Browsing by Author "Park, Kinam"
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Item Baseline Biomechanical Properties of Epithelia prior to Tissue Expansion in Dogs(Lippincott, Williams & Wilkins, 2018-05-14) Bowling, Jay; Davidson, Darrell D.; Tholpady, Sunil S.; Park, Kinam; Eckert, George J.; Katona, Terrence; Chu, Tien-Min G.; Barco, Clark T.; Periodontology, School of DentistryBackground: Soft-tissue deficiencies pose a challenge in a variety of disease processes when the end result is exposure of underlying tissue. Although multiple surgical techniques exist, the transposition of tissue from one location to another can cause donor-site morbidity, long incisions prone to dehiscence, and poor patient outcomes as a result. Use of tissue expansion prior to grafting procedures has been shown to have success in increasing available soft tissue to aid in repairing wounds. However, the current tissue expanders have biomechanical limits to the extent and rate of expansion that usually exceeds the tissue capacity, leading to incisional dehiscence or expander extrusion. Understanding the baseline biomechanical properties of the tissue to be expanded would provide useful information regarding surgical protocol employed for a given anatomical location. Therefore, the aim of this study was to test and compare the baseline (preexpansion) biomechanical properties of different common expansion sites in dogs. Methods: Four samples measuring approximately 20 × 15 × 1 mm were harvested from 8 dogs. The samples were collected from the hard palate, alveolar mucosa, scalp, and chest of the animal and analyzed for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength using a Texture Technologies TA.XT texture analyzer with corresponding biomechanical measurement software. Samples were compared as to their baseline biomechanical properties prior to any soft-tissue expansion. Histological sections of the samples were analyzed using hematoxylin eosin in an attempt to correlate the histological description to the biomechanical properties seen during testing. Summary statistics (mean, standard deviation, standard error, range) are reported for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength and for the histological parameters by intraoral site. Analysis of variance was used to compare the biomechanical and histological parameters among the 4 locations while accounting for multiple measurements from each dog. Results: The scalp had significantly higher maximum stress (σmax) than chest, mucosa, and palate (P < 0.0001), with no differences among the other 3 locations (P > 0.63). Scalp site also had significantly higher maximum tangential modulus (ε) than chest, mucosa, and palate (P < 0.006), with no differences among the other 3 locations (P > 0.17). The locations did not have significantly different maximum tangential stiffness (k; P = 0.72). Histologically, 2 separate patterns of collagen disruption were evident. Conclusion: Although different results were obtained than theorized, this study showed that the scalp had the greatest resiliency to expand prior to tearing, and the highest tangential modulus, with all sites having statistically similar modulus of elasticity. Based on this study, the scalp could be expanded more aggressively compared with the other sites.Item Development and Evaluation of Transferrin-Stabilized Paclitaxel Nanocrystal Formulation(Elsevier, 2014-02-28) Lu, Ying; Wang, Zhao-hui; Li, Tonglei; McNally, Helen; Park, Kinam; Sturek, Michael; Department of Cellular & Integrative Physiology, IU School of MedicineThe aim of the present study was to prepare and evaluate a paclitaxel nanocrystal-based formulation stabilized by serum protein transferrin in a non-covalent manner. The pure paclitaxel nanocrystals were first prepared using an antisolvent precipitation method augmented by sonication. The serum protein transferrin was selected for use after evaluating the stabilizing effect of several serum proteins including albumin and immunoglobulin G. The formulation contained approximately 55~60% drug and was stable for at least 3 months at 4 °C. In vivo antitumor efficacy studies using mice inoculated with KB cells demonstrate significantly higher tumor inhibition rate of 45.1% for paclitaxel-transferrin formulation compared to 28.8% for paclitaxel nanosuspension treatment alone. Interestingly, the Taxol® formulation showed higher antitumor activity than the paclitaxel-transferrin formulation, achieving a 93.3% tumor inhibition rate 12 days post initial dosing. However, the paclitaxel-transferrin formulation showed a lower level of toxicity, which is indicated by steady increase in body weight of mice over the treatment period. In comparison, treatment with Taxol® resulted in toxicity issues as body weight decreased. These results suggest the potential benefit of using a serum protein in a non-covalent manner in conjunction with paclitaxel nanocrystals as a promising drug delivery model for anticancer therapy.Item Microparticles Produced by the Hydrogel Template Method for Sustained Drug Delivery(Elsevier, 2014-01-30) Lu, Ying; Sturek, Michael; Park, Kinam; Department of Cellular & Integrative Physiology, IU School of MedicinePolymeric microparticles have been used widely for sustained drug delivery. Current methods of microparticle production can be improved by making homogeneous particles in size and shape, increasing the drug loading, and controlling the initial burst release. In the current study, the hydrogel template method was used to produce homogeneous poly(lactide-co-glycolide) (PLGA) microparticles and to examine formulation and process-related parameters. Poly(vinyl alcohol) (PVA) was used to make hydrogel templates. The parameters examined include PVA molecular weight, type of PLGA (as characterized by lactide content, inherent viscosity), polymer concentration, drug concentration and composition of solvent system. Three model compounds studied were risperidone, methylprednisolone acetate and paclitaxel. The ability of the hydrogel template method to produce microparticles with good conformity to template was dependent on molecular weight of PVA and viscosity of the PLGA solution. Drug loading and encapsulation efficiency were found to be influenced by PLGA lactide content, polymer concentration and composition of the solvent system. The drug loading and encapsulation efficiency were 28.7% and 82% for risperidone, 31.5% and 90% for methylprednisolone acetate, and 32.2 % and 92 % for paclitaxel, respectively. For all three drugs, release was sustained for weeks, and the in vitro release profile of risperidone was comparable to that of microparticles prepared using the conventional emulsion method. The hydrogel template method provides a new approach of manipulating microparticles.Item Mucosal Perfusion Preservation by a Novel Shapeable Tissue Expander for Oral Reconstruction(Wolters Kluwer, 2017-08-28) Barwinska, Daria; Garner, John; Davidson, Darrell D.; Cook, Todd G.; Eckert, George J.; Tholpady, Sunil S.; March, Keith L.; Park, Kinam; Barco, Clark T.; Cellular and Integrative Physiology, School of MedicineBackground: There are few methods for expanding oral mucosa, and these often cause complications such as tissue necrosis and expander eruption. This study examines mucosal blood perfusion following insertion of a novel shapeable hydrogel tissue expander (HTE). The canine model used subgingival insertion of HTE following tooth extraction and alveolar bone reduction. The primary goal of this study was to gain understanding of epithelial perfusion and reparative responses of gingival mucosa during HTE expansion. Methods: Nine Beagle dogs underwent bilateral premolar maxillary and mandibular tooth extraction. Three to four months later, HTE-contoured inserts were implanted submucosally under the buccal surface of the alveolar ridge. After removal and following a 6- to 7-month period of healing, new HTE implants were inserted at the same sites. The area was assessed weekly for tissue perfusion and volume of expansion. Biopsies for histological analysis were performed at the time of expander removal. Results: Within 2 weeks following the second insertion, blood flow returned to baseline (defined as the values of perfusion measurements at the presurgery assessment) and remained normal until hydrogel full expansion and removal. Volume expansion analysis revealed that the hydrogel doubled in volume. Histological assessment showed no macrophage or inflammatory infiltration of the mucosa. No superficial fibrosis, decreased vascularity, or mucosal change was seen. Conclusion: Maintenance of adequate tissue perfusion is a clinically important aspect of tissue expander performance to reduce risk of device loss or injury to the patient, particularly for areas with a history of previous surgeries.Item Neuroprotective Ferulic Acid (FA)-Glycol Chitosan (GC) Nanoparticles for Functional Restoration of Traumatically Injured Spinal Cord(Elsevier B.V., 2014-02) Wu, Wei; Lee, Seung-Young; Wu, Xiangbing; Tyler, Jacqueline Y.; Wang, He; Ouyang, Zheng; Park, Kinam; Xu, Xiao-Ming; Cheng, Ji-Xin; Department of Neurological Surgery, IU School of MedicineAn urgent unmet need exists for early-stage treatment of spinal cord injury (SCI). Currently methylprednisolone is the only therapeutic agent used in clinics, for which the efficacy is controversial and the side effect is well-known. We demonstrated functional restoration of injured spinal cord by self-assembled nanoparticles composed of ferulic acid modified glycol chitosan (FA-GC). Chitosan and ferulic acid are strong neuroprotective agents but their systemic delivery is difficult. Our data has shown a prolonged circulation time of the FA-GC nanoparticles allowing for effective delivery of both chitosan and ferulic acid to the injured site. Furthermore, the nanoparticles were found both in the gray matter and white matter. The in vitro tests demonstrated that nanoparticles protected primary neurons from glutamate-induced excitotoxicity. Using a spinal cord contusion injury model, significant recovery in locomotor function was observed in rats that were intravenously administered nanoparticles at 2 h post injury, as compared to non-improvement by methylprednisolone administration. Histological analysis revealed that FA-GC treatment significantly preserved axons and myelin and also reduced cavity volume, astrogliosis, and inflammatory response at the lesion site. No obvious adverse effects of nanoparticles to other organs were found. The restorative effect of FA-GC presents a promising potential for treating human SCIs.Item Recapitulation of complex transport and action of drugs at tumor microenvironment using tumor-microenvironment-on-chip(Elsevier, 2016-09-28) Han, Bumsoo; Qu, Chunjing; Park, Kinam; Konieczny, Stephen F.; Korc, Murray; Medicine, School of MedicineTargeted delivery aims to selectively distribute drugs to targeted tumor tissue but not to healthy tissue. This can address many of clinical challenges by maximizing the efficacy but minimizing the toxicity of anti-cancer drugs. However, complex tumor microenvironment poses various barriers hindering the transport of drugs and drug delivery systems. New tumor models that allow for the systematic study of these complex environments are highly desired to provide reliable test beds to develop drug delivery systems for targeted delivery. Recently, research efforts have yielded new in vitro tumor models, the so called tumor-microenvironment-on-chip, that recapitulate certain characteristics of the tumor microenvironment. These new models show benefits over other conventional tumor models, and have the potential to accelerate drug discovery and enable precision medicines. However, further research is warranted to overcome their limitations and to properly interpret the data obtained from these models. In this article, key features of the in vivo tumor microenvironment that are relevant to drug transport processes for targeted delivery was discussed, and the current status and challenges for developing in vitro transport model systems was reviewed.Item Reshapeable hydrogel tissue expander for ridge augmentation: Results of a series of successive insertions at the same intraoral site(Wiley, 2019) Garner, John; Davidson, Darrell D.; Barwinska, Daria; Eckert, George J.; Tholpady, Sunil S.; Park, Kinam; Barco, Clark T.; Pathology and Laboratory Medicine, School of MedicineBackground Tissue expansion of oral mucosa prior to ridge augmentation promises to reduce the soft tissue exposure and improve the final intraoral bone graft density and volume. This study explored a novel, shapeable hydrogel tissue expander (HTE) in intraoral sites that had undergone previous expansion and surgery. Methods Nine beagle dogs had all premolar teeth extracted with alveolar bone reduction. At least 3 months healing followed before placing the hydrogels at 4 sites for each dog: maxilla and mandible, right and left. After 6 weeks of expansion, the expanded hydrogels were removed and measured for volume expansion and hydrogel condition. Punch biopsies were taken of the expanded oral mucosa. After healing of 3 months a second insertion of hydrogels was done at the same sites. Again, volume and hydrogel condition were recorded. Three dogs received ultrasound imaging of the expanding hydrogels upon the second insertion. Necropsy specimens were taken of both expanded and non‐expanded oral mucosa. Results Blood flow returned to that observed before insertion within two weeks after HTE insertion in both first and second insertions. First insertion resulted in linear gain of 8.13 mm, and second insertion showed a linear gain of 6.44 mm of oral mucosa. First and second insertion erupted at approximately 3% and 4% of the sites, respectively. There was no directional migration of the expanding hydrogels. Histology indicated little inflammatory reaction to any hydrogel implant. Conclusion Oral mucosa can be consistently and successfully expanded prior to bone graft for ridge augmentation even at sites with a history of prior surgeries.