Fixation of Hydrogel Constructs for Cartilage Repair in the Equine Model: A Challenging Issue

Mancini, Irina A. D.; Bolaños, Rafael A. Vindas; Brommer, Harold; Castilho, Miguel; Ribeiro, Alexandro; Loon, Johannes P.A.M. van; Mensinga, Anneloes; Rijen, Mattie H.P. van; Malda, Jos; Weeren, P. R. van

doi:10.1089/ten.tec.2017.0200

Cited by 38 publications

(55 citation statements)

References 52 publications

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“…The stiffness of both the zonal- and non-zonal constructs at implantation was comparable in our study, which may explain why the amount of bone loss was also comparable in those groups. A comparable issue with PCL-reinforced constructs has been described by Mancini et al and was partially affiliated to the xenogenic fibrin glue [29]. By using a solid press-fit fixation without glue, we were able to eliminate this variable.…”

Section: Discussionmentioning

confidence: 72%

Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

Bothe

Deubel

Hesse

et al. 2019

IJMS

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Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (µCT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage.

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Section: Discussionmentioning

confidence: 72%

Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

Bothe

Deubel

Hesse

et al. 2019

IJMS

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“…[ 19 ] Similarly, a handheld extrusion printer has been developed to simultaneously deliver mesenchymal stromal cells (MSCs) and gelatin-methacryloyl (GelMA) hydrogels into chondral defects in a single-session surgery. [ 17 ] Although promising, both studies demonstrated that the integration of the printed constructs to the native host tissue remained a significant issue, [ 20 ] and in general, the in vivo stability and integration of tissue engineered constructs remains a major challenge in the field of cartilage regeneration. [20–22] Importantly, while stable axial integration can be achieved for treatment strategies targeting osteochondral defect repair, i.e., through anchoring in the subchondral bone, [ 20 ] to achieve a reliable lateral integration within the chondral region is a particularly daunting task.…”

Section: Introductionmentioning

confidence: 99%

“…[ 17 ] Although promising, both studies demonstrated that the integration of the printed constructs to the native host tissue remained a significant issue, [ 20 ] and in general, the in vivo stability and integration of tissue engineered constructs remains a major challenge in the field of cartilage regeneration. [20–22] Importantly, while stable axial integration can be achieved for treatment strategies targeting osteochondral defect repair, i.e., through anchoring in the subchondral bone, [ 20 ] to achieve a reliable lateral integration within the chondral region is a particularly daunting task. This type of integration is especially challenging when using hydrogels or bioinks that display optimal cell embedding properties and thus low mechanical properties.…”

Section: Introductionmentioning

confidence: 99%

One‐Step Photoactivation of a Dual‐Functionalized Bioink as Cell Carrier and Cartilage‐Binding Glue for Chondral Regeneration

Lim

Abinzano

Bernal

et al. 2020

Adv Healthcare Materials

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Cartilage defects can result in pain, disability, and osteoarthritis. Hydrogels providing a chondroregeneration-permissive environment are often mechanically weak and display poor lateral integration into the surrounding cartilage. This study develops a visible-light responsive gelatin ink with enhanced interactions with the native tissue, and potential for intraoperative bioprinting. A dual-functionalized tyramine and methacryloyl gelatin (GelMA-Tyr) is synthesized. Photo-crosslinking of both groups is triggered in a single photoexposure by cell-compatible visible light in presence of tris(2,2'-bipyridyl)dichlororuthenium(II) and sodium persulfate as initiators. Neo-cartilage formation from embedded chondroprogenitor cells is demonstrated in vitro, and the hydrogel is successfully applied as bioink for extrusion-printing. Visible light in situ crosslinking in cartilage defects results in no damage to the surrounding tissue, in contrast to the native chondrocyte death caused by UV light (365–400 nm range), commonly used in biofabrication. Tyramine-binding to proteins in native cartilage leads to a 15-fold increment in the adhesive strength of the bioglue compared to pristine GelMA. Enhanced adhesion is observed also when the ink is extruded as printable filaments into the defect. Visible-light reactive GelMA-Tyr bioinks can act as orthobiologic carriers for in situ cartilage repair, providing a permissive environment for chondrogenesis, and establishing safe lateral integration into chondral defects.

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“…Absence of an adhesive like fibrin glue allowed us to avoid any biocompatibility issues except for those from the construct itself. This may be especially important due to the fact that fibrin glue has shown to produce negative effects such as inferior tissue quality, lower defect filling, and fibrocartilage formation [ 14 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…PCL-reinforcement has also shown promising results for chondral and osteochondral regeneration in vivo [ 12 , 13 ]. However, to date, in vivo studies with PCL-reinforced constructs in large animal models have been limited due to an insufficient fixation within the cartilage defect [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model

Lotz

Bothe

Deubel

et al. 2021

International Journal of Biomaterials

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Reinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of in vivo models for testing the outcome of tissue engineering approaches is implant fixation. The high mechanical stress within the knee joint, as well as the concave and convex cartilage surfaces, makes fixation of reinforced hydrogel challenging. Methods. Different fixation methods for full-thickness chondral defects in minipigs such as fibrin glue, BioGlue®, covering, and direct suturing of nonenforced and enforced constructs were compared. Because of insufficient fixation in chondral defects, superficial osteochondral defects in the femoral trochlea, as well as the femoral condyle, were examined using press-fit fixation. Two different hydrogels (starPEG and PAGE) were compared by 3D-micro-CT (μCT) analysis as well as histological analysis. Results. Our results showed fixation of below 50% for all methods in chondral defects. A superficial osteochondral defect of 1 mm depth was necessary for long-term fixation of a polycaprolactone (PCL)-reinforced hydrogel construct. Press-fit fixation seems to be adapted for a reliable fixation of 95% without confounding effects of glue or suture material. Despite the good integration of our constructs, especially in the starPEG group, visible bone lysis was detected in micro-CT analysis. There was no significant difference between the two hydrogels (starPEG and PAGE) and empty control defects regarding regeneration tissue and cell integration. However, in the starPEG group, more cell-containing hydrogel fragments were found within the defect area. Conclusion. Press-fit fixation in a superficial osteochondral defect in the medial trochlear groove of adult minipigs is a promising fixation method for reinforced hydrogels. To avoid bone lysis, future approaches should focus on multilayered constructs recreating the zonal cartilage as well as the calcified cartilage and the subchondral bone plate.

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Fixation of Hydrogel Constructs for Cartilage Repair in the Equine Model: A Challenging Issue

Cited by 38 publications

References 52 publications

Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

One‐Step Photoactivation of a Dual‐Functionalized Bioink as Cell Carrier and Cartilage‐Binding Glue for Chondral Regeneration

Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model

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