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Article ; Online: Arthroscopic Excision of Pigmented Villonodular Synovitis of the Trochanteric Bursa.

Garrasi, Antonio / Dodge, George R / Kelly, John D

2023 Volume 46, Issue 6, Page(s) e381–e383

Abstract: Trochanteric bursitis is a common disorder affecting middle-aged adults and usually presents with lateral-based hip pain and swelling. It usually responds to conservative measures, including adductor stretching, abductor strengthening, and select ... ...

Abstract	Trochanteric bursitis is a common disorder affecting middle-aged adults and usually presents with lateral-based hip pain and swelling. It usually responds to conservative measures, including adductor stretching, abductor strengthening, and select injections of corticosteroid or platelet-rich plasma. For refractory cases, excision, open or arthroscopic, is usually recommended. We observed a 55-year-old woman who had lateral hip pain and longstanding swelling consistent with refractory trochanteric bursitis. Her persistent symptoms, coupled with atypical findings on imaging, prompted an arthroscopic evaluation. Arthroscopic examination of the peritrochanteric space revealed a fulminant bursal inflammation that pierced through the iliotibial band. The bursal inflammation was excised arthroscopically and biopsy of the tissue revealed a diagnosis of pigmented villonodular synovitis (PVNS). The patient had an uneventful recovery and had a full resolution of symptoms with no recurrence noted at 3-year follow-up. This is the first reported case of arthroscopic excision of PVNS of the trochanteric bursa. Given that it may mimic trochanteric bursitis, it is important for clinicians to be aware of the possibility of this progressive condition for appropriate clinical intervention. [
MeSH term(s)	Humans ; Adult ; Middle Aged ; Female ; Synovitis, Pigmented Villonodular/diagnosis ; Synovitis, Pigmented Villonodular/surgery ; Pain ; Arthralgia ; Bursitis/surgery ; Inflammation
Language	English
Publishing date	2023-05-02
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	424447-3
ISSN	1938-2367 ; 0147-7447
ISSN (online)	1938-2367
ISSN	0147-7447
DOI	10.3928/01477447-20230426-02
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Article ; Online: Self-Assembly Culture Model for Engineering Musculoskeletal Tissues.

DePhillipo, Nicholas N / Martinez, Jerahme / Dodge, George R

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2598, Page(s) 313–323

Abstract: The goal of a self-assembly tissue engineering is to create functional tissue following a natural cell-driven process that mirrors natural development. This approach to tissue engineering has tremendous potential for the development of reparative ... ...

Abstract	The goal of a self-assembly tissue engineering is to create functional tissue following a natural cell-driven process that mirrors natural development. This approach to tissue engineering has tremendous potential for the development of reparative strategies to treat musculoskeletal injuries and diseases, especially for articular cartilage which has poor regenerative capacity. Additionally, many bioengineering and culture methods fail to maintain the chondrocyte phenotype and contain the correct matrix composition in the long term. Existing cartilage-engineering approaches have been developed, but many approaches involve complicated culture techniques and require foreign substances and biomaterials as scaffolds. While these scaffold-based approaches have numerous advantages, such as an instant or rapid creation of biomechanical properties, they frequently result in dedifferentiation of cells in part, due to the adherence to foreign scaffold materials. In this chapter, we describe a novel approach of developing a scaffold-less cartilage-like biomaterial, using the simple principle that cells at high density bear a capacity to coalesce when they cannot attach to any culture substrate. We refer to the biomaterial formed as a cartilage tissue equivalent or CTA and have published to describe their characteristics and utility in high-throughput drug screening. The method is described to generate reproducible cartilage analogs using a specialized high-density suspension culture technique using a hydrogel poly-2-hydroxyethyl methacrylate (polyHEMA) coating of a culture dish. We have demonstrated that this approach can rapidly form biomass of chondrocytes that over time becomes very synthetically active producing a cartilage-like extracellular matrix that closely mimics the biochemical and biomechanical characteristics of native articular cartilage. The culture approach can also be used to form CTA from other than articular cartilage-derived chondrocytes as well as mesenchymal stem cells (MSCs) (while differentiating MSCs into chondrocytes). Some of the advantages are phenotype stability, reproducible CTA size, and biomechanical and biochemical characteristics similar to natural cartilage.
MeSH term(s)	Tissue Engineering/methods ; Chondrocytes ; Cartilage, Articular ; Mesenchymal Stem Cells ; Biocompatible Materials/pharmacology ; Tissue Scaffolds/chemistry ; Chondrogenesis
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2022-11-10
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2839-3_22
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Article ; Online: Evaluation of tendon and ligament microstructure and mechanical properties in a canine model of mucopolysaccharidosis I.

Lau, Yian Khai / Iyer, Keerthana / Shetye, Snehal / Friday, Chet S / Dodge, George R / Hast, Michael W / Casal, Margret L / Gawri, Rahul / Smith, Lachlan J

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2024

Abstract: Mucopolysaccharidosis (MPS) I is a lysosomal storage disorder characterized by deficient alpha-l-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans (GAGs) in cells and tissues. Synovial joint disease is prevalent and ... ...

Abstract	Mucopolysaccharidosis (MPS) I is a lysosomal storage disorder characterized by deficient alpha-l-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans (GAGs) in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a strong clinical need for improved treatment approaches that specifically target joint tissues; however, their development is hampered by poor understanding of underlying disease pathophysiology, including how pathological changes to component tissues contribute to overall joint dysfunction. Ligaments and tendons, in particular, have received very little attention, despite the critical roles of these tissues in joint stability and biomechanical function. The goal of this study was to leverage the naturally canine model to undertake functional and structural assessments of the anterior (cranial) cruciate ligament (CCL) and Achilles tendon in MPS I. Tissues were obtained postmortem from 12-month-old MPS I and control dogs and tested to failure in uniaxial tension. Both CCLs and Achilles tendons from MPS I animals exhibited significantly lower stiffness and failure properties compared to those from healthy controls. Histological examination revealed multiple pathological abnormalities, including collagen fiber disorganization, increased cellularity and vascularity, and elevated GAG content in both tissues. Clinically, animals exhibited mobility deficits, including abnormal gait, which was associated with hyperextensibility of the stifle and hock joints. These findings demonstrate that pathological changes to both ligaments and tendons contribute to abnormal joint function in MPS I, and suggest that effective clinical management of joint disease in patients should incorporate treatments targeting these tissues.
Language	English
Publishing date	2024-02-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.25813
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Article ; Online: Recombinant fibroblast growth factor-18 (sprifermin) enhances microfracture-induced cartilage healing.

Hendesi, Honey / Stewart, Suzanne / Gibison, Michelle L / Guehring, Hans / Richardson, Dean W / Dodge, George R

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2021 Volume 40, Issue 3, Page(s) 553–564

Abstract: Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of ...

Abstract	Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated animals functional and structural outcomes over 24 weeks. For primary outcome measures, we performed histological evaluations and gene expression analysis of aggrecan, collagen types I and II, and cartilage oligomeric matrix protein in three regions of interest. As secondary outcome measures, we examined animals' lameness, performed arthroscopic, radiographic, and computed tomography (CT) scan imaging and gross morphology assessment. We detected the highest treatment benefit following 100 μg sprifermin treatment. The overall histological assessment showed an improvement in the kissing region, and the expression of constitutive genes showed a concentration-dependent enhancement, especially in the peri-lesion area. We detected a significant improvement in lameness scores, arthroscopic evaluations, radiography, and CT scans following sprifermin treatment when results from three dose-treatment groups were combined. Our results demonstrated, for the first time, an enhancement on microfracture outcomes following sprifermin treatment suggesting a cartilage regenerative role and a potential benefit of sprifermin treatment in early cartilage injuries.
MeSH term(s)	Animals ; Cartilage, Articular/pathology ; Fibroblast Growth Factors/metabolism ; Fibroblast Growth Factors/pharmacology ; Fibroblast Growth Factors/therapeutic use ; Fractures, Stress/drug therapy ; Horses ; Lameness, Animal/drug therapy ; Lameness, Animal/metabolism ; Lameness, Animal/pathology
Chemical Substances	fibroblast growth factor 18 ; Fibroblast Growth Factors (62031-54-3)
Language	English
Publishing date	2021-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.25063
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Article: Stretch-responsive adhesive microcapsules for strain-regulated antibiotic release from fabric wound dressings

Jo, Yun Kee / Heo, Su-Jin / Peredo, Ana P. / Mauck, Robert L. / Dodge, George R. / Lee, Daeyeon

Biomaterials science. 2021 July 27, v. 9, no. 15

2021

Abstract: Bacterial infection of a wound is a major complication that can significantly delay proper healing and even necessitate surgical debridement. Conventional non-woven fabric dressings, including gauzes, bandages and cotton wools, often fail in treating ... ...

Abstract	Bacterial infection of a wound is a major complication that can significantly delay proper healing and even necessitate surgical debridement. Conventional non-woven fabric dressings, including gauzes, bandages and cotton wools, often fail in treating wound infections in a timely manner due to their passive release mechanism of antibiotics. Here, we propose adhesive mechanically-activated microcapsules (MAMCs) capable of strongly adhering to a fibrous matrix to achieve a self-regulated release of antibiotics upon uniaxial stretching of non-woven fabric dressings. To achieve this, a uniform population of polydopamine (PDA)-coated MAMCs (PDA-MAMCs) are prepared using a microfluidics technique and subsequent oxidative dopamine polymerization. The PDA-MAMC allows for robust mechano-activation within the fibrous network through high retention and effective transmission of mechanical force under stretching. By validating the potential of a PDA-MAMCs-laden gauze to release antibiotics in a tensile strain-dependent manner, we demonstrate that PDA-MAMCs can be successfully incorporated into a woven material and create a smart wound dressing for control of bacterial infections. This new mechano-activatable delivery approach will open up a new avenue for a stretch-triggered, on-demand release of therapeutic cargos in skin-mountable or wearable biomedical devices.
Keywords	antibiotics ; bacterial infections ; biocompatible materials ; cotton ; debridement ; dopamine ; fabrics ; forces ; microfluidic technology ; polymerization
Language	English
Dates of publication	2021-0727
Size	p. 5136-5143.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d1bm00628b
Database	NAL-Catalogue (AGRICOLA)

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Article: Mechano-activated biomolecule release in regenerating load-bearing tissue microenvironments

Peredo, Ana P / Jo, Yun Kee / Duan, Gang / Dodge, George R / Lee, Daeyeon / Mauck, Robert L

Biomaterials. 2021 Jan., v. 265

2021

Abstract: Although mechanical loads are integral for musculoskeletal tissue homeostasis, overloading and traumatic events can result in tissue injury. Conventional drug delivery approaches for musculoskeletal tissue repair employ localized drug injections. However, ...

Abstract	Although mechanical loads are integral for musculoskeletal tissue homeostasis, overloading and traumatic events can result in tissue injury. Conventional drug delivery approaches for musculoskeletal tissue repair employ localized drug injections. However, rapid drug clearance and inadequate synchronization of molecule provision with healing progression render these methods ineffective. To overcome this, a programmable mechanoresponsive drug delivery system was developed that utilizes the mechanical environment of the tissue during rehabilitation (for example, during cartilage repair) to trigger biomolecule provision. For this, a suite of mechanically-activated microcapsules (MAMCs) with different rupture profiles was generated in a single fabrication batch via osmotic annealing of double emulsions. MAMC physical dimensions were found to dictate mechano-activation in 2D and 3D environments and their stability in vitro and in vivo, demonstrating the tunability of this system. In models of cartilage regeneration, MAMCs did not interfere with tissue growth and activated depending on the mechanical properties of the regenerating tissue. Finally, biologically active anti-inflammatory agents were encapsulated and released from MAMCs, which counteracted degradative cues and prevented the loss of matrix in living tissue environments. This unique technology has tremendous potential for implementation across a wide array of musculoskeletal conditions for enhanced repair of load-bearing tissues.
Keywords	biocompatible materials ; cartilage ; drug delivery systems ; homeostasis ; musculoskeletal system ; tissue repair
Language	English
Dates of publication	2021-01
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2020.120255
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Article ; Online: Preclinical Use of FGF-18 Augmentation for Improving Cartilage Healing Following Surgical Repair: A Systematic Review.

DePhillipo, Nicholas N / Hendesi, Honey / Aman, Zachary S / Lind, Dane R G / Smith, Joseph / Dodge, George R

Cartilage

2022 Volume 14, Issue 1, Page(s) 59–66

Abstract: Objective: To evaluate the efficacy of fibroblast growth factor-18 (FGF-18) augmentation for improving articular cartilage healing following surgical repair in preclinical (: Design: A systematic review was performed evaluating the efficacy of FGF-18 ...

Abstract	Objective: To evaluate the efficacy of fibroblast growth factor-18 (FGF-18) augmentation for improving articular cartilage healing following surgical repair in preclinical ( Design: A systematic review was performed evaluating the efficacy of FGF-18 augmentation with cartilage surgery compared with cartilage surgery without FGF-18 augmentation in living animal models. Eligible intervention groups were FGF-18 treatment in conjunction with orthopedic procedures, including microfracture, osteochondral auto/allograft transplantation, and cellular-based repair. Outcome variables were: International Cartilage Repair Society (ICRS) score, modified O'Driscoll histology score, tissue infill score, qualitative histology, and adverse events. Descriptive statistics were recorded and summarized for each included study. Results: In total, 493 studies were identified and 4 studies were included in the final analysis. All studies were randomized controlled trials evaluating Conclusion: This systematic review provides evidence that rhFGF-18 significantly improves cartilage healing at 6 months postoperatively following microfracture or osteochondral defect repair in preclinical randomized controlled trials.
MeSH term(s)	Animals ; Humans ; Sheep ; Horses ; Fractures, Stress ; Cartilage, Articular/surgery ; Cartilage, Articular/pathology ; Fibroblast Growth Factors/pharmacology ; Fibroblast Growth Factors/therapeutic use ; Collagen
Chemical Substances	fibroblast growth factor 18 ; Fibroblast Growth Factors (62031-54-3) ; Collagen (9007-34-5)
Language	English
Publishing date	2022-12-21
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2515870-3
ISSN	1947-6043 ; 1947-6035
ISSN (online)	1947-6043
ISSN	1947-6035
DOI	10.1177/19476035221142010
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Article ; Online: Proteomics identifies novel biomarkers of synovial joint disease in a canine model of mucopolysaccharidosis I.

Zhang, Chenghao / Gawri, Rahul / Lau, Yian Khai / Spruce, Lynn A / Fazelinia, Hossein / Jiang, Zhirui / Jo, Stephanie Y / Scanzello, Carla R / Mai, Wilfried / Dodge, George R / Casal, Margret L / Smith, Lachlan J

Molecular genetics and metabolism

2023 Volume 138, Issue 2, Page(s) 107371

Abstract: Mucopolysaccharidosis I is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans in cells and tissues. Synovial joint disease is prevalent and significantly reduces ... ...

Abstract	Mucopolysaccharidosis I is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a critical need for improved understanding of joint disease pathophysiology in MPS I, including specific biomarkers to predict and monitor joint disease progression, and response to treatment. The objective of this study was to leverage the naturally-occurring MPS I canine model and undertake an unbiased proteomic screen to identify systemic biomarkers predictive of local joint disease in MPS I. Synovial fluid and serum samples were collected from MPS I and healthy dogs at 12 months-of-age, and protein abundance characterized using liquid chromatography tandem mass spectrometry. Stifle joints were evaluated postmortem using magnetic resonance imaging (MRI) and histology. Proteomics identified 40 proteins for which abundance was significantly correlated between serum and synovial fluid, including markers of inflammatory joint disease and lysosomal dysfunction. Elevated expression of three biomarker candidates, matrix metalloproteinase 19, inter-alpha-trypsin inhibitor heavy-chain 3 and alpha-1-microglobulin, was confirmed in MPS I cartilage, and serum abundance of these molecules was found to correlate with MRI and histological degenerative grades. The candidate biomarkers identified have the potential to improve patient care by facilitating minimally-invasive, specific assessment of joint disease progression and response to therapeutic intervention.
MeSH term(s)	Dogs ; Animals ; Mucopolysaccharidosis I/pathology ; Proteomics ; Quality of Life ; Joint Diseases/metabolism ; Synovial Fluid/metabolism ; Biomarkers/metabolism ; Disease Progression
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1418518-0
ISSN	1096-7206 ; 1096-7192
ISSN (online)	1096-7206
ISSN	1096-7192
DOI	10.1016/j.ymgme.2023.107371
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Article ; Online: Mechano-activated biomolecule release in regenerating load-bearing tissue microenvironments.

Peredo, Ana P / Jo, Yun Kee / Duan, Gang / Dodge, George R / Lee, Daeyeon / Mauck, Robert L

Biomaterials

2020 Volume 265, Page(s) 120255

Abstract	Although mechanical loads are integral for musculoskeletal tissue homeostasis, overloading and traumatic events can result in tissue injury. Conventional drug delivery approaches for musculoskeletal tissue repair employ localized drug injections. However, rapid drug clearance and inadequate synchronization of molecule provision with healing progression render these methods ineffective. To overcome this, a programmable mechanoresponsive drug delivery system was developed that utilizes the mechanical environment of the tissue during rehabilitation (for example, during cartilage repair) to trigger biomolecule provision. For this, a suite of mechanically-activated microcapsules (MAMCs) with different rupture profiles was generated in a single fabrication batch via osmotic annealing of double emulsions. MAMC physical dimensions were found to dictate mechano-activation in 2D and 3D environments and their stability in vitro and in vivo, demonstrating the tunability of this system. In models of cartilage regeneration, MAMCs did not interfere with tissue growth and activated depending on the mechanical properties of the regenerating tissue. Finally, biologically active anti-inflammatory agents were encapsulated and released from MAMCs, which counteracted degradative cues and prevented the loss of matrix in living tissue environments. This unique technology has tremendous potential for implementation across a wide array of musculoskeletal conditions for enhanced repair of load-bearing tissues.
MeSH term(s)	Cartilage ; Regeneration ; Weight-Bearing
Language	English
Publishing date	2020-10-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2020.120255
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Article ; Online: Stretch-responsive adhesive microcapsules for strain-regulated antibiotic release from fabric wound dressings.

Jo, Yun Kee / Heo, Su-Jin / Peredo, Ana P / Mauck, Robert L / Dodge, George R / Lee, Daeyeon

Biomaterials science

2021 Volume 9, Issue 15, Page(s) 5136–5143

Abstract	Bacterial infection of a wound is a major complication that can significantly delay proper healing and even necessitate surgical debridement. Conventional non-woven fabric dressings, including gauzes, bandages and cotton wools, often fail in treating wound infections in a timely manner due to their passive release mechanism of antibiotics. Here, we propose adhesive mechanically-activated microcapsules (MAMCs) capable of strongly adhering to a fibrous matrix to achieve a self-regulated release of antibiotics upon uniaxial stretching of non-woven fabric dressings. To achieve this, a uniform population of polydopamine (PDA)-coated MAMCs (PDA-MAMCs) are prepared using a microfluidics technique and subsequent oxidative dopamine polymerization. The PDA-MAMC allows for robust mechano-activation within the fibrous network through high retention and effective transmission of mechanical force under stretching. By validating the potential of a PDA-MAMCs-laden gauze to release antibiotics in a tensile strain-dependent manner, we demonstrate that PDA-MAMCs can be successfully incorporated into a woven material and create a smart wound dressing for control of bacterial infections. This new mechano-activatable delivery approach will open up a new avenue for a stretch-triggered, on-demand release of therapeutic cargos in skin-mountable or wearable biomedical devices.
MeSH term(s)	Adhesives ; Anti-Bacterial Agents ; Bandages ; Capsules ; Humans ; Wound Infection
Chemical Substances	Adhesives ; Anti-Bacterial Agents ; Capsules
Language	English
Publishing date	2021-07-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d1bm00628b
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