AbstractBackgroundNucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs. Thus, this study assessed the effectiveness of four previously reported expulsion testing protocols; hula‐hoop (Protocol 1), adapted hula‐hoop (Protocol 2), eccentric cycling (Protocol 3), and ramp to failure (Protocol 4), applied to two NRDs, one preformed and one in situ curing.MethodsNucleus material was removed from 40 bovine tail intervertebral disks. A NRD was inserted posteriorly into each cavity and the disks were subjected to one of four expulsion protocols.ResultsNRD response was dependent on both the NRD design and the loading protocol. Protocol 1 resulted in higher migration and earlier failure rates compared to Protocol 2 in both NRDs. The preformed NRD was more likely to migrate when protocols incorporated rotation. The NRDs had equal migration (60%) and expulsion (60%) rates when using unilateral bending and ramp testing. Combining the results of multiple tests revealed complimentary information regarding the NRD response.ConclusionsAdapted hula‐hoop (Protocol 2) and ramp to failure (Protocol 4), combined with fluoroscopic analysis, revealed complimentary insights regarding migration and failure risk. Therefore, when adopting the surgical approach and animal model used in this study, it is recommended that NRD performance be assessed using both a cyclic and ramp loading protocol.

Purpose:To biomechanically compare primary medial patellofemoral ligament (MPFL) repair (MPFLr) augmented with a reinforced bioinductive implant (RBI) to the native MPFL ligament and a semitendinosus (semi-T) MPFL reconstruction (MPFLR) at time zero. Methods:Four fresh-frozen matched pair cadavers (8 knees) were used to biomechanically compare the native MPFL to augmented MPFLr (n = 4) and semi-T MPFLR (n = 4). The native MPFL (n = 8) was isolated, preserving the femoral and patellar attachments, and pulled to failure. The semi-T was harvested from 1 of the matched pairs and whipstitched, as was a 250-mm × 5-mm RBI. A standard double-bundle docking technique was utilized. The patella was potted and mechanically pulled parallel to the transverse axis until failure in both cohorts. Cyclic creep, load and displacement at failure, failure mode, and stiffness were recorded. Results:Failure load was highest in the RBI with repair group (287 ± 130 N) compared to the native MPFL (219 ± 64 N) and the semi-T group (84 ± 29 N). No statistically significant difference in failure load between the RBI augmentation with repair group and the native ligament (P = .19) were found. The semi-T reconstruction group failed at the least amount of displacement (7.93 ± 3.4 mm) compared to the native MPFL (20.9 ± 9 mm) (P < .01) and the RBI with repair group (33.2 ± 17.7 mm) (P < .02). At 10 mm of displacement, the RBI group (8.3 ± 1.2 N/mm) demonstrated stiffness in the midrange compared to the native MPFL (14.1 ± 7.1 N/mm). Early anchor/tendon pullout failure on the patella side was noted in the semi-T group compared to the RBI group. One reconstruction was excluded from analysis due to poor bone quality. Conclusions:No statistically significant difference was seen between the augmented MPFL repair and the native MPFL in load-to-failure testing. The augmented MPFL repair was observed to have biomechanical properties similar to the native MPFL. MPFLr with RBI augmentation provided consistent stiffness at clinically relevant displacement. Clinical Relevance:Primary MPFL repair and reconstruction using the semi-T graft, while effective, are nevertheless imperfect procedures. MPFL repair has been shown to have higher instability recurrence rates, while the stiffness profile of MPFLR with semi-T is higher than the native MFPL and may lead to knee stiffness, loss of motion, or cartilage damage. The results of this time-zero biomechanical study indicate that the use of an RBI for augmentation of a primary MPFL repair may be a viable alternative to traditional MPFL repair or reconstruction using a semi-T graft.

Primary challenges associated with the design and success of polymeric biomedical devices are generally related to the control of the biomaterial in terms of degradability characteristics, sufficient processability characteristics, and required mechanical strength that may be altered during sterilization or manufacturing procedures. Polyvinyl alcohol-based thermoresponsive biomaterials provide a distinct advantage for biomedical applications as their physiochemical properties can be easily modified according to their desired use. In this work, we evaluated the thermal degradation characteristics of a polyvinyl alcohol (PVA)/polyethylene glycol (PEG)/polyvinylpyrrolidone (PVP) hydrogel that undergoes a steam sterilization autoclave cycle at 121(degrees)C to induce fluid-like behavior. FTIR was used to characterize the evolution of the area of the carbonyl region between 1800 and 1525 cm(-1). The carbonyl area increased at temperatures beyond 121(degrees)C which were used to accelerate the onset of degradation during both thermal oxidation and pyrolysis. The change in the carbonyl region was shown to correlate with respect to both temperature and time of exposure. The carbonyl region increased significantly in the presence of oxygen at temperatures above 150(degrees)C. Despite showing signs of thermal degradation at temperatures exceeding 150(degrees)C, our biomaterial was shown to be stable at 121(degrees)C during thermal degradation testing. Furthermore, bulk property analysis showed the hydrogel's mechanical and swelling properties were preserved even after being subject to multiple autoclave cycles beyond what would be experienced during a sterilization or clinical procedure.

Purpose:To compare the pullout strength of a bio-inductive implant (BI) used to augment a medial patellofemoral ligament (MPFL) repair with the pullout strength of semitendinosus graft in a biomechanical cadaveric model.Methods:Six matched pairs of cadavers (12 knees) were used in the biomechanical testing comparing semitendinosus tendon (Semi-T) versus a BI. The Semi-T was harvested from 1 of the matched pairs. A standard double-bundle technique using 2 sockets in the upper two-thirds of the patella 15 mm apart was performed. After docking of the graft into the patella, the patella was dissected free of soft tissues and potted into a fixture to allow mechanical pull parallel to the transverse axis of the patella. The construct was pulled to failure.Results:There was no statistically significant difference in pullout strength (P = .77) between the BI group (249.3 ± 36.3 N) and Semi-T group (235.0 ± 113.6 N) double-bundle constructs. In the Semi-T group, 50% of the specimens (3 of 6 knees) failed via anchor pullout and a fourth specimen failed at the suture-anchor interface (16.7%), whereas in the BI group, 16.7% of the specimens (1 of 6 knees) failed by anchor pullout. Although the Semi-T group (49.5 ± 14.1 N/mm) showed significantly greater stiffness than the BI group (13.8 ± 0.6 N/mm, P < .01), pullout strength in the Semi-T group was highly variable: 50% of the specimens (3 of 6 knees) with semitendinosus constructs failed at 5 mm of displacement or less via graft or anchor pullout. Maximum load, displacement at failure, stiffness, and load at 5 mm were compared between the augmented and non-augmented control specimens using a 2-tailed non-equal variance Student t test. For all comparisons, P < .05 was considered to indicate a statistically significant difference.Conclusions:In this biomechanical study, augmentation of an MPFL reconstruction using a common double-bundle technique with a BI had the same pullout strength as a semitendinosus graft using the same technique in cadaveric knees.Clinical Relevance:MPFL repair after a patellar dislocation may be inadequate to restore the strength of the native MPFL and prevent recurrent patellar instability. Recurrent instability of the patella can result in progressive injury to the soft tissue and articular cartilage of the patella and femur. It is important to study the techniques used for MPFL repair to continually improve patient outcomes. Further testing of these additional techniques and clinical studies are needed to evaluate the implants used to augment MPFL repairs.

Injectable polymers offer great benefits compared to other types of implants; however, they tend to suffer from increased mechanical wear and may need a replacement implant to restore these mechanical properties. The purpose of this experiment is to investigate an injectable hydrogel's self-healing ability to augment itself to a previously molded implant. This was accomplished by performing a tensile strength test to examine potential diminishing mechanical properties with increasing time, as well as dye penetration tests to examine the formation of interfacial bonds between healed areas of hydrogels. There were several time points in between injections that were explored, from 0 min between injections all the way up to 48 h in between injections. The tests showed no statistical differences of the increased injection times compared to the single injection for the tensile test. However, our results showed an increase of mechanical breaks at self-healed joints, as well as a linear regression test showed a decrease in dye diffusion rate as time between injections increase. These results show that the hydrogel has strong self-healing abilities, and as time between injections increase, they mechanical properties will slowly decrease. Based on this, the tests can be applied to other injectable implants and a noninvasive solution to a worn-down implant, as well as show scientific backing to a possibly unique and beneficial self-healing property.

Background The “no‐reflow phenomenon” compromises percutaneous coronary intervention outcomes. There is an unmet need for a device that prevents no‐reflow phenomenon. Our goal was to develop a guidewire platform comprising a nondisruptive hydrophilic coating that allows continuous delivery of adenosine throughout a percutaneous coronary intervention. Methods and Results We developed a guidewire with spaced coils to increase surface area for drug loading. Guidewires were plasma treated to attach hydroxyl groups to metal surfaces, and a methoxy–polyethylene glycol–silanol primer layer was covalently linked to hydroxyl groups. Using polyvinyl alcohol, polyvinyl pyrrolidone, and polyvinyl acetate, a drug layer containing jet‐milled adenosine was hydrogen‐bonded to the polyethylene glycol–silanol layer and coated with an outer diffusive barrier layer. Coatings were processed with a freeze/thaw curing method. In vitro release studies were conducted followed by in vivo evaluation in pigs. Coating quality, performance, and stability with sterilization were also evaluated. Antiplatelet properties of the guidewire were also determined. Elution studies with adenosine‐containing guidewires showed curvilinear and complete release of adenosine over 60 minutes. Porcine studies demonstrated that upon insertion into a coronary artery, adenosine‐releasing guidewires induced immediate and robust increases (2.6‐fold) in coronary blood flow velocity, which were sustained for ≈30 minutes without systemic hemodynamic effects or arrhythmias. Adenosine‐loaded wires prevented and reversed coronary vasoconstriction induced by acetylcholine. The wires significantly inhibited platelet aggregation by >80% in vitro. Guidewires passed bench testing for lubricity, adherence, integrity, and tracking. Conclusions Our novel drug‐releasing guidewire platform represents a unique approach to prevent/treat no‐reflow phenomenon during percutaneous coronary intervention.

BACKGROUND CONTEXT Intervertebral disc (IVD) degeneration (IVDD) is implicated as a cause of low back pain. The earliest degenerative changes typically occur in the central nucleus pulposus (NP), where progressive loss of proteoglycans and associated hydration compromise tissue mechanical function. PURPOSE We developed a noncrosslinked injectable hydrogel for NP replacement and augmentation together with its percutaneous delivery method and instrument assembly. We then evaluated the short- and long-term performance of this hydrogel in a goat model of moderate IVDD. Methods Six goats underwent two percutaneous procedures: one to induce degeneration in 3 lumbar IVDs via injection of 1U C-ABC and, 2 weeks later, a second procedure for the delivery of hydrogel at 2 levels with the third remaining untreated. Animals were euthanized at 6 weeks (n=2) and 12 weeks (n=1); three animals are currently enrolled for long-term survival. Disc height index (DHI) was measured from monthly lateral radiographs in the standing animal. Postmortem, motion segments were imaged using microcomputed tomography (µCT) to assess hydrogel distribution and bone volume fraction values (BV/TV) for cranial and caudal endplates. Volumetric analysis and compression testing were performed on explanted gels. Samples were dried to determine polymer and water content. Explant characteristics were compared to nonimplanted gels. Histology was performed to assess glycosaminoglycans and collagen content, cellularity, and disc morphology. Significant changes in DHI were established using Wilcoxon matched-pairs signed ranks tests and differences in histological grades were established using Kruskal-Wallis test with post-hoc Dunn's tests (p<0.05). Results Animals recovered uneventfully from surgical procedures. Extrusion of hydrogel into the spinal canal during delivery occurred in two animals without major clinical repercussions. At 2 weeks after C-ABC injection, DHI was ∼80% of pre-C-ABC levels. For IVDs treated with hydrogel, DHI improved while untreated IVDs continued to degenerate. The hydrogel presents radiographically unremarkable for up to 2 years post nucleoplasty. µCT imaging demonstrated that the majority of hydrogel was localized to the central NP. BV/TV ratio of treated levels at 6-week and 12-week endpoint were similar to controls. Explant analyses showed higher elastic moduli and polymer content compared to nonimplanted gels. Treated IVDs exhibited an overall improved histological grade compared to positive controls. Conclusions The results of this work illustrate the practical utility of an injectable hydrogel being effective in normalizing the mechanical function of the degenerating IVD in a clinically relevant animal model. The implant showed successful retention without extrusion following delivery. A critical benchmark for the success of any injectable implant to treat IVDD is the normalization of mechanical properties. We demonstrate through long-term in vivo follow up studies that hydrogel injected into degenerating goat discs can preserve the spine motion segment. There is a critical need for new therapies for patients with symptomatic disc degeneration that preserve joint mobility. A minimally invasive injectable therapy mitigates anulus fibrosus trauma during nucleoplasty and may restore the biomechanics of the motion segment. Moreover, successful biomechanical restoration of the affected motion segment may slow or prevent further IVDD. Motion preservation therapies may also help mitigate adjacent level IVDD in these patient cohorts. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs. Intervertebral disc (IVD) degeneration (IVDD) is implicated as a cause of low back pain. The earliest degenerative changes typically occur in the central nucleus pulposus (NP), where progressive loss of proteoglycans and associated hydration compromise tissue mechanical function. We developed a noncrosslinked injectable hydrogel for NP replacement and augmentation together with its percutaneous delivery method and instrument assembly. We then evaluated the short- and long-term performance of this hydrogel in a goat model of moderate IVDD. Six goats underwent two percutaneous procedures: one to induce degeneration in 3 lumbar IVDs via injection of 1U C-ABC and, 2 weeks later, a second procedure for the delivery of hydrogel at 2 levels with the third remaining untreated. Animals were euthanized at 6 weeks (n=2) and 12 weeks (n=1); three animals are currently enrolled for long-term survival. Disc height index (DHI) was measured from monthly lateral radiographs in the standing animal. Postmortem, motion segments were imaged using microcomputed tomography (µCT) to assess hydrogel distribution and bone volume fraction values (BV/TV) for cranial and caudal endplates. Volumetric analysis and compression testing were performed on explanted gels. Samples were dried to determine polymer and water content. Explant characteristics were compared to nonimplanted gels. Histology was performed to assess glycosaminoglycans and collagen content, cellularity, and disc morphology. Significant changes in DHI were established using Wilcoxon matched-pairs signed ranks tests and differences in histological grades were established using Kruskal-Wallis test with post-hoc Dunn's tests (p<0.05). Animals recovered uneventfully from surgical procedures. Extrusion of hydrogel into the spinal canal during delivery occurred in two animals without major clinical repercussions. At 2 weeks after C-ABC injection, DHI was ∼80% of pre-C-ABC levels. For IVDs treated with hydrogel, DHI improved while untreated IVDs continued to degenerate. The hydrogel presents radiographically unremarkable for up to 2 years post nucleoplasty. µCT imaging demonstrated that the majority of hydrogel was localized to the central NP. BV/TV ratio of treated levels at 6-week and 12-week endpoint were similar to controls. Explant analyses showed higher elastic moduli and polymer content compared to nonimplanted gels. Treated IVDs exhibited an overall improved histological grade compared to positive controls. The results of this work illustrate the practical utility of an injectable hydrogel being effective in normalizing the mechanical function of the degenerating IVD in a clinically relevant animal model. The implant showed successful retention without extrusion following delivery. A critical benchmark for the success of any injectable implant to treat IVDD is the normalization of mechanical properties. We demonstrate through long-term in vivo follow up studies that hydrogel injected into degenerating goat discs can preserve the spine motion segment. There is a critical need for new therapies for patients with symptomatic disc degeneration that preserve joint mobility. A minimally invasive injectable therapy mitigates anulus fibrosus trauma during nucleoplasty and may restore the biomechanics of the motion segment. Moreover, successful biomechanical restoration of the affected motion segment may slow or prevent further IVDD. Motion preservation therapies may also help mitigate adjacent level IVDD in these patient cohorts.

Hip implants are extremely common procedures that are performed to relieve pain and restore function to the hip joint. Historically, most implants would last for the duration of the patient’s life, approximately 15 years after implantation; however, due to medical advancements patients are living longer and outliving the life of their implant. The most common cause for implant failure is the failure of the bond between the implant and the bone, occurring due to the translation or rotation of the implant. Once an implant has failed, a very invasive, costly, and painful revision surgery is required. There is significant advantage in the early detection of implant loosening. This paper presents a radial basis function based image processing technique to detect minute 3-D rotations of a hip implant from 2-D X-ray images. Comparing these rotations for a particular hip implant over time can alert orthopedic surgeons of trends that might lead to impending gross loosening of the implant and enable early correction.

ABSTRACTCrystallite regions within a hydrogel network contribute to its mechanical strength, which is crucial for use in load‐bearing applications. However, high amounts of crystallinity can negatively impact the ability for hydrogels to be injected, an attractive property that could replace the need for highly invasive surgical procedures. The reversibility of crystallinity and its lasting impact on the injectability of poly(vinyl alcohol) and poly(ethylene glycol) hydrogels was evaluated in this paper. The relative percent crystallinity in hydrogels was evaluated after storage and autoclaving in syringes in weekly intervals using X‐ray diffraction. Results indicate that crystallinity increased over time and significantly decreased after autoclaving for all samples, where postautoclaved samples contained comparable crystallinity percentages to freshly made gels (p > 0.05). Injectability was evaluated using calculated viscosity. Aged samples were able to be injected after autoclaving, yet there was no determination established between viscosity and storage times based on the data. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48706.

Hospitals are spending an average of $36.5 billion annually due to nosocomial infections[1]. Nosocomial infections are illnesses patients acquire during their stay at the hospital. These infections can be spread through direct patient contact, improper hand washing, airborne vectors, and contaminated medical equipment. When following proper sterilization protocol, multi-dose vials demonstrated insignificant bioburden. If proper aseptic technique is compromised, multi-dose vials are susceptible to housing nosocomial infectious agents. Recently, multi-dose medication vials have shown to be sources of bacterial infection, with randomized testing showing that 4.2% of previously-used vials tested positive for bacteria[2]. While proper aseptic handling of these vials can successfully and adequately prevent the spread of infections, studies have shown that poor aseptic techniques are common causes of contamination[3, 4]. Furthermore, in one survey, 34% of anesthesiologists stated that they never or rarely disinfect the hub of these vials prior to use[5]. They are monetary and qualitatively costly because the patient’s health is now at risk, increasing their odds of death nearly 6-fold compared to a patient without a nosocomial infection[8]. Despite established protocols in the hospital, these methods can sometimes fail in practice during both routine injections and high-stress emergencies. These observations demonstrate the need for sterilization methods that are less prone to user error or negligence. The goal of this project is to design a novel device to that curtails user error involving multi dose vials and reduces the risk of nosocomial infections. The design encompasses an improved physical barrier that better prevents bacterial migration, and a built-in chemical barrier that would eliminate human error of standardized disinfecting protocols. The prototype has to be functional, sturdy, and efficient, as it will sometimes be used in emergency situations. The project utilizes a wide range of testing involving the evaluations of multi dose vials and the prototype for the product. Isopropyl alcohol (IPA) evaporation tests were used to estimate the shelf life of the prototype. Dye ingress testing was conducted to analyze whether microorganisms could infiltrate the inside of the vial. The results of the dye ingress test showed there was no evidence of infiltration into the tested vials. A contamination and disinfection protocol was developed to prove that infection causing microorganisms are transferred from the vial hub to the sterile needle that is then being injected into the patient. The results of the disinfection testing confirmed this hypothesis, providing a further need for this cap design. Early prototype development provided promising results that showed disinfection of the vial hub after direct contamination. Utilizing the technology of 3D printing, the team hopes to produce a marketable disinfecting cap that can reduce human error during injections.

Oral administration of monoclonal antibodies (mAbs) may enable the localized treatment of infections or other conditions in the gastrointestinal tract (GI) as well as systemic diseases. As with the development of oral protein biotherapeutics, one of the most challenging tasks in antibody therapies is the loss of biological activity due to physical and chemical instabilities. New families of complexation hydrogels with pH-responsive properties have demonstrated to be excellent transmucosal delivery vehicles. This contribution focuses on the design and evaluation of hydrogel carriers that will minimize the degradation and maximize the in vivo activity of anti-TNF-α, a mAb used for the treatment of inflammatory bowel disease (IBD) in the GI tract and systemically for the treatment of rheumatoid arthritis. P(MAA-g-EG) and P(MAA-co-NVP) hydrogels systems were optimized to achieve adequate swelling behavior, which translated into improved protein loading and release at neutral pH simulating the small intestine conditions. Additionally, these hydrogel systems preserve antibody bioactivity upon release resulting in the systemic circulation of an antibody capable of effectively performing its biological function. The compatibility if these hydrogels for mAb bioactivity preservation and release makes them candidates for use as oral delivery systems for therapeutic antibodies.

Administering therapeutics through the oral route or to the central nervous system presents significant challenges for large-molecule drugs, primarily due to the diffusive barriers and efflux mechanisms present in the cellular lining of the gastrointestinal (GI) tract and blood brain barrier (BBB). Receptor-mediated endocytosis (RME) has been extensively studied as a method for augmenting the transport of therapeutic devices across these barriers. These devices range from simple ligand-therapeutic conjugates to complex ligand-nanoparticle systems. Customarily, characterizing the uptake of these carriers relies on their comparisons to the native therapeutic, which provides no understanding of ligand or cellular performance. Therefore, the focus of this research is to investigate the transport potential of the RME pathway itself, so that ligands can act as suitable benchmarks for success.To better understand the pharmacokinetics of the RME pathway, a model for barrier transport was designed based on the endocytosis cycle of transferrin, a ligand often used in RME drug-delivery research. This model established the correlation between apical receptor concentration and maximum transport capability. Experimental studies confirmed this relationship, demonstrating an upper transport limit independent of the applied dose. This contrasts with the dose-proportional pathways native therapeutics rely on for transport. Thus, the direct comparison of these two transport mechanisms can produce misleading results that change with arbitrarily chosen doses. Furthermore, transport potential was hindered by repeated use of the RME-cycle.Commonly, nanoparticles are incorporated to amplify the payload capacity of RME-devices despite the burden they pose to the cell. The response of size and the size distribution of nanoparticle-ligand formulations on the cell were tested and contrasted to their increasing payloads. These results demonstrate that size has a major influence on nanoparticle transport, and future studies should base the success of this technology not on the performance of the therapeutic itself, but on the capabilities of the cell. Using receptor-binding studies, we were able to demonstrate how these capabilities can be predicted and potentially adopted for high-throughput screening methods.%%%%Ph.D., Chemical Engineering – Drexel University, 2014

Receptor-mediated endocytosis (RME) has been extensively studied as a method for augmenting the transport of therapeutic devices across monolayers. These devices range from simple ligand-therapeutic conjugates to complex ligand-nanocarrier systems. However, characterizing the uptake of these carriers typically relies on their comparisons to the native therapeutic, which provides no understanding of the ligand or cellular performance. To better understand the potential of the RME pathway, a model for monolayer transport was designed based on the endocytosis cycle of transferrin, a ligand often used in RME drug-delivery devices. This model established the correlation between apical receptor concentration and transport capability. Experimental studies confirmed this relationship, demonstrating an upper transport limit independent of the applied dose. This contrasts with the dose-proportional pathways that native therapeutics rely on for transport. Thus, the direct comparison of these two transport mechanisms can produce misleading results that change with arbitrarily chosen doses. Furthermore, transport potential was hindered by repeated use of the RME cycle. Future studies should base the success of this technology not on the performance of the therapeutic itself, but on the capabilities of the cell. Using receptor-binding studies, we were able to demonstrate how these capabilities can be predicted and potentially adopted for high-throughput screening methods.

Receptor-mediated pathways offer the ability to transport therapeutics across cellular monolayers that would otherwise block them. However, current characterization methods have been found to be inadequate in their ability to adequately describe the full benefit of these drug delivery systems. In this report, we describe a novel way to define their transport using receptor-ligand kinetic models.

Polymeric nanomaterials have the potential to improve upon present chemotherapy delivery methods. They successfully reduce side effects while increasing dosage, increase residence time in the body, offer a sustained and tunable release, and have the ability to deliver multiple drugs in one carrier. However, traditional nanomaterial formulations have not produced highly therapeutic formulations to date due to their passive delivery methods and lack of rapid drug release at their intended site. In this paper, we have focused on a few “smart” technologies that further enhance the benefits of typical nanomaterials. Temperature and pH-responsive drug delivery devices were reviewed as methods for triggering release of encapsulating drugs, while aptamer and ligand conjugation were discussed as methods for targeted and intracellular delivery, with emphases on in vitro and in vivo works for each method.

and statement of qualifications. Finalists are interviewed by the course faculty advisors, and positions are offered to match the number of available projects. Projects are submitted and recruited from partnering clinicians and industrial partners, as well as biomedical engineering start-up companies in the area. All projects are then vetted carefully by Biomedical Engineering faculty for scope, feasibility, and academic potential. The final project list is developed based on the student enrollment and perceived potential of the projects. Team Leaders are provided with a description of each available project and asked to rank their choices. The course faculty advisors then optimize the matching to provide one Team Leader per project. A similar matching process occurs for the non-Leader students in the course.