Browsing by Author "Kretlow, James D."
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Item Autologously Generated Tissue-Engineered Bone Flaps for Reconstruction of Large Mandibular Defects in an Ovine Model(Mary Ann Liebert, Inc., 2015) Tatara, Alexander M.; Kretlow, James D.; Spicer, Patrick P.; Lu, Steven; Lam, Johnny; Liu, Wei; Cao, Yilin; Liu, Guangpeng; Jackson, John D.; Yoo, James J.; Atala, Anthony; van den Beucken, Jeroen J.J.P.; Jansen, John A.; Kasper, F. Kurtis; Ho, Tang; Demian, Nagi; Miller, Michael John; Wong, Mark E.; Mikos, Antonios G.The reconstruction of large craniofacial defects remains a significant clinical challenge. The complex geometry of facial bone and the lack of suitable donor tissue often hinders successful repair. One strategy to address both of these difficulties is the development of an in vivo bioreactor, where a tissue flap of suitable geometry can be orthotopically grown within the same patient requiring reconstruction. Our group has previously designed such an approach using tissue chambers filled with morcellized bone autograft as a scaffold to autologously generate tissue with a predefined geometry. However, this approach still required donor tissue for filling the tissue chamber. With the recent advances in biodegradable synthetic bone graft materials, it may be possible to minimize this donor tissue by replacing it with synthetic ceramic particles. In addition, these flaps have not previously been transferred to a mandibular defect. In this study, we demonstrate the feasibility of transferring an autologously generated tissue-engineered vascularized bone flap to a mandibular defect in an ovine model, using either morcellized autograft or synthetic bone graft as scaffold material.Item Biomaterial-based strategies for craniofacial tissue engineering(2010) Kretlow, James D.; Mikos, Antonios G.Damage to or loss of craniofacial tissues, often resulting from neoplasm, trauma, or congenital defects, can have devastating physical and psychosocial effects. The presence of many specialized tissue types integrated within a relatively small volume leads to difficulty in achieving complete functional and aesthetic repair. Tissue engineering offers a promising alternative to conventional therapies by potentially enabling the regeneration of normal native tissues. Initially, a stimulus responsive biomaterial designed for injectable cell delivery applications was investigated with the goal of providing a substrate for osteogenic differentiation of delivered cells. In order to enable faster clinical translation, later efforts focused on novel combinations of regulated materials. Most common approaches using cell delivery for bone tissue engineering involve the harvest and ex vivo expansion of progenitor cell populations over multiple weeks and cell passages. The effect of aging and passage on proliferation and differentiation were analyzed using murine mesenchymal stem cells as a model. These cells lose their ability to proliferate and differentiate with increases in donor age and passages during cell culture. Delivery of uncultured bone marrow mononuclear cells was then investigated, and it was determined that when delivered to porous scaffolds these cells, which can be harvested, isolated, and returned to the body within the setting of a single operation, significantly increased bone regeneration in vivo. Finally, because these techniques of scaffold implantation and cell delivery would likely fail if delivered to an exposed or infected wound, a method of space maintenance was investigated. Space maintainers made of poly(methyl methacrylate) and having tunable porosity and pore interconnectivity were evaluated within a clean/contaminated mandibular defect. Low porosity space maintainers were found to prevent soft tissue collapse or contracture into the bony defect and allowed surrounding soft tissues to penetrate the pores of the implant, enabling healing over 12 weeks. The tissue response and wound healing characteristics of these implant was favorable when compared to solid or high porosity implants. Although optimization and further investigation of these techniques is necessary, in combination these approaches demonstrate one possible and translatable approach towards craniofacial tissue regeneration.Item Combined space maintenance and bone regeneration system for the reconstruction of large osseous defects(2017-01-03) Mikos, Antonios G.; Wong, Mark E.; Young, Simon W.; Kretlow, James D.; Shi, Meng; Kasper, Kurtis F.; Spicer, Patrick; Rice University; United States Patent and Trademark OfficeSystems, methods and compositions useful for treatment of traumatic bone injuries are provided. In one embodiment, a bone reconstruction system comprising a space maintaining composition comprising porous polymethylmethacrylate; and an osseous generating construct comprising a polymethylmethacrylate chamber that comprises one or more osseous generating materials is provided. Associated compositions and methods are also provided.Item Evaluation of antibiotic releasing porous polymethylmethacrylate space maintainers in an infected composite tissue defect model(Elsevier, 2013-11) Spicer, Patrick P.; Shah, Sarita R.; Henslee, Allan M.; Watson, Brendan M.; Kinard, Lucas A.; Kretlow, James D.; Bevil, Kristin; Kattchee, Lauren; Bennett, George N.; Demian, Nagi M.; Mende, Katrin; Murray, Clinton K.; Jansen, John A.; Wong, Mark E.; Mikos, Antonios G.; Kasper, F.KurtisThis study evaluated the in vitro and in vivo performance of antibiotic-releasing porous polymethylmethacrylate (PMMA)-based space maintainers comprising a gelatin hydrogel porogen and a poly(DL-lactic-co-glycolic acid) (PLGA) particulate carrier for antibiotic delivery. Colistin was released in vitro from either gelatin or PLGA microparticle loaded PMMA constructs, with gelatin-loaded constructs releasing colistin over approximately 7 days and PLGA microparticle-loaded constructs releasing colistin up to 8 weeks. Three formulations with either a burst release or extended release in different doses were tested in a rabbit mandibular defect inoculated with Acinetobacter baumannii (2 × 107 colony forming units/mL). In addition, one material control that released antibiotic but was not inoculated with A. baumannii was tested. A. baumannii was not detectable in any animal after 12 weeks by culture of the defect, saliva, or blood. Defects with high-dose, extended-release implants had greater soft tissue healing compared to defects with burst release implants, with 8 out of 10 animals showing healed mucosae compared to 2 out of 10 with healed mucosae, respectively. Extended release of locally delivered colistin via a PLGA microparticle carrier improved soft tissue healing over the implants compared to burst release of colistin from a gelatin carrier.Item Evaluation of Bone Regeneration Using the Rat Critical Size Calvarial Defect(Nature Publishing Group, 2012-10) Spicer, Patrick P.; Kretlow, James D.; Young, Simon; Jansen, John A.; Kasper, F. Kurtis; Mikos, Antonios G.Animal models that are reliably reproducible, appropriate analogues to the clinical condition they are used to investigate, and that offer minimal morbidity and periprocedural mortality to the subject are the keystone to the preclinical development of translational technologies. For bone tissue engineering, a number of small animal models exist. Here we describe the protocol for one such model, the rat calvarial defect. This versatile model allows for evaluation of biomaterials and bone tissue engineering approaches within a reproducible, nonload-bearing orthotopic site. Critical steps to ensure appropriate experimental control and troubleshooting tips learned through extensive experience with this model are provided. The surgical procedure itself takes approximately 30 minutes to complete with approximately 2 hours of perioperative care, and tissue harvest is generally performed 4 to 12 weeks postoperatively. Several analytical techniques are presented, which evaluate the cellular and extracellular matrix components, functionality and mineralization, including histological, mechanical and radiographic methods.