Download Free Drug Delivery Systems For Musculoskeletal Tissues Book in PDF and EPUB Free Download. You can read online Drug Delivery Systems For Musculoskeletal Tissues and write the review.

The Social Security Administration (SSA) administers two programs that provide disability benefits: the Social Security Disability Insurance (SSDI) program and the Supplemental Security Income (SSI) program. SSDI provides disability benefits to people (under the full retirement age) who are no longer able to work because of a disabling medical condition. SSI provides income assistance for disabled, blind, and aged people who have limited income and resources regardless of their prior participation in the labor force. Both programs share a common disability determination process administered by SSA and state agencies as well as a common definition of disability for adults: "the inability to engage in any substantial gainful activity by reason of any medically determinable physical or mental impairment which can be expected to result in death or which has lasted or can be expected to last for a continuous period of not less than 12 months." Disabled workers might receive either SSDI benefits or SSI payments, or both, depending on their recent work history and current income and assets. Disabled workers might also receive benefits from other public programs such as workers' compensation, which insures against work-related illness or injuries occurring on the job, but those other programs have their own definitions and eligibility criteria. Selected Health Conditions and Likelihood of Improvement with Treatment identifies and defines the professionally accepted, standard measurements of outcomes improvement for medical conditions. This report also identifies specific, long-lasting medical conditions for adults in the categories of mental health disorders, cancers, and musculoskeletal disorders. Specifically, these conditions are disabling for a length of time, but typically don't result in permanently disabling limitations; are responsive to treatment; and after a specific length of time of treatment, improve to the point at which the conditions are no longer disabling.
DISCLOSURES. No disclosures. INTRODUCTION. Drug delivery systems that employ physiological stimuli to trigger delivery (e.g. temperature, pH, etc.) allow for strict control and on-demand provision of biological factors [1]. To date, few systems have employed the mechanical environment as means for activation [2]. Many tissues in the body, such as musculoskeletal tissues, sustain loading during day-to-day activities. Upon injury or degeneration, normal loading patterns can shift towards aberrant, supra-physiological levels, which can intensify damage and promote degeneration [3]. Delivering therapeutic molecules in response to tissue loading could therefore provide strict spatiotemporal control over provision of biomolecules and lead to better outcomes. To that end, we developed mechanically-activated microcapsules (MAMCs) for the release of factors upon loading [4-5]. To further expand upon the therapeutic and tunable properties of this approach, this study aimed to expand the suite of MAMCs using osmotic annealing, to characterize their activation profiles in 2D and 3D environments in response to static and cyclic loading, and to investigate MAMC stability over time in u201cphysiological-likeu201d incubations. METHODS. MAMCs were fabricated using a glass capillary microfluidic device as in [6]. The inner phase contained bovine serum albumin (BSA) and Alexafluor488-BSA for visualization while the middle phase contained poly(lactic co-glycolic) acid (PLGA) 85:15 and Nile Red for visualization. Osmotic annealing was performed by collecting MAMCs in solutions containing different NaCl molarities, after which MAMC dimensions were characterized via confocal microscopy (Fig 1, A). To analyze MAMC resistance to compressive loads, MAMCs were compressed between parallel plates at 0.5% strain/sec. at various loads and imaged post overnight incubation to visualize inner solution retention (Fig 2, A). To characterize MAMC response in 3D environments, MAMCs were embedded in 500kPa PEGDA hydrogels (19%w/v). Using a custom confocal mounted compression device [7], MAMC-containing hydrogels were compressed from 0-30% strain at 5% strain steps and imaged at each step to measure MAMC deformation (Fig 2, B). To determine MAMC resistance to cyclic loading, MAMC-containing hydrogels were loaded between parallel plates from 2-20% strain at 5Hz for different durations and imaged to assess inner solution retention (Fig 2, C). Finally, to investigate MAMC stability in u201cphysiological-likeu201d solutions, MAMCs were incubated in PBS, basal media, or bovine synovial fluid at 37oC for up to 2 weeks and imaged at 1, 7 and 14 days of incubation to analyze microcapsule inner solution retention. Normally distributed data was analyzed via one-way ANOVA followed by Tukeyu2019s Multiple Comparison post-hoc test while non-normal data was analyzed via one-way or two-way ANOVA followed by Dunnu2019s Multiple Comparison test or Bonferroni post-hoc test respectively. RESULTS. Osmotic annealing led to decreased MAMC diameters and increased shell thicknesses as a function of NaCl molarity in the collecting solution (Fig 1). It is important to note that utilizing a NaCl molarity of 1.2M did not allow microcapsules to form, suggesting there is an upper limit to the NaCl molarity that can be used for effective osmotic annealing. Direct compression of MAMCs demonstrated that higher NaCl molarities increased MAMC resistance to static loads (Fig 2, B). In 3D environments, increased annealing also decreased MAMC deformation during static compression and increased resistance to cyclic loading (Fig 2, C-D). Finally, annealed MAMCs remained stable in bovine synovial fluid over a 2-week incubation period in comparison to BSA MAMCs (Fig 3), indicating the process increases stability of MAMCs in physiological conditions. DISCUSSION. Osmotic annealing expanded our suite of MAMCs and created microcapsules that possessed higher resistance to static and dynamic compressive loads in 2D and 3D environments and greater stability in synovial fluid. The manufacturing process did not require alteration of any microfluidic parameters, which provided ease of fabrication. The large suite of MAMCs presented in this study could allow for on-demand delivery of molecules to musculoskeletal tissues in response to the loading on the tissue and the surrounding matrix stiffness, ultimately allowing for strict mechano-regulation of biomolecule presentation.SIGNIFICANCE. This novel fabrication method allows for a wide suite of MAMCs to be manufactured in a single run, yielding microcapsules with varying resistance to loads and stability in synovial fluid. This drug delivery system can be easily tuned to loading patterns and injury degree to promote the healing of musculoskeletal tissues. REFERENCES. [1] Kost+ Adv Drug Deliv Rev 2001, [2] Korin+ Science 2012, [3] Sun+ Ann NY Acad Sci 2010, [4] Mohanraj+ 2016 ORS Annual Meeting #282, [5] Mohanraj+ 2017 ORS Annual Meeting #1405, [6] Tu+ Langmuir 2012, [7] Farrell+ Eur Cells Mat 2012 ACKNOWLEDGEMENTS. This work is supported by R01 AR071340 grant.
Nanoengineering in Musculoskeletal Regeneration provides the reader an updated summary of the therapeutic pipeline—from biomedical discovery to clinical implementation—aimed at improving treatments for patients with conditions of the muscles, tendons, cartilage, meniscus, and bone. Regenerative medicine focuses on using stem cell biology to advance medical therapies for devastating disorders. This text presents novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in musculoskeletal regeneration. Content includes basic, translational, and clinical research addressing musculoskeletal repair and regeneration for the treatment of diseases and injuries of the skeleton and its associated tissues. Musculoskeletal degeneration and complications from injuries have become more prevalent as people live longer and increasingly participate in rigorous athletic and recreational activities. Additionally, defects in skeletal tissues may immobilize people and cause inflammation and pain. Musculoskeletal regeneration research provides solutions to repair, restore, or replace skeletal elements and associated tissues that are affected by acute injury, chronic degeneration, genetic dysfunction, and cancer-related defects. The goal of musculoskeletal regeneration medicine research is to improve quality of life and outcomes for people with musculoskeletal injury or degradation. Provides broad coverage in all research areas focused on the applications of nanotechnology in musculoskeletal regeneration Offers useful guidance for physician-scientists with expertise in orthopedics, regenerative medicine, bioengineering, biomaterials, nanoengineering, stem cell biology, and chemistry Serves as a practical reference for many disciplines, including bioengineering, biomaterials, tissue engineering, regenerative medicine, musculoskeletal regenerative medicine, and nanomedicine
Controlled-release drug-delivery systems enable efficient and defined administration of therapeutic agents to target tissues. However, ultimate drug distribution and pharmacologic effect are determined by target tissue pharmacokinetics. In muscular tissues, complex architecture that is further augmented by dynamic motion and contraction can alter the pharmacokinetics and deposition of locally delivered macromolecules. We developed a system and applied a quantitative schema to investigate the impact of controlled mechanical loads applied to skeletal and cardiac muscle tissue on intramuscular transport of locally delivered drug. In a series of studies, we examined how the interaction between architectural configuration and functional mechanics alters the transport of drugs across both physicochemical and binding properties. We correlated these pharmacokinetic effects with characteristic parameters in the physiologic range of the tissue to derive mechanistic insight into the fundamental structural and dynamic elements that underlie these effects. While previous studies have revealed the unilateral scaling of substrate uptake with mechanical influences, we elucidated an architecturally defined pharmacokinetic setpoint whereby maximal drug penetration corresponds with optimal muscle function. Our findings elucidate basic biologic design in muscle that optimizes the interface between tissue and its physical environment. The unique insights from our investigations have broad impact on current understanding of the pharmacokinetic influences of biologic form and function, and elucidate new clinical strategies for controlled release and local delivery of a wide range of therapeutic compounds to mechanically active tissues.
Steven A. Rosenberg, MD In the past two decades significant progress has quality of life. The use of local radiation therapy has occurred, in the management of patients with mus- had a profound impact on the ability to achieve local loskeletal cancers, that has improved both the survival control. Cooperation between surgeons and radiation and the quality of life of afflicted patients. Changes in therapists often results in the tailoring of surgical p- the management of these patients have mirrored cedures to maximize the combined application of these trends in the entire field of oncology. two effective treatment modalities. Although impact on The most significant change has been improvement overall survival has not been demonstrated due to the in the surgical techniques for the resection of musculo- addition of radiation therapy, important advances in skeletal cancers based on a detailed understanding of improving the quality of life of patients receiving this the anatomic features of each particular tumor site, as combined-modality treatment have been evident. well as an appreciation of the natural biology that affects A third change impacting on the survival of patients the local spread of these tumors. The current volume of with musculoskeletal cancers has been the aggressive Musculoskeletal Cancer Surgery: Treatment of Sarcomas and resection of metastatic deposits.
Collagen-Based Drug Delivery Systems for Tissue Engineering.
Implantable Drug Delivery Systems: Design, Applications, and Future Perspectives" by Dr. Sandip G. Badadhe offers a comprehensive overview of implantable drug delivery, covering design, materials, applications, challenges, and future prospects. It caters to researchers, healthcare professionals, and students, providing insights into various types of systems, materials used, and practical applications. With real-world case studies and recommendations for future research, it serves as a valuable resource in advancing this innovative field.
Nanocomposites for Musculoskeletal Tissue Regeneration discusses the advanced biomaterials scientists are exploring for use as tools to mimic the structure of musculoskeletal tissues. Bone and other musculoskeletal tissues naturally have a nanocomposite structure, therefore nanocomposites are ideally suited as a material for replacing and regenerating these natural tissues. In addition, biological properties such as biointegration and the ability to tailor and dope the materials make them highly desirable for musculoskeletal tissue regeneration. Provides a comprehensive discussion on the design and advancements made in the use of nanocomposites for musculoskeletal tissue regeneration Presents an In-depth coverage of material properties Includes discussions on polymers, ceramics, and glass
Multiscale Cell-Biomaterials Interplay in Musculoskeletal Tissue Engineering and Regenerative Medicine addresses the key concepts involved in the interactions between cells and biomaterials in the musculoskeletal tissue engineering and regenerative medicine field. The updated developments and challenges of the mechanisms/mechanobiology and structure-function properties of those interactions, as well as emerging technologies underlying tissue-engineered scaffolding, are carefully discussed. Lastly, cell engineering and cell-based therapies, growth factors/drugs properties, vascularization, immunomodulation are also outlined. Given the large number of musculoskeletal disorders and related injuries that can affect muscles, bones and joints and lead to severe complications of the neuromuscular system, it is imperative to develop new treatment strategies to delay or repair associated diseases and to promote optimal long-term health. Presents the fundamentals of the complex interplay of cells with biomaterials in musculoskeletal tissue engineering Includes coverage of stem cells and cell-based therapies, in vitro and in vivo models, nanotechnology, bioprinting, computational modeling, regulatory and clinical translation, and much more Written by global leaders in the field