Enhancement of Rotator Cuff Healing with Farnesol-Impregnated Gellan Gum/Hyaluronic Acid Hydrogel Membranes in a Rabbit Model

Lin, Yen‐Hung; Lee, Sheng-I; Lin, Feng-Huei; Wu, Guan-Xuan; Wu, Chun-Shien; Kuo, Shyh-Ming

doi:10.3390/pharmaceutics13070944

Cited by 11 publications

(12 citation statements)

References 35 publications

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“…13 During rotator cuff healing after rotator cuff repair, inflammatory cells accumulate and result in fibrotic tissue formation, which impairs tendon healing instead of regenerating the tendon itself. 13,28,34 HA possesses anti-inflammatory properties; thus, it promotes tendon-to-bone healing. 8 Moreover, HA binds and interacts with specific cell-associated receptors, such as CD44.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Combining Hyaluronic Acid and Human Dermal Fibroblasts on Tendon Healing

Rhee,

Jeon,

Han

et al. 2023

Am J Sports Med

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Background: The incidence of rotator cuff tears is rapidly increasing, and operative techniques for rotator cuff repair have been developed. However, the rates of postoperative retear remain high. Purpose/Hypothesis: The purpose was to determine the effects of human dermal fibroblasts (HDFs) with hyaluronic acid (HA) on tendon-to-bone healing in a rabbit model of chronic rotator cuff tear injury. It was hypothesized that HA would enhance HDF proliferation and that a combination of HA and HDFs would produce a synergistic effect on the healing of repaired rotator cuff tendons of rabbits. Study Design: Controlled laboratory study. Methods: For in vitro study, HDFs were plated on a 24-well plate. After 1 day, 2 wells were designated as the test group and treated with 0.75% HA in phenol red–free Dulbecco's modified Eagle medium (DMEM). An other 2 wells served as control groups and were treated with the same volume of phenol red–free DMEM without HA. Each group was duplicated, resulting in a total of 4 wells, with 2 wells in each group for replication purposes. The cells were incubated for 24 hours, followed by 72-hour cultivation. Absorbance ratios at 96 and 24 hours were compared to evaluate cell proliferation. For the in vivo study, a total of 24 rabbits were randomly allocated to groups A, B, and C (n = 8 each). Supraspinatus tendons were detached bilaterally and left for 6 weeks to establish a chronic rotator tear model. Torn tendons were subsequently repaired using the following injections: group A, 0.5 × 106 HDFs with HA; group B, HA only; and group C, saline only. At 12 weeks after repair, biomechanical tests and histological evaluation were performed. Results: In vitro study showed that HDF proliferation significantly increased with HA (HDFs with HA vs HDFs without HA; 3.96 ± 0.09 vs 2.53 ± 0.15; P < .01). In vivo, group A showed significantly higher load-to-failure values than the other groups (53.8 ± 6.9 N/kg for group A, 30.6 ± 6.4 N/kg for group B, and 24.3 ± 7.6 N/kg for group C; P < .001). Histological evaluation confirmed that group A showed higher collagen fiber density and better collagen fiber continuity, tendon-to-bone interface maturation, and nuclear shape than the other groups (all P < .05). Conclusion: This controlled laboratory study verified the potential of the combination of HDFs and HA in enhancing healing in a chronic rotator cuff tear rabbit model. Clinical Relevance: A potential synergistic effect on rotator cuff tendon healing may be expected from a combination of HDFs and HA.

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Section: Discussionmentioning

confidence: 99%

The Effect of Combining Hyaluronic Acid and Human Dermal Fibroblasts on Tendon Healing

Rhee,

Jeon,

Han

et al. 2023

Am J Sports Med

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“…The membranes could swell rapidly and adhere to the tear site, acting as a barrier and farnesol source during the repair period. Results indicated that farnesol enhanced collagen production and the hydrogel membranes was promising in the repair of rotator cuff injuries ( Lin et al, 2021 ).…”

Section: The Functions Of Hydrogel Used In Rotator Cuff Repairmentioning

confidence: 99%

“…(B) In vivo application and evaluation of Cur&Mg-QCS/PF hydrogels. (Reprinted from ( Lin et al, 2021 ) with permission from Theranostics).…”

Section: The Functions Of Hydrogel Used In Rotator Cuff Repairmentioning

confidence: 99%

Hydrogel Development for Rotator Cuff Repair

Fang

Chen

et al. 2022

Front. Bioeng. Biotechnol.

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Rotator cuff tears (RCTs) are common in shoulder disease and disability. Despite significant advances in surgical repair techniques, 20–70% of patients still have postoperative rotator cuff dysfunction. These functional defects may be related to retear or rotator cuff quality deterioration due to tendon retraction and scar tissue at the repair site. As an effective delivery system, hydrogel scaffolds may improve the healing of RCTs and be a useful treatment for irreparable rotator cuff injuries. Although many studies have tested this hypothesis, most are limited to laboratory animal experiments. This review summarizes differences in hydrogel scaffold construction, active ingredients, and application methods in recent research. Efforts to determine the indications of hydrogel scaffolds (with different constructions and cargos) for various types of RCTs, as well as the effectiveness and reliability of application methods and devices, are also discussed.

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“… 19 Farnesol can modulate connective tissue and ECM synthesis, which is required for wound healing 20 and rotator cuff repair. 21 Cartilage reconstruction is challenging because cartilage has poor intrinsic defect-repairing abilities. Studies have identified that in chondrocytes, phenotypic instability occurs with changes in the cell volume and morphology before considerable cartilage degeneration and loss, which might be essential for indicating the early stages of cartilage loss.…”

Section: Introductionmentioning

confidence: 99%

Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis

Chen¹,

Kuo

et al. 2023

APL Bioengineering

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Articular cartilage may regenerate poorly after injury or during aging. In vitro, farnesol can modulate extracellular matrix synthesis and restore chondrocyte phenotypes by increasing type II collagen (COL II) and glycosaminoglycan (GAG) production. Here, we evaluated farnesol's preventive and reparative effects against osteoarthritis (OA) in vivo. We induced OA in rabbits through resection of the lateral collateral ligament and meniscus. After 2 weeks, the affected limb was treated with 0.5 ml of 0.4 mM farnesol, hyaluronan (HA) nanoparticle-encapsulated 0.8 mM farnesol (Farn/HA), or HA nanoparticles intra-articularly. After 2 and 6 treatment weeks, synovial inflammatory cytokine levels were analyzed. We also removed the entire joint cartilage from lateral femoral condyles for histological investigation. The half-maximum inhibitory concentration of farnesol was 0.5 mM. Farn/HA had relatively low cytotoxicity showing cells remained viable after being treated with 1 mM a concentration Farn/HA. Untreated lateral condyle exhibited extensive wear. By contrast, 0.4 mM farnesol or 0.8 mM Farn/HA led to a relatively transparent and bright appearance. After 2 and 6 treatment weeks, farnesol, particularly 0.8 mM Farn/HA, reduced matrix metalloproteinase 1 and 13 levels considerably. Therefore, 0.8 mM Farn/HA, which enabled slow drug release, demonstrated the highest anti-inflammatory and OA preventive effects. After 6 treatment weeks, farnesol also promoted COL II and GAG synthesis and, thus, aided healing.

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Enhancement of Rotator Cuff Healing with Farnesol-Impregnated Gellan Gum/Hyaluronic Acid Hydrogel Membranes in a Rabbit Model

Cited by 11 publications

References 35 publications

The Effect of Combining Hyaluronic Acid and Human Dermal Fibroblasts on Tendon Healing

The Effect of Combining Hyaluronic Acid and Human Dermal Fibroblasts on Tendon Healing

Hydrogel Development for Rotator Cuff Repair

Synergistic prevention and reparative effects of sesquiterpene farnesol in a rabbit model of surgical resection-induced osteoarthritis

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