A Bioactive Cartilage Graft of IGF1-Transduced Adipose Mesenchymal Stem Cells Embedded in an Alginate/Bovine Cartilage Matrix Tridimensional Scaffold

Moncada‐Saucedo, Nidia K.; Marino-Martínez, Iván Alberto; Lara‐Arias, Jorge; Romero-Díaz, Viktor J; Camacho, Alberto; Valdés-Franco, J. A.; Pérez-Silos, Vanessa; García-Ruiz, Alejandro; Lin, Hang; Tuan, Rocky S.; Ramos‐Payán, Rosalío; Lara-Banda, María; Ortı́z-López, Rocio; Rojas-Martínez, Augusto; Fuentes-Mera, Lizeth

doi:10.1155/2019/9792369

Cited by 6 publications

(14 citation statements)

References 51 publications

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“…To overcome mechanical tissue demands, a strategy used by our group [16] and others has been to incorporate decellularized ECM processed in the form of micronized particles.…”

Section: Discussionmentioning

confidence: 99%

“…In this sense, biofunctionalization with an ECM derived from several tissues and decellularized organs has become more attractive and is used for the regeneration of tissues, such as skeletal muscle [12], blood vessels [13], nerves [14], and cartilage [15,16]. The ECM provides informative signals and a unique composition that mimics the natural tissue environment and leads to proper tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

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A Cellularized Biphasic Implant Based on a Bioactive Silk Fibroin Promotes Integration and Tissue Organization during Osteochondral Defect Repair in a Porcine Model

Pérez-Silos

Moncada‐Saucedo

Peña‐Martínez

et al. 2019

IJMS

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In cartilage tissue engineering, biphasic scaffolds (BSs) have been designed not only to influence the recapitulation of the osteochondral architecture but also to take advantage of the healing ability of bone, promoting the implant’s integration with the surrounding tissue and then bone restoration and cartilage regeneration. This study reports the development and characterization of a BS based on the assembly of a cartilage phase constituted by fibroin biofunctionalyzed with a bovine cartilage matrix, cellularized with differentiated autologous pre-chondrocytes and well attached to a bone phase (decellularized bovine bone) to promote cartilage regeneration in a model of joint damage in pigs. BSs were assembled by fibroin crystallization with methanol, and the mechanical features and histological architectures were evaluated. The scaffolds were cellularized and matured for 12 days, then implanted into an osteochondral defect in a porcine model (n = 4). Three treatments were applied per knee: Group I, monophasic cellular scaffold (single chondral phase); group II (BS), cellularized only in the chondral phase; and in order to study the influence of the cellularization of the bone phase, Group III was cellularized in chondral phases and a bone phase, with autologous osteoblasts being included. After 8 weeks of surgery, the integration and regeneration tissues were analyzed via a histology and immunohistochemistry evaluation. The mechanical assessment showed that the acellular BSs reached a Young’s modulus of 805.01 kPa, similar to native cartilage. In vitro biological studies revealed the chondroinductive ability of the BSs, evidenced by an increase in sulfated glycosaminoglycans and type II collagen, both secreted by the chondrocytes cultured on the scaffold during 28 days. No evidence of adverse or inflammatory reactions was observed in the in vivo trial; however, in Group I, the defects were not reconstructed. In Groups II and III, a good integration of the implant with the surrounding tissue was observed. Defects in group II were fulfilled via hyaline cartilage and normal bone. Group III defects showed fibrous repair tissue. In conclusion, our findings demonstrated the efficacy of a biphasic and bioactive scaffold based on silk fibroin and cellularized only in the chondral phase, which entwined chondroinductive features and a biomechanical capability with an appropriate integration with the surrounding tissue, representing a promising alternative for osteochondral tissue-engineering applications.

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“…To overcome mechanical tissue demands, a strategy used by our group [16] and others has been to incorporate decellularized ECM processed in the form of micronized particles.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Cellularized Biphasic Implant Based on a Bioactive Silk Fibroin Promotes Integration and Tissue Organization during Osteochondral Defect Repair in a Porcine Model

Pérez-Silos

Moncada‐Saucedo

Peña‐Martínez

et al. 2019

IJMS

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“…To isolate Ad-MSCs, a modified version of the isolation protocol described in Moncada-Saucedo et al ( 19 ) was followed ( 20 ). To achieve this, lipoaspirate was centrifuged for 10 min at 1,000 x g in a 4˚C refrigerated centrifuge (5804R; Eppendorf), the aqueous phase was discarded and the adipose tissue was washed with PBS (pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant

et al. 2021

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Joint cartilage damage affects 10-12% of the world's population. Medical treatments improve the short-term quality of life of affected individuals but lack a long-term effect due to injury progression into fibrocartilage. The use of mesenchymal stem cells (MSCs) is one of the most promising strategies for tissue regeneration due to their ability to be isolated, expanded and differentiated into metabolically active chondrocytes to achieve long-term restoration. For this purpose, human adipose-derived MSCs (Ad-MSCs) were isolated from lipectomy and grown in xeno-free conditions. To establish the best differentiation potential towards a stable chondrocyte phenotype, isolated Ad-MSCs were sequentially exposed to five differentiation schemes of growth factors in previously designed three-dimensional biphasic scaffolds with incorporation of a decellularized cartilage matrix as a bioactive ingredient, silk fibroin and bone matrix, to generate a system capable of being loaded with pre-differentiated Ad-MSCs, to be used as a clinical implant in cartilage lesions for tissue regeneration. Chondrogenic and osteogenic markers were analyzed by reverse transcription-quantitative PCR and cartilage matrix generation by histology techniques at different time points over 40 days. All groups had an increased expression of chondrogenic markers; however, the use of fibroblast growth factor 2 (10 ng/ml) followed by a combination of insulin-like growth factor 1 (100 ng/ml)/TGFβ1 (10 ng/ml) and a final step of exposure to TGFβ1 alone (10 ng/ml) resulted in the most optimal chondrogenic signature towards chondrocyte differentiation and the lowest levels of osteogenic expression, while maintaining stable collagen matrix deposition until day 33. This encourages their possible use in osteochondral lesions, with appropriate properties for use in clinical patients.

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“…IGF-1 has been reported showing high anabolic effects and decrease in catabolic responses in articular cartilage metabolism in vitro [167,168]. Other studies have reported using different growth factors which were successful in producing several features that resembled typical articular cartilage [169][170][171]. Despite the capacity to promote cartilage matrix formation, growth factors have shown some drawbacks with IGF-1 associated with a loss of chondrocyte phenotype and extracellular matrix breakdown [168].…”

Section: Biochemical and Biomechanical Stimulationmentioning

confidence: 99%

“…Despite the capacity to promote cartilage matrix formation, growth factors have shown some drawbacks with IGF-1 associated with a loss of chondrocyte phenotype and extracellular matrix breakdown [168]. Furthermore, IGF-1 in human MSCs inhibited collagen II expression and overexpression can induce hypertrophic differentiation and mineralisation [172].…”

Section: Biochemical and Biomechanical Stimulationmentioning

confidence: 99%

Biological perspectives and current biofabrication strategies in osteochondral tissue engineering

et al. 2020

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Articular cartilage and the underlying subchondral bone are crucial in human movement and when damaged through disease or trauma impacts severely on quality of life. Cartilage has a limited regenerative capacity due to its avascular composition and current therapeutic interventions have limited efficacy. With a rapidly ageing population globally, the numbers of patients requiring therapy for osteochondral disorders is rising, leading to increasing pressures on healthcare systems. Research into novel therapies using tissue engineering has become a priority. However, rational design of biomimetic and clinically effective tissue constructs requires basic understanding of osteochondral biological composition, structure, and mechanical properties. Furthermore, consideration of material design, scaffold architecture, and biofabrication strategies, is needed to assist in the development of tissue engineering therapies enabling successful translation into the clinical arena. This review provides a starting point for any researcher investigating tissue engineering for osteochondral applications. An overview of biological properties of osteochondral tissue, current clinical practices, the role of tissue engineering and biofabrication, and key challenges associated with new treatments is provided. Developing precisely engineered tissue constructs with mechanical and phenotypic stability is the goal. Future work should focus on multi-stimulatory environments, long-term studies to determine phenotypic alterations and tissue formation, and the development of novel bioreactor systems that can more accurately resemble the in vivo environment.

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A Bioactive Cartilage Graft of IGF1-Transduced Adipose Mesenchymal Stem Cells Embedded in an Alginate/Bovine Cartilage Matrix Tridimensional Scaffold

Cited by 6 publications

References 51 publications

A Cellularized Biphasic Implant Based on a Bioactive Silk Fibroin Promotes Integration and Tissue Organization during Osteochondral Defect Repair in a Porcine Model

A Cellularized Biphasic Implant Based on a Bioactive Silk Fibroin Promotes Integration and Tissue Organization during Osteochondral Defect Repair in a Porcine Model

Sequential growth factor exposure of human Ad‑MSCs improves chondrogenic differentiation in an osteochondral biphasic implant

Biological perspectives and current biofabrication strategies in osteochondral tissue engineering

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