Chondrocyte-seeded collagen matrices implanted in a chondral defect in a canine model

Nehrer, Stefan; Breinan, Howard A.; Ramappa, Arun J.; Hsu, Hu‐Ping; Minas, Tom; Shortkroff, Sonya; Sledge, C. B.; Yannas, Ioannis V.; Spector, Myron

doi:10.1016/s0142-9612(98)00143-4

Cited by 234 publications

(125 citation statements)

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“…The amount of reparative tissue filling the defects implanted with the cell-seeded scaffolds in the current study (88 i 6' Yn) was considerably greater than the amount of tissue (34 i 7%) found in untreated defects evaluated previously using the same model after a comparable implantation period (Fig. 5) [6,28]. This indicates that the cell-seeded scaffolds remained in the defects for a sufficient amount of time to Compared to repair tissue filling defects after other treatment protocols, the four week in vitro culture of the construct prior to implantation increased the total amount of fill and the percentage of the repair tissue that was hyaline-like, while decreasing the amount of fibrous tissue.…”

Section: Discussioncontrasting

confidence: 47%

“…Implantation of cells alone [6,7,28] does not lead to as significant a disruption of the tidemark, indicating that the scaffold contributes to bony resorption in some way. Possible pathways include a direct bone cell reaction to the scaffold or to degradation products of the scaffold or bone cell regulation by factors released by other cells (i.e., synovial cells or chondrocytes) in response to the scaffold.…”

Section: Discussionmentioning

confidence: 99%

“…The objective was to evaluate the healing of cartilage defects implanted with autologous chondrocyte-seeded type I1 collagen scaffolds that had been cultured in vitro for four wceks prior to implantation. This study employed the canine model previously reported [6,7,28,33]. Prior work with this model has C.R.…”

Section: Introductionmentioning

confidence: 99%

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Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model

Lee

Grodzinsky

Hsu

et al. 2003

Journal Orthopaedic Research

186

110

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Using a previously established canine model for repair of articular cartilage defects, this study evaluated the 15-week healing of chondral defects (i.e., to the tidemark) implanted with an autologous articular chondrocyte-seeded type I1 collagen scaffold that had been cultured in vitro for four weeks prior to implantation. The amount and composition of the reparative tissue were compared to results from our prior studies using the same animal model in which the following groups were analyzed: defects implanted with autologous chondrocyte-seeded collagen scaffolds that had been cultured in vitro for approximately 12 h prior to implantation, defects implanted with autologous chondrocytes alone, and untreated defects. Chondrocytes, isolated from articular cartilage harvested from the left knee joint of six adult canines, were expanded in number in monolayer for three weeks, seeded into porous type I1 collagen scaffolds. cultured for an additional four weeks in vitro and then implanted into chondral defects in the trochlear groove of the right knee joints. The percentages of specific tissue types filling the defects were evaluated histomorphoinetrically and certain mechanical properties of the repair tissue were determined. The reparative tissue filled 88 f 6% (mean * SEM; range 70-100%) of the cross-sectional area of the original defect. with hyaline cartilage accounting for 42 f 10%) (range 7-67'%)) of defect area. These values were greater than thosc reported previously for untreated defects and defects implanted with a type I1 collagen scaffold seeded with autologous chondrocytes within 12 h prior to implantation. Most striking, was the decreased amount of fibrous tissue filling the defects in the current study, 5 & 5%) (range 0-26%) as compared to previous treatments. Despite this improvement, indentation testing of the repair tissue formed in this study revealed that the compressive stiffness of the repair tissue was well below (20-fold lower stiffness) that of native articular cartilage.

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Section: Discussioncontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

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Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model

Lee

Grodzinsky

Hsu

et al. 2003

Journal Orthopaedic Research

186

110

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“…CG matrices were produced as described 29,35 by freeze-drying and subsequent UV irradiation cross-linking of a co-precipitate of collagen type II from porcine cartilage and chondroitin-6-sulfate from shark. The collagen matrix was prepared in sheets, 2 mm in thickness.…”

Section: Gene Delivery Via Bone Marrow Clotsmentioning

confidence: 99%

Gene delivery to cartilage defects using coagulated bone marrow aspirate

et al. 2004

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The long-term goal of the present study is to develop a clinically applicable approach to enhance natural repair mechanisms within cartilage lesions by targeting bone marrow-derived cells for genetic modification. To determine if bone marrow-derived cells infiltrating osteochondral defects could be transduced in situ, we implanted collagen-glycosaminoglycan (CG) matrices preloaded with adenoviral vectors containing various marker genes into lesions surgically generated in rabbit femoral condyles. Analysis of the recovered implants showed transgenic expression up to 21 days; however, a considerable portion was found in the synovial lining, indicating leakage of the vector and/or transduced cells from the matrix. As an alternative medium for gene delivery, we investigated the feasibility of using coagulated bone marrow aspirates. Mixture of an adenoviral suspension with the fluid phase of freshly aspirated bone marrow resulted in uniform dispersion of the vector throughout, and levels of transgenic expression in direct proportion to the density of nucleated cells in the ensuing clot. Furthermore, cultures of mesenchymal progenitor cells, previously transduced ex vivo with recombinant adenovirus, were readily incorporated into the coagulate when mixed with fresh aspirate. These vector-seeded and cell-seeded bone marrow clots were found to maintain their structural integrity following extensive culture and maintained transgenic expression in this manner for several weeks. When used in place of the CG matrix as a gene delivery vehicle in vivo, genetically modified bone marrow clots were able to generate similarly high levels of transgenic expression in osteochondral defects with better containment of the vector within the defect. Our results suggest that coagulates formed from aspirated bone marrow may be useful as a means of gene delivery to cartilage and perhaps other musculoskeletal tissues. Cells within the fluid can be readily modified with an adenoviral vector, and the matrix formed from the clot is completely natural, native to the host and is the fundamental platform on which healing and repair of mesenchymal tissues is based.

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“…This approach allows a more predictable transport of the cells into the defect without the need for suturing. Most of the biomaterials used in these techniques are natural biopolymers such as collagen [7,8,24] or hyaluronan [10,21,27] derived from animals or synthetic materials like polylactides [6].…”

Section: Introductionmentioning

confidence: 99%

Results of Chondrocyte Implantation with a Fibrin-Hyaluronan Matrix: A Preliminary Study

Nehrer

Chiari

Domayer

et al. 2008

Clin Orthop Relat Res

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Fibrin, a homologous polymer, is the natural scaffold of wound healing and therefore a candidate as a carrier for cell transplantation. We explored a novel matrix-based implant cartilage repair composed of both fibrin and hyaluronan in a defined ratio that takes advantage of the biological and mechanical properties of these two elements. The matrix was seeded with autologous chondrocytes expanded in the presence of a proprietary growth factor variant designed to preserve their chondrogenic potential. We prospectively followed eight patients with symptomatic-chronic cartilage defects treated with this carrier. Patients had arthroscopy to harvest autologous chondrocytes then grown in autologous serum. Chondrocytes were cultured in the presence of the FGF variant and then seeded on the fibrin-hyaluronan matrix. About 4 weeks following biopsy, the patients underwent implantation of the constructs by miniarthrotomy. Three of the eight patients had transient effusion. Clinical performance was measured by Lysholm and IKDC scores, MRI, and the need for secondary surgery. The clinical outcome of a 1-year followup demonstrated increase of clinical scores.

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Chondrocyte-seeded collagen matrices implanted in a chondral defect in a canine model

Cited by 234 publications

References 0 publications

Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model

Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model

Gene delivery to cartilage defects using coagulated bone marrow aspirate

Results of Chondrocyte Implantation with a Fibrin-Hyaluronan Matrix: A Preliminary Study

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