ABSTRACT
We estimated the predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) for blood, bone, and soft-tissue cultures. The specificities were 88.8%, 88.5%, and 92.7% for all cultures, blood cultures, and bone and soft-tissue cultures respectively, and the negative predictive values were 99.3%, 99.8%, and 92.7% respectively.
ABSTRACT
BACKGROUND: Culturing cells as cell spheres results in a tissue-like environment that drives unique cell phenotypes, making it useful for generating cell populations intended for therapeutic use. Unfortunately, common methods that utilize static suspension culture have limited scalability, making commercialization of such cell therapies challenging. Our team is developing an allogeneic cell therapy for the treatment of lumbar disc degeneration comprised of discogenic cells, which are progenitor cells expanded from human nucleus pulposus cells that are grown in a sphere configuration. METHODS: We evaluate sphere production in Erlenmeyer, horizontal axis wheel, stirred tank bioreactor, and rocking bag format. We then explore the use of ramped agitation profiles and computational fluid dynamics to overcome obstacles related to cell settling and the undesired impact of mechanical forces on cell characteristics. Finally, we grow discogenic cells in stirred tank reactors (STRs) and test outcomes in vitro (potency via aggrecan production and identity) and in vivo (rabbit model of disc degeneration). RESULTS: Computation fluid dynamics were used to model hydrodynamic conditions in STR systems and develop statistically significant correlations to cell attributes including potency (measured by aggrecan production), cell doublings, cell settling, and sphere size. Subsequent model-based optimization and testing resulted in growth of cells with comparable attributes to the original static process, as measured using both in vitro and in vivo models. Maximum shear rate (1/s) was maintained between scales to demonstrate feasibility in a 50 L STR (200-fold scale-up). CONCLUSIONS: Transition of discogenic cell production from static culture to a stirred-tank bioreactor enables cell sphere production in a scalable format. This work shows significant progress towards establishing a large-scale bioprocess methodology for this novel cell therapy that can be used for other, similar cell therapies.
Subject(s)
Bioreactors , Hematopoietic Stem Cell Transplantation , Animals , Cell Culture Techniques , Cells, Cultured , RabbitsABSTRACT
Postoperative complications can be burdensome on both the patient and the surgeon. Attention in literature is often directed toward different forms of treatment and successful outcomes in surgery. The incentive of this article is to bring insight toward postoperative complications in rearfoot surgery, more specifically, the repair of the Achilles tendon with suture tape and suture anchors. This article directs attention to the recent reports on hypersensitivity reactions seen with the use of suture tape and nonabsorbable suture anchors and may encourage physicians to make patients aware of this potential complication when using these materials.
Subject(s)
Achilles Tendon/surgery , Postoperative Complications , Achilles Tendon/injuries , Aged , Foreign-Body Reaction/etiology , Foreign-Body Reaction/surgery , Humans , Hypersensitivity/etiology , Hypersensitivity/surgery , Male , Middle Aged , Rupture, Spontaneous , Surgical Tape/adverse effects , Surgical Wound Infection/etiology , Surgical Wound Infection/prevention & control , Suture Anchors/adverse effects , Tendinopathy/etiology , Tendinopathy/prevention & control , Venous Thrombosis/etiology , Venous Thrombosis/prevention & controlABSTRACT
Revision surgeries, as well as conversions from implants to arthrodesis, can present unique challenges to the foot and ankle surgeon. Proper perioperative planning assists in optimizing the outcome of the procedure. In general, some amount of bone loss and/or shortening of the first metatarsal takes place, leading to the need for augmenting the site with bone graft or a synthetic substitute. Fixation also plays a key role in obtaining a successful conversion. A solid construct combined with bone graft assists the foot and ankle surgeon in achieving an optimal outcome.
Subject(s)
Arthrodesis/instrumentation , Arthroplasty, Replacement/instrumentation , Hallux , Joint Prosthesis , Metatarsophalangeal Joint , Bone Transplantation , Female , Humans , Middle Aged , ReoperationABSTRACT
Revision hammertoe surgery can be extremely challenging for the foot and ankle surgeon given the scar tissue and available osseous and soft tissue. Although not a common procedure, lesser metatarsophalangeal joint arthrodesis is an option for the patient especially in lieu of an amputation. This article describes the current literature and the surgical technique for a lesser metatarsophalangeal joint arthrodesis.
Subject(s)
Arthrodesis , Hammer Toe Syndrome/surgery , Metatarsophalangeal Joint/surgery , Aged , Female , Humans , Middle Aged , ReoperationABSTRACT
This article reviews the basic anatomy and physiology of tendon healing and ways to use biologics with tendon surgery. Many different products have been used, and this article reviews the literature to distinguish what is still recommended or proven effective through research.
Subject(s)
Biological Products/therapeutic use , Tendon Injuries/surgery , Humans , Wound Healing/physiologyABSTRACT
The timely delivery of the most up-to-date medicines and drug products is essential for patients throughout the world. Successful scaling of the bioreactors used within the biopharmaceutical industry plays a large part in the quality and time to market of these products. Scale and topology differences between vessels add a large degree of complication and uncertainty within the scaling process. Currently, this approach is primarily achieved through extensive experimentation and facile empirical correlations, which can be costly and time consuming while providing limited information. The work undertaken in the current study demonstrates a more robust and complete approach using computational fluid dynamics (CFD) to provide potent multiparameter scalability, which only requires geometric and material properties before a comprehensive and detailed solution can be generated. The CFD model output parameters that can be applied in the scale-up include mass transfer rates, mixing times, shear rates, gas hold-up values, and bubble residence times. The authors examined three bioreactors with variable geometries and were able to validate them based on single-phase and multiphase experiments. Furthermore, leveraging the resulting CFD output information enabled the authors to successfully scale-up from a known 2kL to a novel and disparate 5kL single-use bioreactor in the first attempted cell culture. This multiparameter scaling approach promises to ultimately lead to a reduction in the time to market providing patients with earlier access to the most groundbreaking medicines.