Osteochondral tissue engineering

Martin, Ivan; Miot, Sylvie; Barbero, Andrea; Jakob, Marcel; Wendt, David

doi:10.1016/j.jbiomech.2006.03.008

Cited by 332 publications

(301 citation statements)

References 87 publications

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“…Damage to the articular surface can penetrate to the subchondral bone and such osteochondral defects are often associated with mechanical instability of the joint and warrant surgical intervention in order to prevent osteoarthritic degenerative changes [1]. Even in cases where lesions do not penetrate to the subchondral bone an osteochondral construct may be a more desirable implant as a bone-to-bone interface integrates better than a cartilage-to-cartilage interface [2].…”

Section: Introductionmentioning

confidence: 99%

Engineering osteochondral constructs through spatial regulation of endochondral ossification

et al. 2013

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Chondrogenically primed bone marrow derived mesenchymal stem cells (MSCs) have been shown to become hypertrophic and undergo endochondral ossification when implanted in vivo. Modulating this endochondral phenotype may be an attractive approach to engineering the osseous phase of an osteochondral implant. The objective of this study was to engineer an osteochondral tissue by promoting endochondral ossification in one layer of a bi-layered construct and stable cartilage in the other. The top-half of bi-layered agarose hydrogels were seeded with culture expanded chondrocytes (termed chondral layer) and the bottom half of the bi-layered agarose hydrogels with MSCs (termed osseous layer). Constructs were cultured in a chondrogenic medium for 21 days and thereafter were either maintained in a chondrogenic medium, transferred to a hypertrophic medium, or implanted subcutaneously into nude mice. This structured chondrogenic bi-layered co-culture was found to enhance chondrogenesis in the chondral layer, appearing to help re-establish the chondrogenic phenotype that is lost in chondrocytes during monolayer expansion. Furthermore, the bilayered co-culture appeared to suppress hypertrophy and mineralisation in the osseous layer.The addition of hypertrophic factors to the media was found to induce mineralisation of the osseous layer in vitro. A similar result was observed in vivo where endochondral ossification was restricted to the osseous layer of the construct leading to the development of an osteochondral tissue. This novel approach represents a potential new treatment strategy for the repair of osteochondral defects.

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Section: Introductionmentioning

confidence: 99%

Engineering osteochondral constructs through spatial regulation of endochondral ossification

et al. 2013

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“…Even if a series of therapeutic approaches has been developed to treat osteochondral defects, none of them has proved yet to ensure long-lasting regeneration. Considering the intrinsically different biological, biochemical and biomechanical properties of the articular cartilage / subchondral bone system, several groups have directed their efforts into the generation of osteochondral composite materials and/or engineered tissues, using a rather large variety of approaches [5][6][7][8][9][10]. One of the most promising strategies consists in the generation of heterogenous scaffolds, obtained by the combination of distinct but integrated layers corresponding to the cartilage and bone regions.…”

Section: Introductionmentioning

confidence: 99%

Design of graded biomimetic osteochondral composite scaffolds

et al. 2008

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With the ultimate goal to generate suitable materials for the repair of osteochondral defects, in this work we aimed at developing composite osteochondral scaffolds organized in different integrated layers, with features which are biomimetic for articular cartilage and subchondral bone and can differentially support formation of such tissues.A biologically inspired mineralization process was first developed to nucleate Mg-doped hydroxyapatite crystals on type I collagen fibers during their self assembling. The resulting mineral phase was non-stoichiometric and amorphous, resembling chemico-physical features of newly deposited, natural bone matrix. A graded material was then generated, consisting of (i) a lower layer of the developed biomineralized collagen, corresponding to the subchondral bone, (ii) an upper layer of hyaluronic acid-charged collagen, mimicking the cartilaginous region, and (iii) an intermediate layer of the same nature as the biomineralized collagen, but with a lower extent of mineral, resembling the tidemark. The layers were stacked and freeze-dried, to obtain an integrated, monolithic composite. Culture of the material for 2 weeks after loading with articular chondrocytes yielded cartilaginous tissue formation selectively in the upper layer. Conversely, ectopic implantation in nude mice of the material after loading with bone marrow stromal cells resulted in bone formation which remained confined within the lower layer.In conclusion, we developed a composite material with cues which are biomimetic of an osteochondral tissue and with the capacity to differentially support cartilage and bone tissue generation. The results warrant test of the material as a substitute for the repair of osteochondral lesions in orthotopic animal models. Response to Reviewer #1:1) results and discussion should be separated We would prefer to maintain Results and Discussion combined, in order to avoid possible redundancies and improve readability. 2) figures should be detailed with arrows and information about specific orientations. Details and arrows have been included in the Figures3) collagen type 1 was used for the creation of the construct -in every layer? Usually collagen type 1 does not play a role in articular cartilage. This should be addressed in the discussion. According to the Reviewer's comment, a rationale for the use of type I collagen has been included in the text, as follows: "Type I collagen was selected for the synthesis of the composite layers, including the cartilaginous one, due to (i) its good physico-chemical stability and processability and (ii) high safety and biocompatibility profile, related to the removal of all Reply Letter to Editor and referee's comments telopeptides, which are potentially responsible for immunological reactions." (Section 2.1, Page 2, 1 st paragraph). Indeed, type II collagen is normally extracted porcine derivative, and is still not available either in bulk for processing or for clinical use. Nowadays there are only few papers on experimental studies desc...

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“…By contrast, harvesting of adult autologous articular chondrocytes involves joint biopsy, and the cells tend to dedifferentiate during expansion [35,59]. Approaches currently being studied include growth factor supplementation during cell expansion and culture [60,61], use of additional cell sources (such as nasal, ear and rib cartilage) [62], adipose-derived hMSCs [24] and cell co-culture [27,63]. Several products have utilized autologous cells in a synthetic matrix for focal cartilage repair, such as Bioseed ® C (http://www.biotissue-tec.com/index.php?idcat=122) and Hyalograft ® C (http://www.fidiapharma.com/files/index.cfm?id_rst=104&id_elm=31) [64].…”

Section: Summary and Future Directionsmentioning

confidence: 99%

Engineering custom-designed osteochondral tissue grafts

Grayson

Chao

Marolt

et al. 2008

Trends in Biotechnology

123

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Tissue engineering is expected to help us outlive the failure of our organs by enabling the creation of tissue substitutes capable of fully restoring the original tissue function. Degenerative joint disease, which affects one-fifth of the US population and is the country's leading cause of disability, drives current research of actively growing, functional tissue grafts for joint repair. Toward this goal, living cells are used in conjunction with bio-material scaffolds (serving as instructive templates for tissue development) and bioreactors (providing environmental control and molecular and physical regulatory signals). In this review, we discuss the requirements for engineering customized, anatomically-shaped, stratified grafts for joint repair and the challenges of designing these grafts to provide immediate functionality (load bearing, structural support) and long-term regeneration (maturation, integration, remodeling).

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Osteochondral tissue engineering

Cited by 332 publications

References 87 publications

Engineering osteochondral constructs through spatial regulation of endochondral ossification

Engineering osteochondral constructs through spatial regulation of endochondral ossification

Design of graded biomimetic osteochondral composite scaffolds

Engineering custom-designed osteochondral tissue grafts

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