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Article: Five-Year Follow-Up of Distal Tibia Bone and Foot and Ankle Trauma Treated with a 3D-Printed Titanium Cage.

Nwankwo, Eugene C / Chen, Fangyu / Nettles, Dana L / Adams, Samuel B

2019 Volume 2019, Page(s) 7571013

Abstract: Large bone defects from trauma or cancer are difficult to treat. Current treatment options include the use of external fixation with bone transport, bone grafting, or amputation. These modes of therapy continue to pose challenges as they are associated ... ...

Abstract	Large bone defects from trauma or cancer are difficult to treat. Current treatment options include the use of external fixation with bone transport, bone grafting, or amputation. These modes of therapy continue to pose challenges as they are associated with high cost, failure, and complication rates. In this study, we report a successful case of bone defect treatment using personalized 3D-printed implant. This is the longest known follow-up using a 3D-printed custom implant for this specific application. Ultimately, this report adds to existing literature as it demonstrates successful and maintained incorporation of bone into the titanium implant. The use of patient-specific 3D-printed implants adds to the available arsenal to treat complex pathologies of the foot and ankle. Moreover, the technology's flexibility and ease of customization makes it conducive to tailor to specific patient needs.
Language	English
Publishing date	2019-11-26
Publishing country	United States
Document type	Case Reports
ZDB-ID	2684648-2
ISSN	2090-6757 ; 2090-6749
ISSN (online)	2090-6757
ISSN	2090-6749
DOI	10.1155/2019/7571013
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Article: Histological and Inflammatory Cytokine Analysis of Osteochondral Lesions of the Talus After Failed Microfracture: Comparison With Fresh Allograft Controls.

Danilkowicz, Richard M / Allen, Nicholas B / Grimm, Nate / Nettles, Dana L / Nunley, James A / Easley, Mark E / Adams, Samuel B

Orthopaedic journal of sports medicine

2021 Volume 9, Issue 10, Page(s) 23259671211040535

Abstract: Background: The most common first-line treatment of osteochondral lesions of the talus (OLTs) is microfracture. Although many patients do well with this procedure, a number fail and require reoperation. The mechanism of failure of microfracture is ... ...

Abstract	Background: The most common first-line treatment of osteochondral lesions of the talus (OLTs) is microfracture. Although many patients do well with this procedure, a number fail and require reoperation. The mechanism of failure of microfracture is unknown, and to our knowledge there has been no research characterizing failed microfracture regarding histological and inflammatory makeup of these lesions that may contribute to failure. Purpose: To characterize the structural and biochemical makeup of failed microfracture lesions. Study design: Case series; Level of evidence, 4. Methods: Specimens from 8 consecutive patients with symptomatic OLTs after microfracture who later underwent fresh osteochondral allograft transplantation were analyzed. For each patient, the failed microfracture specimen and a portion of the fresh allograft replacement tissue were collected. The allograft served as a control. Histology of the failed microfracture and the allograft replacement was scored using the Osteoarthritis Research Society International (OARSI) system. Surface roughness was also compared. In addition, tissue culture supernatants were analyzed for 16 secreted cytokines and matrix metalloproteinases (MMPs) responsible for inflammation, pain, cartilage damage, and chondrocyte death. Results: The OARSI grade, stage, and total score as well as surface smoothness were significantly worse in the failed microfracture sample, indicating better cartilage and bone morphology for the allografts compared with the failed microfracture lesions. Analyzed cytokines and MMPs were significantly elevated in the microfracture tissue culture supernatants when compared with fresh osteochondral tissue supernatants. Conclusion: These data demonstrate a significantly rougher cartilage surface, cartilage and subchondral bone histology that more closely resembles osteoarthritis, and elevated inflammatory cytokines and MMPs responsible for pain, inflammation, cartilage damage, and chondrocyte death when compared with fresh osteochondral allografts used as controls.
Language	English
Publishing date	2021-10-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2706251-X
ISSN	2325-9671
ISSN	2325-9671
DOI	10.1177/23259671211040535
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Article: The role of metabolomics in osteoarthritis research.

Adams, Samuel B / Setton, Lori A / Nettles, Dana L

The Journal of the American Academy of Orthopaedic Surgeons

2012 Volume 21, Issue 1, Page(s) 63–64

MeSH term(s)	Biomedical Research ; Humans ; Metabolomics ; Osteoarthritis/diagnosis ; Osteoarthritis/metabolism
Language	English
Publishing date	2012-11-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200524-1
ISSN	1940-5480 ; 1067-151X
ISSN (online)	1940-5480
ISSN	1067-151X
DOI	10.5435/JAAOS-21-01-63
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Zs.A 4048: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Time-Dependent Effects on Synovial Fluid Composition During the Acute Phase of Human Intra-articular Ankle Fracture.

Adams, Samuel B / Reilly, Rachel M / Huebner, Janet L / Kraus, Virginia B / Nettles, Dana L

Foot & ankle international

2017 Volume 38, Issue 10, Page(s) 1055–1063

Abstract: Background: The study objective was to examine the effect of time and fracture severity on the undiluted synovial fluid (SF) microenvironment during the acute phase following intra-articular fracture (IAF) of the human ankle.: Methods: Ankle SF from ... ...

Abstract	Background: The study objective was to examine the effect of time and fracture severity on the undiluted synovial fluid (SF) microenvironment during the acute phase following intra-articular fracture (IAF) of the human ankle. Methods: Ankle SF from 54 patients with an acute IAF was analyzed for concentrations of 10 cytokines, 5 matrix metalloproteinases, 2 products of cartilage catabolism, and combined products of heme metabolism. All analytes were correlated with time from fracture and further analyzed for an effect of 3 time subgroups (0-2 days, 3-9 days, and ≥10 days) corresponding to timepoints for clinical ankle fracture interventions. The effect of fracture severity was determined by grouping SF according to the number of radiographic intra-articular fracture lines. Results: Fifteen of 18 analytes were significantly correlated with time. Temporal grouping of SF revealed an initial (0-2 days) spike of pro-inflammatory (IL-12p70, IL-1β, IL-6) and anti-inflammatory (IL-10 and IL-4) cytokines, matrix metalloproteinases (MMP) MMP-9, and sGAG, followed immediately (3-9 days) by products of heme metabolism and an unchallenged surge in mediators and products of cartilage catabolism (MMP-1, MMP-2, MMP-3, MMP-10, and CTX-II). After 10 days, there was a decrease in pro- and anti-inflammatory cytokines but a persistence of mediators of ECM catabolism. There was no clear relationship between the number of fracture lines and SF levels of analytes. Conclusions: This study demonstrated acute temporal fluctuations following ankle IAF resulting in an overall catabolic environment by 10 days post-fracture and supports consideration of an early evacuation of the joint space to reduce the intra-articular inflammatory burden. Clinical Relavence: This study contributes to the understanding of the intra-articular events that potentially contribute to the development of posttraumatic osteoarthritis acutely following IAF in the ankle.
MeSH term(s)	Acute Disease ; Adolescent ; Adult ; Age Factors ; Ankle Fractures/diagnosis ; Ankle Fractures/surgery ; Cohort Studies ; Cytokines/analysis ; Cytokines/metabolism ; Disease Progression ; External Fixators ; Female ; Fracture Fixation, Internal/methods ; Fracture Healing/physiology ; Humans ; Inflammation Mediators/analysis ; Inflammation Mediators/metabolism ; Intra-Articular Fractures/metabolism ; Male ; Matrix Metalloproteinases/analysis ; Matrix Metalloproteinases/metabolism ; Middle Aged ; Osteoarthritis/metabolism ; Osteoarthritis/physiopathology ; Prospective Studies ; Sex Factors ; Statistics, Nonparametric ; Synovial Fluid/metabolism ; Time Factors ; Young Adult
Chemical Substances	Cytokines ; Inflammation Mediators ; Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2017-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1183283-6
ISSN	1944-7876 ; 1071-1007
ISSN (online)	1944-7876
ISSN	1071-1007
DOI	10.1177/1071100717728234
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Article ; Online: Inflammatory cytokines and matrix metalloproteinases in the synovial fluid after intra-articular elbow fracture.

Wahl, Elizabeth P / Lampley, Alexander J / Chen, Angel / Adams, Samuel B / Nettles, Dana L / Richard, Marc J

Journal of shoulder and elbow surgery

2019 Volume 29, Issue 4, Page(s) 736–742

Abstract: Background and hypothesis: Post-traumatic elbow contracture remains a common and challenging complication with often unsatisfactory outcomes. Although the etiology is unknown, elevated or abnormal post-fracture synovial fluid cytokine levels may result ... ...

Abstract	Background and hypothesis: Post-traumatic elbow contracture remains a common and challenging complication with often unsatisfactory outcomes. Although the etiology is unknown, elevated or abnormal post-fracture synovial fluid cytokine levels may result in the migration of fibroblasts to the capsule and contribute to capsular pathology. Thus, the purpose of this study was to characterize the cytokine composition in the synovial fluid fracture hematoma of patients with intra-articular elbow fractures. Methods: The elbow synovial fluid fracture hematoma of 11 patients with intra-articular elbow fractures was analyzed for CTXII (C-terminal telopeptides of type II collagen [a cartilage breakdown product]) as well as 15 cytokines and matrix metalloproteinases (MMPs) including interferon γ, interleukin (IL) 1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor α, MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10. The uninjured, contralateral elbow served as a matched control. Mean concentrations of each factor were compared between the fluid from fractured elbows and the fluid from control elbows. Results: The levels of 14 of 15 measured cytokines and MMPs-interferon γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor α, MMP-1, MMP-3, MMP-9, and MMP-10-were significantly higher in the fractured elbows. In addition, post hoc power analysis revealed that 10 of 14 significant differences were detected with greater than 90% power. The mean concentration of CTXII was not significantly different between groups. Conclusions: These results demonstrate a proinflammatory environment after fracture that may be the catalyst to the development of post-traumatic elbow joint contracture. The cytokines with elevated levels were similar, although not identical, to the cytokines with elevated levels in studies of other weight-bearing joints, indicating the elbow responds uniquely to trauma.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Collagen Type II/metabolism ; Cytokines/metabolism ; Elbow Joint/injuries ; Female ; Hematoma/etiology ; Hematoma/metabolism ; Humans ; Inflammation/metabolism ; Intra-Articular Fractures/complications ; Intra-Articular Fractures/metabolism ; Male ; Matrix Metalloproteinases/metabolism ; Middle Aged ; Peptide Fragments/metabolism ; Prospective Studies ; Synovial Fluid/metabolism
Chemical Substances	C-terminal cross-linking telopeptide of type II collagen, human ; Collagen Type II ; Cytokines ; Peptide Fragments ; Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2019-11-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1170782-3
ISSN	1532-6500 ; 1058-2746
ISSN (online)	1532-6500
ISSN	1058-2746
DOI	10.1016/j.jse.2019.09.024
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Zs.A 3973: Show issues

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Article ; Online: Amino Acid Profile of Synovial Fluid Following Intra-articular Ankle Fracture.

Leimer, Elizabeth M / Tanenbaum, Laura M / Nettles, Dana L / Bell, Richard D / Easley, Mark E / Setton, Lori A / Adams, Samuel B

Foot & ankle international

2018 Volume 39, Issue 10, Page(s) 1169–1177

Abstract: Background: Post-traumatic osteoarthritis (PTOA) is a frequent complication in patients with a previous traumatic joint injury, and the pathophysiology is not well understood. The goal of this study was to characterize the biochemical signature of amino ...

Abstract	Background: Post-traumatic osteoarthritis (PTOA) is a frequent complication in patients with a previous traumatic joint injury, and the pathophysiology is not well understood. The goal of this study was to characterize the biochemical signature of amino acids, peptides, and amino acid metabolites in ankle synovial fluid following intra-articular fracture. Methods: Synovial fluid from both the injured and contralateral ankles of 19 patients with an intra-articular ankle fracture was obtained and analyzed via metabolic profiling. Follow-up analysis was performed after 6 months in 7 of these patients. Results: Statistical comparisons between injured and contralateral ankles revealed that 19 of the 66 measured amino acids, peptides, and amino acid metabolites were significantly elevated at time of fracture. Metabolites associated with glutathione metabolism exhibited the most elevated mean-fold changes, indicating a possible role for oxidative stress in fractured ankles. None of the metabolites elevated at baseline were significantly elevated after 6 months, but 6 metabolites had mean-fold changes greater than 2.1 at this time point. Multiple metabolites also exhibited significant correlations ( r > 0.575) with matrix metalloproteinase-1 and -9. Conclusion: These results indicate the presence of amino acid metabolic products in the setting of ankle fracture and suggest that these changes in amino acid metabolism may be chronic and indicate a role for inflammation and collagen degradation in disease progression. Clinical relevance: Changes in amino acid metabolism following intra-articular fracture may contribute to the progression to PTOA. This knowledge may allow for the identification and early treatment of patients at risk of developing PTOA. Level of evidence: Level III, comparative series.
MeSH term(s)	Adult ; Amino Acids/metabolism ; Ankle Fractures/diagnostic imaging ; Ankle Fractures/metabolism ; Female ; Humans ; Intra-Articular Fractures/diagnostic imaging ; Intra-Articular Fractures/metabolism ; Male ; Middle Aged ; Osteoarthritis/diagnostic imaging ; Osteoarthritis/metabolism ; Retrospective Studies ; Synovial Fluid/metabolism
Chemical Substances	Amino Acids
Language	English
Publishing date	2018-08-15
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	1183283-6
ISSN	1944-7876 ; 1071-1007
ISSN (online)	1944-7876
ISSN	1071-1007
DOI	10.1177/1071100718786163
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Article ; Online: Lipid profile of human synovial fluid following intra-articular ankle fracture.

Leimer, Elizabeth M / Pappan, Kirk L / Nettles, Dana L / Bell, Richard D / Easley, Mark E / Olson, Steven A / Setton, Lori A / Adams, Samuel B

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

2017 Volume 35, Issue 3, Page(s) 657–666

Abstract: This study characterizes the metabolic profile of synovial fluid after intra-articular ankle fracture with an emphasis on changes in the lipid profile. Bilateral ankle synovial fluid from 19 patients with unilateral intra-articular ankle fracture was ... ...

Abstract	This study characterizes the metabolic profile of synovial fluid after intra-articular ankle fracture with an emphasis on changes in the lipid profile. Bilateral ankle synovial fluid from 19 patients with unilateral intra-articular ankle fracture was submitted for metabolic profiling. Contralateral ankle synovial fluid from each patient served as a matched control. Seven patients participated in a second bilateral synovial fluid collection after 6 months. Random forest classification, matched pairs t-tests (α < 0.01), repeated measures ANOVA with post-test contrasts (α < 0.01), correlation to cytokines and matrix metalloproteinases, and fracture and injury classification analyses yielded key lipid biomarkers in synovial fluid following intra-articular fracture. Free fatty acids, sphingomyelins, and lysolipids demonstrated significant elevation in fractured ankles at baseline. Fatty acids and sphingomyelins showed a significant decrease 6 months post-surgery. Random forest analysis showed predominantly fatty acids differentiating between groups. Significant correlations included fatty acids, sphingomyelins, and lysolipids with inflammatory cytokines and matrix metalloproteinases. Fracture classification showed increased fatty acids, lysolipids, and inositol metabolites as fracture severity increased. Fatty acid and sn-1 lysolipid elevation could be detrimental to the joint, as these strongly correlated with matrix metalloproteinases and TNF-α. This elevation also suggests involvement of phospholipase A
MeSH term(s)	Adult ; Ankle Fractures/metabolism ; Female ; Humans ; Lipid Metabolism ; Male ; Middle Aged ; Retrospective Studies ; Synovial Fluid/metabolism ; Young Adult
Language	English
Publishing date	2017-03
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.23217
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Zs.A 1879: Show issues

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Article ; Online: Applications of elastin-like polypeptides in tissue engineering.

Nettles, Dana L / Chilkoti, Ashutosh / Setton, Lori A

Advanced drug delivery reviews

2010 Volume 62, Issue 15, Page(s) 1479–1485

Abstract: Elastin-like polypeptides (ELPs) have found utility in tissue engineering applications, not only because they are biocompatible, biodegradable, and non-immunogenic, but also because their amino acid sequence and molecular weight can be precisely ... ...

Abstract	Elastin-like polypeptides (ELPs) have found utility in tissue engineering applications, not only because they are biocompatible, biodegradable, and non-immunogenic, but also because their amino acid sequence and molecular weight can be precisely controlled at the genetic or synthetic level, affording exquisite control over final protein functionality. This review presents a basic overview of ELP properties and modifications that are relevant to tissue engineering, as well as a discussion of the application of ELPs to cartilage, intervertebral disc, vascular graft, liver, ocular, and cell sheet engineering.
MeSH term(s)	Elastin/chemistry ; Humans ; Peptides/chemistry ; Tissue Engineering/methods
Chemical Substances	Peptides ; Elastin (9007-58-3)
Language	English
Publishing date	2010-04-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2010.04.002
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Zs.A 2241: Show issues

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Article ; Online: Early metabolite levels predict long-term matrix accumulation for chondrocytes in elastin-like polypeptide biopolymer scaffolds.

Nettles, Dana L / Chilkoti, Ashutosh / Setton, Lori A

Tissue engineering. Part A

2008 Volume 15, Issue 8, Page(s) 2113–2121

Abstract: The development of cartilage tissue engineering scaffolds could greatly benefit from methods to evaluate the interactions of cells with scaffolds that are rapid, are nondestructive, and can be carried out at early culture times. Motivated by this ... ...

Abstract	The development of cartilage tissue engineering scaffolds could greatly benefit from methods to evaluate the interactions of cells with scaffolds that are rapid, are nondestructive, and can be carried out at early culture times. Motivated by this rationale, the objective of the current study was to evaluate whether the concentration of metabolites in scaffold-cell cultures at early culture times could predict matrix synthesis in the same samples at longer culture times. Metabolite and matrix synthesis were measured for 16 different formulations of cell-laden elastin-like polypeptide hydrogels. Metabolites were measured at days 4 and 7 of culture, while matrix accumulation was evaluated at day 28. Four of the 16 formulations resulted in molar ratios of lactate:glucose near 2, indicating anaerobic metabolism of glucose, which resulted in collagen:glycosaminoglycan accumulation ratios near those of native tissue. Lactate and pyruvate concentrations were found to significantly correlate with both sulfated glycosaminoglycan and hydroxyproline accumulation, with better fits for the latter. Lactate was found to be the strongest predictor of both matrix components, suggesting that measuring this metabolite at very early culture times may be useful for evaluating the status of tissue engineering constructs in a rapid and nondestructive manner.
MeSH term(s)	Animals ; Cell Count ; Chondrocytes/cytology ; Chondrocytes/metabolism ; Cross-Linking Reagents/metabolism ; Culture Media ; Elastin/metabolism ; Extracellular Matrix/metabolism ; Glycosaminoglycans/metabolism ; Hydroxyproline/metabolism ; Lactic Acid/metabolism ; Peptides/metabolism ; Regression Analysis ; Sus scrofa ; Time Factors ; Tissue Scaffolds
Chemical Substances	Cross-Linking Reagents ; Culture Media ; Glycosaminoglycans ; Peptides ; Lactic Acid (33X04XA5AT) ; Elastin (9007-58-3) ; Hydroxyproline (RMB44WO89X)
Language	English
Publishing date	2008-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2420582-5
ISSN	1937-335X ; 1937-3341
ISSN (online)	1937-335X
ISSN	1937-3341
DOI	10.1089/ten.tea.2008.0448
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Zs.A 5500/A: Show issues

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Article ; Online: Inflammatory Microenvironment Persists After Bone Healing in Intra-articular Ankle Fractures.

Adams, Samuel B / Leimer, Elizabeth M / Setton, Lori A / Bell, Richard D / Easley, Mark E / Huebner, Janet L / Stabler, Thomas V / Kraus, Virginia B / Olson, Steven A / Nettles, Dana L

Foot & ankle international

2017 Volume 38, Issue 5, Page(s) 479–484

Abstract: Background: Post-traumatic osteoarthritis (PTOA) is responsible for the majority of cases of ankle arthritis. While acute and end-stage intra-articular inflammation has previously been described, the state of the joint between fracture healing and end- ... ...

Abstract	Background: Post-traumatic osteoarthritis (PTOA) is responsible for the majority of cases of ankle arthritis. While acute and end-stage intra-articular inflammation has previously been described, the state of the joint between fracture healing and end-stage PTOA remains undefined. This study characterized synovial fluid (SF) composition of ankles after bone healing of an intra-articular fracture to identify factors that may contribute to the development of PTOA. Methods: Of an original 21 patients whose SF was characterized acutely following intra-articular ankle fractures, 7 returned for planned hardware (syndesmotic screw) removal after bone healing (approximately 6 months) and consented to a second bilateral SF collection. SF concentrations of 15 cytokines and matrix metalloproteinases (MMPs) and 2 markers each of cartilage catabolism (CTXII and glycosaminoglycan) and hemarthrosis (biliverdin and bilirubin) were compared for previously fractured and contralateral, uninjured ankles from the same patient. Analysis was also performed to determine the effect of the number of fracture lines and involvement of soft tissue on SF composition. Results: Interleukin (IL)-6, IL-8, MMP-1, MMP-2, and MMP-3 were significantly elevated in the SF from healed ankles compared to matched contralateral uninjured ankles at approximately 6 months after fracture. There were no differences in markers of cartilage catabolism or hemarthrosis. Only IL-1α was affected by the number of fracture lines while differences were not detected for other analytes or with respect to the involvment of soft tissue. Conclusions: Sustained intra-articular inflammation, even after complete bone healing, was suggested by elevations of pro-inflammatory cytokines (IL-6 and IL-8). In addition, elevated concentrations of MMPs were also noted and were consistent with a persistent inflammatory environment. This study suggests new evidence of persistent intra-articular inflammation after intra-articular ankle fracture healing and suggests potential mediators for PTOA development. Clinical relevance: This work may be relevant to the clinical diagnosis and treatment of post-traumatic osteoarthritis.
MeSH term(s)	Ankle Fractures/physiopathology ; Ankle Fractures/surgery ; Biomarkers ; Cytokines/chemistry ; Cytokines/metabolism ; Humans ; Inflammation Mediators/metabolism ; Inflammation Mediators/physiology ; Interleukin-6/chemistry ; Interleukin-6/metabolism ; Intra-Articular Fractures/surgery ; Matrix Metalloproteinases/chemistry ; Matrix Metalloproteinases/metabolism ; Osteoarthritis/metabolism ; Osteoarthritis/physiopathology ; Synovial Fluid/chemistry ; Synovial Fluid/metabolism
Chemical Substances	Biomarkers ; Cytokines ; Inflammation Mediators ; Interleukin-6 ; Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2017-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1183283-6
ISSN	1944-7876 ; 1071-1007
ISSN (online)	1944-7876
ISSN	1071-1007
DOI	10.1177/1071100717690427
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