Browsing by Author "Wong, Mark E."
Now showing 1 - 9 of 9
Results Per Page
Sort Options
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 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 Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair(Elsevier, 2014) Lu, Steven; Lam, Johnny; Trachtenberg, Jordan E.; Lee, Esther J.; Seyednejad, Hajar; van den Beucken, Jeroen J.J.P.; Tabata, Yasuhiko; Wong, Mark E.; Jansen, John A.; Mikos, Antonios G.; Kasper, F. KurtisThe present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formulations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair.Item Effects of Antibiotic Physicochemical Properties on Their Release Kinetics from Biodegradable Polymer Microparticles(Springer, 2014) Shah, Sarita R.; Henslee, Allan M.; Spicer, Patrick P.; Yokota, Shun; Petrichenko, Sophia; Allahabadi, Sachin; Bennett, George N.; Wong, Mark E.; Kasper, F. Kurtis; Mikos, Antonios G.Purpose: This study investigated the effects of the physicochemical properties of antibiotics on the morphology, loading efficiency, size, release kinetics, and antibiotic efficacy of loaded poly(DL-lactic-co-glycolic acid) (PLGA) microparticles (MPs) at different loading percentages. Methods: Cefazolin, ciprofloxacin, clindamycin, colistin, doxycycline, and vancomycin were loaded at 10 and 20 wt% into PLGA MPs using a water-in-oil-in water double emulsion fabrication protocol. Microparticle morphology, size, loading efficiency, release kinetics, and antibiotic efficacy were assessed. Results: The results from this study demonstrate that the chemical nature of loaded antibiotics, especially charge and molecular weight, influence the incorporation into and release of antibiotics from PLGA MPs. Drugs with molecular weights less than 600 Da displayed biphasic release while those with molecular weights greater than 1,000 Da displayed triphasic release kinetics. Large molecular weight drugs also had a longer delay before release than smaller molecular weight drugs. The negatively charged antibiotic cefazolin had lower loading efficiency than positively charged antibiotics. Microparticle size appeared to be mainly controlled by fabrication parameters, and partition and solubility coefficients did not appear to have an obvious effect on loading efficiency or release. Released antibiotics maintained their efficacy against susceptible strains over the duration of release. Duration of release varied between 17 and 49 days based on the type of antibiotic loaded. Conclusions: The data from this study indicate that the chemical nature of antibiotics affects properties of antibiotic-loaded PLGA MPs and allows for general prediction of loading and release kinetics.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 Osteochondral Tissue Regeneration using a Bilayered Composite Hydrogel with Modulating Dual Growth Factor Release Kinetics in a Rabbit Model(Elsevier, 2014) Kima, Kyobum; Lama, Johnny; Lua, Steven; Spicer, Patrick P.; Lueckgena, Aline; Yasuhiko, Tabata; Wong, Mark E.; Jansen, John A.; Mikos, Antonios G.; Kasper, F. KurtisBiodegradable oligo(poly(ethylene glycol) fumarate) (OPF) composite hydrogels have been investigated for the delivery of growth factors (GFs) with the aid of gelatin microparticles (GMPs) and stem cell populations for osteochondral tissue regeneration. In this study, a bilayered OPF composite hydrogel that mimics the distinctive hierarchical structure of native osteochondral tissue was utilized to investigate the effect of transforming growth factor-β3 (TGF-β3) with varying release kinetics and/or insulin-like growth factor-1 (IGF-1) on osteochondral tissue regeneration in a rabbit full-thickness osteochondral defect model. The four groups investigated included (i) a blank control (no GFs), (ii) GMP-loaded IGF-1 alone, (iii) GMP-loaded IGF-1 and gel-loaded TGF-β3, and (iv) GMP-loaded IGF-1 and GMP-loaded TGF-β3 in OPF composite hydrogels. The results of an in vitro release study demonstrated that TGF-β3 release kinetics could be modulated by the GF incorporation method. At 12 weeks post-implantation, the quality of tissue repair in both chondral and subchondral layers was analyzed based on quantitative histological scoring. All groups incorporating GFs resulted in a significant improvement in cartilage morphology compared to the control. Single delivery of IGF-1 showed higher scores in subchondral bone morphology as well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue when compared to a dual delivery of IGF-1 and TGF-β3, independent of the TGF-?3 release kinetics. The results suggest that although the dual delivery of TGF-β3 and IGF-1 may not synergistically enhance the quality of engineered tissue, the delivery of IGF-1 alone from bilayered composite hydrogels positively affects osteochondral tissue repair and holds promise for osteochondral tissue engineering applications.Item Polymer-Based Approaches to Bone Tissue Repair and Regeneration(2014-04-03) Henslee, Allan; Kasper, F. Kurtis; Mikos, Antonios G.; Zygourakis, Kyriacos; Wong, Mark E.; Ludwig, Joseph A.; Bennett, George N.The loss or damage of bone tissue due to trauma or surgical resection remains a significant clinical challenge. Limitations associated with the current gold standard of care, autografting, include donor site morbidity and an inherent lack of availability; thus prompting the need for alternative therapies and materials. Poly(propylene fumarate) (PPF) is a synthetic polymer that has previously been explored for bone tissue engineering applications. In this work, the properties of various formulations of PPF were optimized for specific clinical applications. Initially, a composite scaffold comprised of a solid PPF intramedullary rod and porous sleeve was evaluated in a segmental rat femoral defect model. The presence of the scaffold was able to increase the mechanical stability of the defect but also may have acted as a physical barrier to bone formation. In accordance with these results and through interactions with clinical collaborators, subsequent formulations of PPF targeted bony fractures and defects of the mandible. Key formulation parameters of PPF were varied in order to develop constructs with handling and mechanical properties suitable for mandibular fracture repair applications. Further consideration of the clinical relevancy of PPF-based materials led to the development of PPF as an analog to FDA-approved poly(methyl methacrylate) (PMMA)-based bone cement products. It was found that introducing crosslinked PPF particles to a liquid PPF phase could reduce the maximum crosslinking temperature as well as produce setting and handling characteristics comparable to that of current PMMA-based products. Lastly, as the development of biomaterials must continually adapt to fulfill changing clinical needs, a clinically focused project was performed in which porous PMMA-based implants were fabricated, characterized, and implanted under physician direction. Although successful, the limitations of PMMA including its non-degradable nature and the potential for bacterial contamination led to the development of degradable, porous PPF constructs capable of local antibiotic delivery for craniofacial applications. Properties of interest including degradation, porosity change over time, and antibiotic release kinetics were found to be suitable for craniofacial applications. The studies described here showcase the range of clinical applications that may be fulfilled by PPF-based materials.Item Repair of complex ovine segmental mandibulectomy utilizing customized tissue engineered bony flaps(Public Library of Science, 2023) Watson, Emma; Pearce, Hannah A.; Hogan, Katie J.; Dijk, Natasja W.M. van; Smoak, Mollie M.; Barrios, Sergio; Smith, Brandon T.; Tatara, Alexander M.; Woernley, Timothy C.; Shum, Jonathan; Pearl, Craig B.; Melville, James C.; Ho, Tang; Hanna, Issa A.; Demian, Nagi; Beucken, Jeroen J.J.P. van den; Jansen, John A.; Wong, Mark E.; Mikos, Antonios G.Craniofacial defects require a treatment approach that provides both robust tissues to withstand the forces of mastication and high geometric fidelity that allows restoration of facial architecture. When the surrounding soft tissue is compromised either through lack of quantity (insufficient soft tissue to enclose a graft) or quality (insufficient vascularity or inducible cells), a vascularized construct is needed for reconstruction. Tissue engineering using customized 3D printed bioreactors enables the generation of mechanically robust, vascularized bony tissues of the desired geometry. While this approach has been shown to be effective when utilized for reconstruction of non-load bearing ovine angular defects and partial segmental defects, the two-stage approach to mandibular reconstruction requires testing in a large, load-bearing defect. In this study, 5 sheep underwent bioreactor implantation and the creation of a load-bearing mandibular defect. Two bioreactor geometries were tested: a larger complex bioreactor with a central groove, and a smaller rectangular bioreactor that were filled with a mix of xenograft and autograft (initial bone volume/total volume BV/TV of 31.8 ± 1.6%). At transfer, the tissues generated within large and small bioreactors were composed of a mix of lamellar and woven bone and had BV/TV of 55.3 ± 2.6% and 59.2 ± 6.3%, respectively. After transfer of the large bioreactors to the mandibular defect, the bioreactor tissues continued to remodel, reaching a final BV/TV of 64.5 ± 6.2%. Despite recalcitrant infections, viable osteoblasts were seen within the transferred tissues to the mandibular site at the end of the study, suggesting that a vascularized customized bony flap is a potentially effective reconstructive strategy when combined with an optimal stabilization strategy and local antibiotic delivery prior to development of a deep-seated infection.Item Two Stage Repair of Composite Craniofacial Defects with Antibiotic Releasing Porous Poly(methyl methacrylate) Space Maintainers and Bone Regeneration(2013-09-16) Spicer, Patrick; Mikos, Antonios G.; Kasper, Kurt; Grande-Allen, K. Jane; Bennett, George N.; Wong, Mark E.Craniofacial defects resulting from trauma and resection present many challenges to reconstruction due to the complex structure, combinations of tissues, and environment, with exposure to the oral, skin and nasal mucosal pathogens. Tissue engineering seeks to regenerate the tissues lost in these defects; however, the composite nature and proximity to colonizing bacteria remain difficult to overcome. Additionally, many tissue engineering approaches have further hurdles to overcome in the regulatory process to clinical translation. As such these studies investigated a two stage strategy employing an antibiotic-releasing porous polymethylmethacrylate space maintainer fabricated with materials currently part of products approved or cleared by the United States Food and Drug Administration, expediting the translation to the clinic. This porous space maintainer holds the bone defect open allowing soft tissue to heal around the defect. The space maintainer can then be removed and one regenerated in the defect. These studies investigated the individual components of this strategy. The porous space maintainer showed similar soft tissue healing and response to non-porous space maintainers in a rabbit composite tissue defect. In humans, the porous space maintainers were well tolerated and maintained a soft tissue envelope for closure after implantation of a bone regeneration technology. The antibiotic-releasing space maintainers showed release of antibiotics from 1-5 weeks, which could be controlled by loading and fabrication parameters. In vivo, space maintainers releasing a high dose of antibiotics for an extended period of time increased soft tissue healing over burst release space maintainers in an infected composite tissue defect model in a rabbit mandible. Finally, stabilization of bone defects and regeneration could be improved through scaffold structures and delivery of a bone forming growth factor. These studies illustrate the possibility of the two stage strategy for repair of composite tissue defects of the craniofacial complex.