Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis

Tellier, Liane E.; Treviño, Elda A; Brimeyer, Alexandra L; Reece, David S; Willett, Nick J.; Guldberg, Robert E.; Temenoff, Johnna S.

doi:10.1039/c8bm00010g

Cited by 33 publications

(21 citation statements)

References 52 publications

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“…Using 1 H NMR analysis, PEGDA was determined to be ~55% functionalized and Hep −N methacrylamide was determined to be 22-28% functionalized [36]. SAX-HPLC analysis was also used to assess Hep and Hep −N disaccharide composition.…”

Section: Resultsmentioning

confidence: 99%

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Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury

Tellier

Krieger

Brimeyer

et al. 2018

Regen. Eng. Transl. Med.

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To examine how the chemotactic agent stromal cell-derived factor-1alpha (SDF-1α) modulates the unique cellular milieu within rotator cuff muscle following tendon injury, we developed an injectable, heparin-based microparticle platform to locally present SDF-1α within the supraspinatus muscle following severe rotator cuff injury. SDF-1α loaded, degradable, N-desulfated heparin-based microparticles were fabricated, injected into a rat model of severe rotator cuff injury, and were retained for up to 7 days at the site. The resultant inflammatory cell and mesenchymal stem cell populations were analyzed compared to uninjured contralateral controls and, after 7 days, the fold-change in anti-inflammatory, M2-like macrophages (CD11b+CD68+CD163+, 4.3X fold-change) and mesenchymal stem cells (CD29+CD44+CD90+, 3.0X, respectively) was significantly greater in muscles treated with SDF-1α loaded microparticles than unloaded microparticles or injury alone. Our results indicate that SDF-1α loaded microparticles may be a novel approach to shift the cellular composition within the supraspinatus muscle and create a more pro-regenerative milieu, which may provide a platform to improve muscle repair following rotator cuff injury in the future.

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Section: Resultsmentioning

confidence: 99%

“…Proton nuclear magnetic resonance ( 1 H NMR) was performed to determine the degree of PEGDA and Hep −N MAm functionalization, whereby each material was dissolved at 10 mg/mL in deuterated H 2 O (Sigma), run on a Bruker Avance III spectrometer at 400 Hz, and analyzed using iNMR software [33,36].…”

Section: Methodsmentioning

confidence: 99%

Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury

Tellier

Krieger

Brimeyer

et al. 2018

Regen. Eng. Transl. Med.

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show abstract

“…It is a multifunctional protein with anti-inflammatory and tissue-protective biopotencies [ 52 ]. It has been shown that intra-articular delivery of TNFAIP6 could reduce cartilage damage in a rat model of OA [ 53 ]. However, in the current study, the expression of TNFAIP6 is increased in both cartilage and synovium tissue during OA.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

Zheng

2020

IJMS

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Arthritis is the leading cause of disability among adults, while osteoarthritis (OA) is the most common form of arthritis that results in cartilage loss. However, accumulating evidence suggests that the protective hyaline cartilage should not be the sole focus of OA treatment. Particularly, synovium also plays essential roles in OA’s initiation and progression and warrants serious consideration when battling against OA. Thus, biomarkers with similar OA-responsive expressions in cartilage and synovium should be the potential targets for OA treatment. On the other hand, molecules with a distinguished response during OA in cartilage and synovium should be ruled out as OA therapeutic(s) to avoid controversial effects in different tissues. Here, to pave the path for developing a new generation of OA therapeutics, two published transcriptome datasets of knee articular cartilage and synovium were analyzed in-depth. Genes with statistically significantly different expression in OA and healthy cartilage were compared with those in the synovium. Thirty-five genes with similar OA-responsive expression in both tissues were identified while recognizing three genes with opposite OA-responsive alteration trends in cartilage and synovium. These genes were clustered based on the currently available knowledge, and the potential impacts of these clusters in OA were explored.

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“…Cartilage damage due to injury or disease may cause loss of joint function. Currently prescribed drugs such as TSG‐6 and NSAIDs can only delay the deterioration and relieve the symptoms, but cannot promote tissue restoration . Cartilage lacks the ability to self‐repair and hence cartilage restoration is an important clinical goal .…”

Section: Hydrogel Scaffold For Regenerative Medicinementioning

confidence: 99%

Hydrogels as Emerging Materials for Translational Biomedicine

Ke-min

Wang

Yong

et al. 2018

Advanced Therapeutics

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Hydrogels have been extensively investigated as biomaterials because of their excellent biocompatibility, and recent developments such as 3D printing and the incorporation of dynamic crosslinks have advanced the field considerably. However, the next step of in vivo translational biomedicine requires an understanding of essential hydrogel properties so that they can be designed to overcome the challenges of the living environment. In this review, the stringent design criteria required for in vivo applications are highlighted and recent advances in the repair of organ tissues (heart, bone, eye, etc.) and the therapeutic delivery of bioactive molecules are described. Commercially available hydrogel systems that can be used for translational biomedicine are also discussed, as is the long and sometimes fraught journey from the laboratory to the clinic.The question then arises whether the next iteration of hydrogels can be designed for long-term applications in an in vivo environment with all its complicating agents and factors, and issues such as biodistribution and immune responses. [27][28][29][30] Hydrogels could be prone to dissociation by high shear forces, or the responsiveness to stimuli could be much less sensitive within the body. [31][32][33][34] In this review, we discuss the design of hydrogels for in vivo applications, including for use clinically and commercially. This is not a comprehensive review of the entire field of translational hydrogels, but concentrates on promising results in animal trials. The reader is referred to several reviews which offer a different perspective and provide more detailed information on injectable hydrogels, regenerative scaffolds, and therapeutic delivery. [2,11,24,[35][36][37][38][39]

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Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis

Cited by 33 publications

References 52 publications

Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury

Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury

Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

Hydrogels as Emerging Materials for Translational Biomedicine

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