixed findings of pre-clinical studies aimed at determining the efficacy of MSC therapy towards bone regeneration in OP. The most common animal model of OP is ovariectomy (OVX) that simulates post-menopausal estrogen loss. A plethora of bone regeneration studies have used OVX models with 12-16 weeks post-OVX periods and have generally reported positive results from a variety of treatment modalities, including MSC therapy. However, the use of the minimum post-OVX period may not be appropriate to reflect the global changes in regenerative potential of OP patients. In our research group's previous study, MSC were isolated from a minimum 60 week post-OVX rat model, representing a severe case of OP. The MSC isolated from these animals are a unique cell population that we expect may better represent the outcomes of autologous cell therapies for the older patient population in the clinic. In the present study, adipose and bone marrow derived MSC from OVX and age-matched animals were evaluated for their osteogenic and adipogenic differentiation potentials in culture through passage 10. Results from this study suggest that bone marrow derived-MSC maintain their phenotype and functionality more effectively than adipose derived-MSC in OP. Further investigations used regenerative medicine approaches for cell expansion on keratin protein coated microcarriers in static culture. Hair-derived keratin biomaterials have demonstrated their utility as carriers of biologics and drugs for tissue engineering. An optimal microcarrier was selected that demonstrated superior retention of the protein coating through electrostatic interactions and high cell viability. Finally, the integration of cell-microcarriers into a perfusion bioreactor system was explored. Preliminary results demonstrated the feasibility of MSC growth and differentiation on microcarrier based packed beds. Moreover, AD-MSC from OP rats were unresponsive to both inductive media and shear stress related osteogenic cues. These results highlight the complexity and challenges associated with the MSC regenerative strategy. / Doctor of Philosophy / Osteoporosis is a skeletal disease that results in reduced bone mass, increased bone fragility and fracture risk. Osteoporotic patients who experience falls suffer serious fractures, hospitalization, and poor bone healing. Several different therapies have been developed for the treatment of osteoporosis, though many are unable to translate from the bench to the clinical population. A popular treatment being investigated is the application of mesenchymal stromal cells (MSC) for fracture repair and the reversal of osteoporotic bone losses. However, cells isolated from aged and osteoporotic patients have been shown to have deficient bone forming properties. Nevertheless, animal models of osteoporosis applying this treatment report amelioration of bone loss. This work seeks to examine a more clinically relevant rat model of osteoporosis. Typical osteoporosis models use an ovariectomy procedure to simulate post-menopausal bone loss on relatively young animals and conduct short-term studies. These studies may not accurately reflect the global regenerative changes in osteoporosis patients or the impaired MSC properties. Adipose and bone marrow derived MSC from a long term ovariectomy model were investigated for their regenerative potentials. MSC growth and bone forming potential was evaluated on keratin protein coated microcarriers in both static and perfusion cultures. Results from this study suggest that bone marrow derived MSC maintain their phenotype and functionality more effectively than adipose derived MSC in osteoporosis. Further preliminary results demonstrated the feasibility of MSC growth and differentiation on microcarrier based packed beds. These results highlight the complexity and challenges associated with the MSC regenerative strategy.

Yes / Healthcare applications are known to have a considerable environmental impact and the use of bio-based polymers has emerged as a powerful approach to reduce the carbon footprint in the sector. This research aims to explore the suitability of using a new sustainable polyester blend (Floreon™) as a scaffold directed to aid in musculoskeletal applications. Musculoskeletal problems arise from a wide range of diseases and injuries related to bones and joints. Specifically, bone injuries may result from trauma, cancer, or long-term infections and they are currently considered a major global problem in both developed and developing countries. In this work we have manufactured a series of 3D-printed constructs from a novel biopolymer blend using fused deposition modelling (FDM), and we have modified these materials using a bioceramic (wollastonite, 15% w/w). We have evaluated their performance in vitro using human dermal fibroblasts and rat mesenchymal stromal cells. The new sustainable blend is biocompatible, showing no differences in cell metabolic activity when compared to PLA controls for periods 1-18 days. FloreonTM blend has proven to be a promising material to be used in bone tissue regeneration as it shows an impact strength in the same range of that shown by native bone (just under 10 kJ/m2) and supports an improvement in osteogenic activity when modified with wollastonite. / We would like to acknowledge the Medical Research Council in the UK (MRC) for funding this research throughout a MRC Proximity to Discovery award (P2D) with grant number MC_PC_16084. We would also like to acknowledge CONACYT for funding DH RamosRodriguez’s work.

Yes / Brushite, or Dicalcium phosphate dihydrate (CaHPO4⋅2H2O), is a well-known calcium phosphate (CaP) found in mineralized tissues and is utilized in medical treatment, particularly in bone powder for bone repair. Brushites with Zn2+ and Ag + ions concentration were synthesized in an aqueous solution using the conventional precipitation procedure. The synthesized brushites were characterized using techniques such as Fourier Transform Infrared Spectroscopy (FTIR), Powder X-ray diffraction (PXRD), Scanning Electron Microscopy (SEM), and bioassays were carried out to evaluate their antibacterial and antifungal activities. The alterations in PXRD and FTIR peak locations demonstrated that zinc and silver ions were effectively inserted into the brushite crystals. Initial tests revealed that the powders were innocuous, which make them potentially beneficial for mineralized tissue engineering. These brushites exhibited remarkable antimicrobial activities. Zn-doped brushite completely controlled the growth of fungi namely Macrophomina phaseolina and Sclerotium rolfsii at a concentration of 0.0039 mg mL-1 while Ag-doped brushite completely arrested the growth of these fungi at 0.0312 and 0.0039 mg mL-1, respectively. Likewise, both the brushite exhibited remarkable antibacterial activity against Bacillus thuringiensis and moderate activity against Escherichia coli. Brushite compounds coupled with active metal ions, notably Ag+ and Zn2+, demonstrated promise as a distinct class of reactive materials for bone-related applications.

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A presença da hipertensão arterial pode comprometer a qualidade da reparação óssea, pois a doença é caracterizada por alterações fisiopatológicas vasculares e do metabolismo mineral. Com o objetivo de avaliar a neoformação e o remodelamento ósseo, este trabalho investigou o processo da reparação óssea em ratos geneticamente hipertensos (SHR) e de seus controles Wistar-Kyoto (WKY). Defeitos bicorticais de 2mm de diâmetro no lado direito e de 5mm no lado esquerdo, foram realizados com trefinas na região do ângulo de mandíbula. Os animais, divididos em grupos de cinco indivíduos cada, foram sacrificados após 2, 3, 5, 10, 15, 30, 60 e 90 dias pós-operatórios; as mandíbulas foram removidas, fixadas em formol a 10%, descalcificadas em ácido fórmico a 20%, incluídas em parafina e as secções histológicas, de 7m de espessura, coradas com hematoxilina e eosina. As imagens foram capturadas com aumento de 40x e a área do defeito mensurada pelo programa de histometria digital Image J versão 1.4. A análise estatística revelou que não houve diferença significante na comparação entre as linhagens WKY e SHR (p = 0,884), independente dos períodos ou lados avaliados; entre períodos, nas linhagens WKY (p = 0,101) e SHR (p = 0,479), independente dos lados avaliados; entre períodos por linhagens no lado direito; e entre linhagens por lados, esquerdo com p = 0,466 e direito com p = 0,689, independente do fator período. Houve diferença estatisticamente significante entre o lado esquerdo e o direito (p < 0,001), independente das linhagens e períodos avaliados; entre os lados por linhagens, WKY e SHR, ambas com p < 0,001; entre períodos por linhagens no lado esquerdo, no qual o grupo WKY de 15 dias apresentou área menor que o grupo WKY de 60 dias e o grupo SHR de 10 dias, e o grupo WKY de 60 dias apresentou área maior que o grupo SHR de 30 dias e SHR de 60 dias. Apesar das alterações encontradas no lado esquerdo, que podem ser atribuídas à remodelação funcional do osso da mandíbula, não houve diferenças significantes na reparação do defeito de 5mm e de 2mm entre ratos espontaneamente hipertensos e de seus controles Wistar-Kyoto. / Arterial hypertension may affect the quality of bone repair because this disease is characterized by physiopathological vascular and bone metabolism changes. With the objective of evaluating the bone neoformation and remodeling, this study investigated the process of bone repair in spontaneously hypertensive rats (SHR) and their match controls Wistar-Kyoto (WKY). Through-in-through defects were done with trephine burs in the mandibular angle area, of 2mm diameter on the right side and 5mm diameter on the left side. The animals were divided into groups of five individuals each one and killed after 2, 3, 5, 10, 15, 30, 60 and 90 postoperative days; the mandibles were removed, fixed in 10% formalin solution, decalcified with 20% formic acid, and embedded in paraffin; the histological sections of 7m thickness were stained with hematoxylin and eosin. The images were captured with 40x magnification and the defect area was measured by the image processing program Image J version 1.4. The statistical analysis showed that there is no significant difference in the comparison of WKY and SHR strains (p = 0,884), independent of periods or sides; among periods, in the WKY strain (p = 0,101) and SHR one (p = 0,479), independent of sides; among periods by strains on the right side; and among strains by sides, left side with p = 0,466 and right side with p = 0,689, independent of periods. There is a significant difference between left and right side (p < 0,001), independent of strains and periods; between sides by strains, WKY and SHR, both with p < 0,001; among periods by strains on the left side, which WKY 15 days group showed an area smaller than WKY 60 days and SHR 10 days groups, and WKY 60 days group showed an area bigger than SHR 30 days and SHR 60 days groups. Despite the changes founded on the left side that could be attributed to the functional remodeling of the mandibular bone, there were no differences in the bone repair of 5mm and 2mm diameter defects between spontaneously hypertensive rats and their match controls Wistar-Kyoto.

A presença da hipertensão arterial pode comprometer a qualidade da reparação óssea, pois a doença é caracterizada por alterações fisiopatológicas vasculares e do metabolismo mineral. Com o objetivo de avaliar a neoformação e o remodelamento ósseo, este trabalho investigou o processo da reparação óssea em ratos geneticamente hipertensos (SHR) e de seus controles Wistar-Kyoto (WKY). Defeitos bicorticais de 2mm de diâmetro no lado direito e de 5mm no lado esquerdo, foram realizados com trefinas na região do ângulo de mandíbula. Os animais, divididos em grupos de cinco indivíduos cada, foram sacrificados após 2, 3, 5, 10, 15, 30, 60 e 90 dias pós-operatórios; as mandíbulas foram removidas, fixadas em formol a 10%, descalcificadas em ácido fórmico a 20%, incluídas em parafina e as secções histológicas, de 7m de espessura, coradas com hematoxilina e eosina. As imagens foram capturadas com aumento de 40x e a área do defeito mensurada pelo programa de histometria digital Image J versão 1.4. A análise estatística revelou que não houve diferença significante na comparação entre as linhagens WKY e SHR (p = 0,884), independente dos períodos ou lados avaliados; entre períodos, nas linhagens WKY (p = 0,101) e SHR (p = 0,479), independente dos lados avaliados; entre períodos por linhagens no lado direito; e entre linhagens por lados, esquerdo com p = 0,466 e direito com p = 0,689, independente do fator período. Houve diferença estatisticamente significante entre o lado esquerdo e o direito (p < 0,001), independente das linhagens e períodos avaliados; entre os lados por linhagens, WKY e SHR, ambas com p < 0,001; entre períodos por linhagens no lado esquerdo, no qual o grupo WKY de 15 dias apresentou área menor que o grupo WKY de 60 dias e o grupo SHR de 10 dias, e o grupo WKY de 60 dias apresentou área maior que o grupo SHR de 30 dias e SHR de 60 dias. Apesar das alterações encontradas no lado esquerdo, que podem ser atribuídas à remodelação funcional do osso da mandíbula, não houve diferenças significantes na reparação do defeito de 5mm e de 2mm entre ratos espontaneamente hipertensos e de seus controles Wistar-Kyoto. / Arterial hypertension may affect the quality of bone repair because this disease is characterized by physiopathological vascular and bone metabolism changes. With the objective of evaluating the bone neoformation and remodeling, this study investigated the process of bone repair in spontaneously hypertensive rats (SHR) and their match controls Wistar-Kyoto (WKY). Through-in-through defects were done with trephine burs in the mandibular angle area, of 2mm diameter on the right side and 5mm diameter on the left side. The animals were divided into groups of five individuals each one and killed after 2, 3, 5, 10, 15, 30, 60 and 90 postoperative days; the mandibles were removed, fixed in 10% formalin solution, decalcified with 20% formic acid, and embedded in paraffin; the histological sections of 7m thickness were stained with hematoxylin and eosin. The images were captured with 40x magnification and the defect area was measured by the image processing program Image J version 1.4. The statistical analysis showed that there is no significant difference in the comparison of WKY and SHR strains (p = 0,884), independent of periods or sides; among periods, in the WKY strain (p = 0,101) and SHR one (p = 0,479), independent of sides; among periods by strains on the right side; and among strains by sides, left side with p = 0,466 and right side with p = 0,689, independent of periods. There is a significant difference between left and right side (p < 0,001), independent of strains and periods; between sides by strains, WKY and SHR, both with p < 0,001; among periods by strains on the left side, which WKY 15 days group showed an area smaller than WKY 60 days and SHR 10 days groups, and WKY 60 days group showed an area bigger than SHR 30 days and SHR 60 days groups. Despite the changes founded on the left side that could be attributed to the functional remodeling of the mandibular bone, there were no differences in the bone repair of 5mm and 2mm diameter defects between spontaneously hypertensive rats and their match controls Wistar-Kyoto.

Indiana University-Purdue University Indianapolis (IUPUI) / The objective of this study was to evaluate the in vivo performance of the novel press-fit dental implant fabricated via electron beam melting (EBM, Southern Methodist Univ.) and compare it to a commercially-available porous-coated press-fit dental implant (Endopore, Innova Corp.). Twelve cylindrical shaped implants 3 mm in diameter x 5 mm long were made by EBM (Southern Methodist Univ.) using Ti6Al4V ELI alloy. Twelve commercial implants (Endopore, Innova Corp.) of the same geometry were used as controls. Samples were implanted in rabbit tibia and retrieved six weeks postoperatively. Six specimens from each implant type were embedded undecalcified, sectioned, and stained with toluidine blue (Sigma) for histomorphometry analysis. Bone-to-implant contact (BIC) was measured. On the six remaining samples from each implant type, the mechanical properties were evaluated by pushout test on a material testing machine. The samples were loaded at a loading rate of 1 mm/min. The pushout strength was measured and the apparent shear stiffness was calculated. The results were analyzed with a paired-t test. The histology shows osteointegration of surrounding bone with both implant types. Bone was found to grow into the porous space between the beads. Both the Endopore (Innova Corp.) and the EBM (Southern Methodist Univ.) showed similar BIC. The mean BIC for the Endopore (Innova Corp.) and EBM (Southern Methodist Univ.) implant were 35 ± 6% and 32 ± 9%, respectively. It failed to reach statistical significance (p > 0.05). The peak pushout force for Endopore (Innova Corp.) and EBM (Southern Methodist Univ.) implants were 198.80 ± 61.29 N and 243.21 ± 69.75 N, respectively. The apparent shear stiffness between bone and implant for the Endopore (Innova Corp.) and EBM (Southern Methodist Univ.) implants were 577.36 ± 129.99 N/mm; and 584.48 ± 146.63 N/mm, respectively. Neither the peak pushout force nor the apparent shear stiffness of the implants was statistically different between the two groups (p > 0.05). The results suggest that the implants manufactured by EBM (Southern Methodist Univ.) perform equally well as the commercial implant Endopore (Innova Corp.) in this current animal model.

No description available.