Molecular Biology of Flexor Tendon Healing in Relation to Reduction of Tendon Adhesions

Legrand, Anaïs; Kaufman, Yoav; Long, Chao; Fox, Paige M.

doi:10.1016/j.jhsa.2017.06.013

Cited by 50 publications

(49 citation statements)

References 36 publications

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“…The collagen membrane alone also may act as a mechanical barrier to scar tissue formation, similar to membranes utilized in the prevention of tendon adhesions, thereby further limiting our ability to detect a difference between the two treatment arms. 28 Another consideration is that the placement of the collagen membrane slows the overall production of collagen in the joint. As the membrane degrades it releases the collagen, resulting decreased collagen and ECM protein production by fibroblasts and myofibroblasts.…”

Section: Histopathology Datamentioning

confidence: 99%

Reduction of arthrofibrosis utilizing a collagen membrane drug‐eluting scaffold with celecoxib and subcutaneous injections with ketotifen

Limberg

Tibbo

Salib

et al. 2020

Journal Orthopaedic Research

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The dense formation of abnormal scar tissue after total knee arthroplasty results in arthrofibrosis, an unfortunate sequela of inflammation. The purpose of this study was to use a validated rabbit model to assess the effects on surgically-induced knee joint contractures of two combined pharmacological interventions: celecoxib (CXB) loaded on an implanted collagen membrane, and subcutaneously (SQ) injected ketotifen. Thirty rabbits were randomly divided into five groups. The first group received no intervention after the index surgery. The remaining four groups underwent intra-articular implantation of collagen membranes loaded with or without CXB at the time of the index surgery; two of which were also treated with SQ ketotifen. Biomechanical joint contracture data were collected at 8, 10, 16, and 24 weeks. At the time of necropsy (24 weeks), posterior capsule tissue was collected for messenger RNA and histopathologic analyses. At 24 weeks, there was a statistically significant increase in passive extension among rabbits in all groups treated with CXB and/or ketotifen compared to those in the contracture control group. There was a statistically significant decrease in COL3A1, COL6A1, and ACTA2 gene expression in the treatment groups compared to the contracture control group (P < .001). Histopathologic data also demonstrated a trend towards decreased fibrous tissue density in the CXB membrane group compared to the vehicle membrane group. The present data suggest that intra-articular placement of a treated collagen membrane blunts the severity of contracture development in a rabbit model of arthrofibrosis, and that ketotifen and CXB may independently contribute to the prevention of arthrofibrosis. Statement of clinical significance: Current literature has demonstrated that arthrofibrosis may affect up to 5% of primary total knee arthroplasty patients. For that reason, novel pharmacologic prophylaxis and treatment modalities are critical to

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Section: Histopathology Datamentioning

confidence: 99%

Reduction of arthrofibrosis utilizing a collagen membrane drug‐eluting scaffold with celecoxib and subcutaneous injections with ketotifen

Limberg

Tibbo

Salib

et al. 2020

Journal Orthopaedic Research

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show abstract

“…Even after successful repair and rehabilitation, about one‐third of patients experience peritendinous adhesions resulting in decreased range of motion (ROM) and diminished functional outcomes of the affected joint . Consequently, there is still a large unmet clinical need to minimize postoperative peritendinous adhesions, with novel biological antiadhesive agents representing a potentially viable solution for this clinical problem …”

Section: Introductionmentioning

confidence: 99%

“…Peritendinous adhesions are largely associated with the extrinsic pathway, where recruitment of extrinsic fibroblasts from peritendinous structures form scar tissue that fail to resolve. Previous antiadhesive strategies include pharmacological anti‐inflammatory agents, physical barriers blocking extrinsic cell recruitment, and inhibition of certain biological mediators associated with scar formation …”

Section: Introductionmentioning

confidence: 99%

“…antiadhesion, cartilage matrix, peritendinous adhesion | E137 PARK et Al physical barriers blocking extrinsic cell recruitment, and inhibition of certain biological mediators associated with scar formation. 4,5 Among available strategies, physical barriers theoretically offer the most effective blockage of extrinsic fibroblast recruitment. Several physical barriers have been developed and are available for clinic use, including materials consisting of poly(L-lactide), hyaluronic acid, hydroxyapatite, and carboxymethyl chitosan.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 Consequently, there is still a large unmet clinical need to minimize postoperative peritendinous adhesions, with novel biological antiadhesive agents representing a potentially viable solution for this clinical problem. 4 It is well known that tendon injuries heal via intrinsic and extrinsic pathways. Peritendinous adhesions are largely associated with the extrinsic pathway, where recruitment of extrinsic fibroblasts from peritendinous structures form scar tissue that fail to resolve.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cross‐linked cartilage acellular matrix film decreases postsurgical peritendinous adhesions

et al. 2019

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Cartilage extracellular matrix contains antiadhesive and antiangiogenic molecules such as chondromodulin‐1, thrombospondin‐1, and endostatin. We have aimed to develop a cross‐linked cartilage acellular matrix (CAM) barrier for peritendinous adhesion prevention. CAM film was fabricated using decellularized porcine cartilage tissue powder and chemical cross‐linking. Biochemical analysis of the film showed retention of collagen and glycosaminoglycans after the fabrication process. Physical characterization of the film showed denser collagen microstructure, increased water contact angle, and higher tensile strength after cross‐linking. The degradation time in vivo was 14 d after cross‐linking. The film extract and film surface showed similar cell proliferation, while inhibiting cell migration and cell adhesion compared to standard media and culture plate, respectively. Application of the film after repair resulted in similar tendon healing and significantly less peritendinous adhesions in a rabbit Achilles tendon injury model compared to repair only group, demonstrated by histology, ultrasonography, and biomechanical testing. In conclusion, the current study developed a CAM film having biological properties of antiadhesion, together with biomechanical properties and degradation profile suitable for prevention of peritendinous adhesions.

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Injectable pH‐Responsive CI1040 Delayed‐Release Hydrogel for the Treatment of Tendon Adhesion

Wu,

Pang,

et al. 2024

Adv Funct Materials

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Tendon injuries, often leading to debilitating adhesions, pose significant challenges in clinical practice. Conventional treatments have limitations, necessitating novel strategies. Injectable hydrogels, known for their biocompatibility, have shown promise. To enhance their antiadhesive properties, researchers have started incorporating drugs. Existing drug delivery systems often peak in the initial days, falling short during the fibroblast proliferation phase which occurs ≈1 week after injury. In this research, CI1040 is selected as an antiadhesion drug, encapsulated within zeolitic imidazolate framework‐8(ZIF‐8), and incorporated into oxidized hyaluronic acid/N‐carboxyethyl chitosan(OHA/CEC) hydrogel(Gel), resulting in the synthesis of CI1040@ZIF@Gel. This unique pH‐responsive drug release system involves encapsulating CI1040 within ZIF‐8, a substance that degrades under acidic conditions while remaining stable in physiological environments. This system selectively releases the drug during the fibroblast proliferation phase, responding to the localized pH reduction post‐tendon injury. CI1040@ZIF@Gel exerted a 65% inhibition on extracellular signal‐regulated kinase (ERK) phosphorylation, reducing the production of collagen types III (Col III) in the adhesion area by 56%. These results indicate that CI1040@ZIF@Gel can effectively inhibit fibroblast proliferation and adhesion through the interleukin 9 receptor/mitogen‐activated protein kinase/extracellular signal‐regulated kinase(IL9r/MEK/ERK) pathway, while also acting as a physical barrier to prevent the formation of tendon adhesion.

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Molecular Biology of Flexor Tendon Healing in Relation to Reduction of Tendon Adhesions

Cited by 50 publications

References 36 publications

Reduction of arthrofibrosis utilizing a collagen membrane drug‐eluting scaffold with celecoxib and subcutaneous injections with ketotifen

Reduction of arthrofibrosis utilizing a collagen membrane drug‐eluting scaffold with celecoxib and subcutaneous injections with ketotifen

Cross‐linked cartilage acellular matrix film decreases postsurgical peritendinous adhesions

Injectable pH‐Responsive CI1040 Delayed‐Release Hydrogel for the Treatment of Tendon Adhesion

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