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4. Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment

Author

Vinikoor, Tra, Dzidotor, Godwin K., Le, Thinh T., Liu, Yang, Kan, Ho-Man, Barui, Srimanta, Chorsi, Meysam T., Curry, Eli J., Reinhardt, Emily, Wang, Hanzhang, Singh, Parbeen, Merriman, Marc A., D’Orio, Ethan, Park, Jinyoung, Xiao, Shuyang, Chapman, James H., Lin, Feng, Truong, Cao-Sang, Prasadh, Somasundaram, Chuba, Lisa, Killoh, Shaelyn, Lee, Seok-Woo, Wu, Qian, Chidambaram, Ramaswamy M., Lo, Kevin W. H., Laurencin, Cato T., and Nguyen, Thanh D.

Published
2023
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14. Hyaluronic acid–British anti-Lewisite as a safer chelation therapy for the treatment of arthroplasty-related metallosis

Author

Ude, Chinedu C., primary, Schmidt, Stephen J., additional, Laurencin, Samuel, additional, Shah, Shiv, additional, Esdaille, Jayson, additional, Kan, Ho-Man, additional, Holt, Brian D., additional, Arnold, Anne M., additional, Wolf, Michelle E., additional, Nair, Lakshmi S., additional, Sydlik, Stefanie A., additional, and Laurencin, Cato T., additional

Published
2023
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19. Biomimetic Electroconductive Nanofibrous Matrices for Skeletal Muscle Regenerative Engineering

Author

Tang, Xiaoyan, Saveh-Shemshaki, Nikoo, Kan, Ho-Man, Khan, Yusuf, and Laurencin, Cato T.

Abstract

Background: The regeneration of the muscles of the rotator cuff represents a grand challenge in musculoskeletal regenerative engineering. Several types of matrices have been proposed for skeletal muscle regeneration. However, biomimetic matrices to promote muscle regeneration and mimic native muscle tissue have not been successfully engineered. Besides topographical cues, an electrical stimulus may serve as a critical cue to improve interactions between materials and cells in scenarios fostering muscle regeneration. In this in vitro study, we engineered a novel stimulus-responsive conductive nanocomposite matrix and studied its ability to regulate muscle cell adhesion, proliferation, and differentiation. Electroconductive nanocomposite matrices demonstrated tunable conductivity and biocompatibility. Under the optimum concentration of conductive material, the matrices facilitated muscle cell adhesion, proliferation, and differentiation. Importantly, aligned conductive fibrous matrices were effective in promoting myoblast differentiation by upregulation of myogenic markers. The results demonstrated a promising potential of aligned conductive fibrous matrices for skeletal muscle regenerative engineering. Lay Summary: Around 40% of the human body mass consists of skeletal muscle. Musculoskeletal disorders such as muscle atrophy and fatty infiltration after rotator cuff injury lead to disability and pain and increase the rate of retear after rotator cuff surgery. The study showed the potential of novel engineered matrix to regenerate skeletal muscle by utilizing conductive material and nanofiber-based matrices. The incorporation of conductive material and aligned nanofibers as electrical and topographical cues significantly impacted cell viability and differentiation to support muscle regeneration. Future Work: The study demonstrated that electroconductive nanocomposite matrix can favorably modulate myoblast proliferation and differentiation. Future study will investigate the in vivo efficacy of the engineered matrix using a rat rotator cuff tear model to understand the ability of the engineered matrix in reducing the fatty infiltration.

Published
2024
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27. Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits

Author

Liu, Yang, primary, Dzidotor, Godwin, additional, Le, Thinh T., additional, Vinikoor, Tra, additional, Morgan, Kristin, additional, Curry, Eli J., additional, Das, Ritopa, additional, McClinton, Aneesah, additional, Eisenberg, Ellen, additional, Apuzzo, Lorraine N., additional, Tran, Khanh T. M., additional, Prasad, Pooja, additional, Flanagan, Tyler J., additional, Lee, Seok-Woo, additional, Kan, Ho-Man, additional, Chorsi, Meysam T., additional, Lo, Kevin W. H., additional, Laurencin, Cato T., additional, and Nguyen, Thanh D., additional

Published
2022
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35. A Single Administration of Synthetic Artificial Stem Cells (SASC) Attenuates Osteoarthritis Progression

Author

Shah, Shiv, Bhattacharjee, Maumita, Kan, Ho-Man, Marchini, Rachel L., Schmidt, Tannin A., Nair, Lakshmi S., and Laurencin, Cato T.

Abstract

Purpose : Osteoarthritis (OA) is a highly prevalent joint disease for which common therapies may provide symptomatic relief but have failed to provide a curative solution. There has been a growing interest in disease-modifying therapies, such as the use of stem cells and bioactive factors in treating OA. The synthetic artificial stem cell (SASC) system has previously been introduced as one such disease-modifying therapy: designed to mimic the paracrine effect of biological stem cells but with the added ability to engineer the composition and tailor it to different tissue types. Methods: In the present study, the efficacy of a single intra-articular injection was evaluated across three doses (1, 3, or 5 million) of SASC cells in a collagenase-induced OA rat model. Inflammation was monitored by joint swelling through the 63 day treatment period and structural and functional cartilage regeneration outcomes as well as local immune and inflammatory outcomes were evaluated by histology, nano-indentation of the gross cartilage, and immunohistochemistry. Further, in vitroSASC modulation of the NF-κβ pathway was observed by monitoring various upstream and downstream gene expression profiles along the pathway. Results: A single administration of 3 million and 5 million SASC cells reduced knee swelling attenuates cartilage degeneration as observed by Safranin O staining, compared to the OA control. Further, major genes along the NF-κβ pathway were significantly modulated by SASC to a similar extent compared to ADSC control. Conclusion: The present study demonstrated that SASC Cells have a dose-dependent response in attenuating collagenase-induced OA progression and effectively modulates the major inflammatory pathway involved in the pathogenesis of OA. Lay Summary: In this study, we investigated the efficacy of synthetic artificial stem cells (SASC) in treating osteoarthritis (OA). Different doses of SASC cells were injected into rats with OA. Higher doses of SASC cells reduced knee swelling, protected against cartilage degeneration, and modulated the inflammatory NF-κβ pathway. This work highlights potential of SASC cells as a curative treatment for OA.

Published
2023
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37. Tau-dependent microtubule disassembly initiated by prefibrillar [beta]-amyloid

Author

King, Michelle E., Kan, Ho-Man, Baas, Peter W., Erisir, Alev, Glabe, Charles G., and Bloom, George S.

Subjects
Alzheimer's disease -- Research, Cytology -- Research, Amyloid beta-protein -- Research, Biological sciences
Abstract

Alzheimer's Disease (AD) is defined histopathologically by extracellular [beta]-amyloid (A[beta]) fibrils plus intraneuronal tau filaments. Studies of transgenic mice and cultured cells indicate that AD is caused by a pathological cascade in which A[beta] lies upstream of tau, but the steps that connect A[beta] to tau have remained undefined. We demonstrate that tau confers acute hypersensitivity of microtubules to prefibrillar, extracellular A[beta] in nonneuronal cells that express transfected tau and in cultured neurons that express endogenous tau. Prefibrillar A[beta]42 was active at submicromolar concentrations, several-fold below those required for equivalent effects of prefibrillar A[beta]40, and microtubules were insensitive to fibrillar A[beta]. The active region of tau was localized to an N-terminal domain that does not bind microtubules and is not part of the region of tau that assembles into filaments. These results suggest that a seminal cell biological event in AD pathogenesis is acute, tau-dependent loss of microtubule integrity caused by exposure of neurons to readily diffusible A[beta].

Published
2006

46. Cytoplasmic dynein associated peptide-linked nanoparticles for non-viral vector applications

Author

Kan Ho Man, Carbone Ercia, Lo Wai Hong, Rajpura Komal, and Jiang Tao

Subjects
chemistry.chemical_classification, Cytoplasmic dynein, Histology, Chemistry, Biomedical Engineering, Nanoparticle, Bioengineering, Peptide, 02 engineering and technology, 021001 nanoscience & nanotechnology, 030226 pharmacology & pharmacy, Cell biology, Viral vector, 03 medical and health sciences, 0302 clinical medicine, Dynactin, 0210 nano-technology, Biotechnology
Published
2016

48. One-day Treatment of Small Molecule 8-Bromo-cyclic AMP Analogue Induces Cell-based VEGF production for In Vitro Angiogenesis and Osteoblastic Differentiation

Author

Lo, Kevin W.-H., Kan, Ho Man, Gagnon, Keith A., and Laurencin, Cato T.

Subjects
Vascular Endothelial Growth Factor A, Mice, Osteoblasts, Time Factors, Tissue Scaffolds, Human Umbilical Vein Endothelial Cells, 8-Bromo Cyclic Adenosine Monophosphate, Animals, Humans, Neovascularization, Physiologic, Cell Differentiation, Article, Cell Line
Abstract

Small molecule-based regenerative engineering is emerging as a promising strategy for regenerating bone tissue. Small molecule cAMP analogues have been proposed as novel biofactors for bone repair and regeneration and, while promising, the effect that these small molecules have on angiogenesis, a critical requirement for successful bone regeneration, is still unclear. Our previous research demonstrated that the small molecule cAMP analogue 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP) was able to promote initial osteoblast adhesion on a polymeric scaffold via cAMP signalling cascades. Here, we report that 8-Br-cAMP is capable of inducing in vitro cell-based VEGF production for angiogenesis promotion. We first demonstrated that treating osteoblast-like MC3T3-E1 cells with 8-Br-cAMP for 1 day significantly increased VEGF production and secretion. We then demonstrated that 8-Br-cAMP-induced cell-secreted VEGF is biologically active and may promote angiogenesis, as evidenced by increased human umbilical vein endothelial cells (HUVECs) migration and tubule formation. In addition, treatment of MC3T3-E1 cells with 8-Br-cAMP for as short as a single day resulted in enhanced ALP activity as well as matrix mineralization, demonstrating in vitro osteoblastic differentiation. A short-term 8-Br-cAMP treatment also addresses the concern of non-specific cytotoxicity, as our data indicate that a 1-day 8-Br-cAMP treatment scheme supports cellular proliferation of MC3T3-E1 cells as well as HUVECs. While the major concern associated with small molecule drugs is the risk of non-specific cytotoxicity, the short exposure treatment outlined in this paper provides a very promising strategy to mitigate the risk associated with small molecules. Copyright © 2013 John WileySons, Ltd.

Published
2013

49. Injectable nanocomposite analgesic delivery system for musculoskeletal pain management.

Author

Walker, Joseph, Khanal, Manakamana, Gohil, Shalini V., Kuyinu, Emmanuel, Kan, Ho-Man, Nair, Lakshmi S., Laurencin, Cato T., Lo, Kevin W.-H., Knight, Brittany E., and Baumbauer, Kyle M.

Subjects
NANOCOMPOSITE materials, MUSCULOSKELETAL system, TOTAL knee replacement, TOTAL hip replacement, ANESTHETICS
Abstract

Musculoskeletal pain is a major health issue which results from surgical procedures (i.e. total knee and/or hip replacements and rotator cuff repairs), as well as from non-surgical conditions (i.e. sympathetically-mediated pain syndrome and occipital neuralgia). Local anesthetics, opioids or corticosteroids are currently used for the pain management of musculoskeletal conditions. Even though local anesthetics are highly preferred, the need for multiple administration presents significant disadvantages. Development of unique delivery systems that can deliver local anesthetics at the injection site for prolonged time could significantly enhance the therapeutic efficacy and patient comfort. The goal of the present study is to evaluate the efficacy of an injectable local anesthetic nanocomposite carrier to provide sustained analgesic effect. The nanocomposite carrier was developed by encapsulating ropivacaine, a local anesthetic, in lipid nanocapsules (LNC-Rop), and incorporating the nanocapsules in enzymatically crosslinked glycol chitosan (0.3GC) hydrogels. Cryo Scanning Electron Microscopic (Cryo SEM) images showed the ability to distribute the LNCs within the hydrogel without adversely affecting their morphology. The study demonstrated the feasibility to achieve sustained release of lipophilic molecules from the nanocomposite carrier in vitro and in vivo . A rat chronic constriction injury (CCI) pain model was used to evaluate the efficacy of the nanocomposite carrier using thermal paw withdrawal latency (TWL). The nanocomposite carriers loaded with ropivacaine and dexamethasone showed significant improvement in pain response compared to the control groups for at least 7 days. The study demonstrated the clinical potential of these nanocomposite carriers for post-operative and neuropathic pain. Statement of Significance Acute or chronic pain associated with musculoskeletal conditions is considered a major health issue, with healthcare costs totaling several billion dollars. The opioid crisis presents a pressing clinical need to develop alternative and effective approaches to treat musculoskeletal pain. The goal of this study was to develop a long-acting injectable anesthetic formulation which can sustain a local anesthetic effect for a prolonged time. This in turn could increase the quality of life and rehabilitation outcome of patients, and decrease opioid consumption. The developed injectable nanocomposite demonstrated the feasibility to achieve prolonged pain relief in a rat chronic constriction injury (CCI) model. [ABSTRACT FROM AUTHOR]

Published
2018
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