Meniscus-Derived Matrix Scaffolds Promote the Integrative Repair of Meniscal Defects

Ruprecht, Jacob C.; Waanders, Taylor D.; Rowland, Christopher R.; Nishimuta, James F.; Glass, Katherine A.; Stencel, Jennifer; DeFrate, Louis E.; Guilak, Farshid; Weinberg, J. Brice; McNulty, Amy L.

doi:10.1038/s41598-019-44855-3

Cited by 34 publications

(63 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We used our in vitro meniscus repair model system [18,19,[33][34][35][36][37][38][39] to study the integrative repair of acellular MDM scaffolds with meniscus tissue [19]. After 14 days in culture, constructs were analyzed by fluorescence imaging, biochemical analyses, mechanical testing, and histology.…”

Section: Meniscus Repair Model Systemmentioning

confidence: 99%

“…Push-out testing was used to quantify the integrative shear strength of repair [18,19,[33][34][35][36][37][38][39] between the MDM scaffolds and meniscus tissue after 14 days in culture. The integrative shear strength of repair increased with the concentration of MDM in the scaffolds, such that 16% > 12% > 8% ( Figure 5, p < 0.005).…”

Section: Integrative Shear Strength Of Repairmentioning

confidence: 99%

“…Tissue-derived scaffolds provide an attractive approach for enhancing meniscus repair by providing a scaffold composed of native extracellular matrix (ECM) components that may promote integrative repair with the endogenous injured meniscus tissue [4,5,[17][18][19]. Tissue-derived scaffolds contain tissue-specific growth factors that may facilitate cell infiltration and proliferation, as well as matrix synthesis with minimal need for exogenous growth factors [17,[19][20][21][22][23]. Our earlier work demonstrated the ability of meniscus-derived matrix (MDM) scaffolds to promote endogenous meniscus cell migration and enhance the integrative repair of an in vitro meniscus defect [19].…”

Section: Introductionmentioning

confidence: 99%

“…Tissue-derived scaffolds contain tissue-specific growth factors that may facilitate cell infiltration and proliferation, as well as matrix synthesis with minimal need for exogenous growth factors [17,[19][20][21][22][23]. Our earlier work demonstrated the ability of meniscus-derived matrix (MDM) scaffolds to promote endogenous meniscus cell migration and enhance the integrative repair of an in vitro meniscus defect [19]. In particular, we determined that 8% MDM scaffolds enhanced meniscus repair as compared to 4% MDM scaffolds, suggesting that higher percentages of MDM may further improve meniscus repair.…”

Section: Introductionmentioning

confidence: 99%

“…In order to enhance the integrity and mechanical properties of biomaterial scaffolds, a variety of cross-linking strategies have been evaluated, including both physical and chemical cross-linking methods [19,[23][24][25][26][27][28][29]. Physical cross-linking methods include dehydrothermal (DHT) treatment [18,19,23,25,29] and exposure to ultraviolet (UV) light [25,26,29], while chemical cross-linking can be achieved with glutaraldehyde [27,28] and genipin [24,30]. DHT cross-linking is known to mediate uniaxial tensile strength of collagen scaffolds [25] and to increase cellular proliferation and proteoglycan production when compared to UV cross-linking of cartilage-derived matrix (CDM) scaffolds [23].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Meniscus-Derived Matrix Bioscaffolds: Effects of Concentration and Cross-Linking on Meniscus Cellular Responses and Tissue Repair

Lyons

Perea

Weinberg

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

Meniscal injuries, particularly in the avascular zone, have a low propensity for healing and are associated with the development of osteoarthritis. Current meniscal repair techniques are limited to specific tear types and have significant risk for failure. In previous work, we demonstrated the ability of meniscus-derived matrix (MDM) scaffolds to augment the integration and repair of an in vitro meniscus defect. The objective of this study was to determine the effects of percent composition and dehydrothermal (DHT) or genipin cross-linking of MDM bioscaffolds on primary meniscus cellular responses and integrative meniscus repair. In all scaffolds, the porous microenvironment allowed for exogenous cell infiltration and proliferation, as well as endogenous meniscus cell migration. The genipin cross-linked scaffolds promoted extracellular matrix (ECM) deposition and/or retention. The shear strength of integrative meniscus repair was improved with increasing percentages of MDM and genipin cross-linking. Overall, the 16% genipin cross-linked scaffolds were most effective at enhancing integrative meniscus repair. The ability of the genipin cross-linked scaffolds to attract endogenous meniscus cells, promote glycosaminoglycan and collagen deposition, and enhance integrative meniscus repair reveals that these MDM scaffolds are promising tools to augment meniscus healing.

show abstract

Section: Meniscus Repair Model Systemmentioning

confidence: 99%

Section: Integrative Shear Strength Of Repairmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Meniscus-Derived Matrix Bioscaffolds: Effects of Concentration and Cross-Linking on Meniscus Cellular Responses and Tissue Repair

Lyons

Perea

Weinberg

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

Cyclic freeze–thaw grinding to decellularize meniscus for fabricating porous, elastic scaffolds

Ding

Zhang

Sun

et al. 2022

J Biomedical Materials Res

View full text Add to dashboard Cite

Decellularized meniscus extracellular matrix (dmECM)‐based biological scaffolds in the forms of sponge, hydrogel, nanofiber, and composite have gained increasing interest in meniscus tissue engineering and regeneration. A common shortcoming of those scaffolds is insufficient mechanical strength and poor elasticity. Herein, we report a practicable protocol for milder meniscus decellularization to prepare elastic, porous dmECM scaffolds. Porcine meniscus was pulverized by cyclic freeze–thaw grinding and then treated with DNase to obtain fine dmECM particles. Individual dmECM particles were condensed to bulk preparation by centrifuge, followed by lyophilization to form blocks, and finally crosslinked by dehydrothermal treatment to obtain porous dmECM scaffolds. Our results show that the freeze–thaw grinding method was effective in removing cellular DNA with good retention of meniscus‐derived bioactive components. The dmECM scaffold had porous structure with interconnected mesopores and good mechanical properties. Primary articular chondrocytes proliferated robustly and maintained chondrogenic characteristics and produce abundant collagen on dmECM scaffolds. Evaluation of biocompatibility in a rat model shows that the dmECM scaffold elicited minor foreign body reactions, indicating effective antigen removal from dmECM. This study provides an alternative for preparing dmECM and fabricating porous scaffolds for meniscus repair and regeneration.

show abstract

Meniscus cell regional phenotypes: Dedifferentiation and reversal by biomaterial embedding

Andress

Kim

Cutcliffe

et al. 2020

Journal Orthopaedic Research

Self Cite

View full text Add to dashboard Cite

Meniscus injuries are common and a major cause of long-term joint degeneration and disability. Current treatment options are limited, so novel regenerative therapies or tissue engineering strategies are urgently needed. The development of new therapies is hindered by a lack of knowledge regarding the cellular biology of the meniscus and a lack of well-established methods for studying meniscus cells in vitro.The goals of this study were to (1) establish baseline expression profiles and dedifferentiation patterns of inner and outer zone primary meniscus cells, and(2) evaluate the utility of poly(ethylene glycol) diacrylate (PEGDA) and gelatin methacrylate (GelMA) polymer hydrogels to reverse dedifferentiation trends for long-term meniscus cell culture. Using reverse transcription-quantitative polymerase chain reaction, we measured expression levels of putative meniscus phenotype marker genes in freshly isolated meniscus tissue, tissue explant culture, and monolayer culture of inner and outer zone meniscus cells from porcine knees to establish baseline dedifferentiation characteristics, and then compared these expression levels to PEGDA/GelMA embedded passaged meniscus cells. COL1A1 showed robust upregulation, while CHAD, CILP, and COMP showed downregulation with monolayer culture. Expression levels of COL2A1, ACAN, and SOX9 were surprisingly similar between inner and outer zone tissue and were found to be less sensitive as markers of dedifferentiation. When embedded in PEGDA/GelMA hydrogels, expression levels of meniscus cell phenotype genes were significantly modulated by varying the ratio of polymer components, allowing these materials to be tuned for phenotype restoration, meniscus cell culture, and tissue engineering applications.

show abstract

Meniscus-Derived Matrix Scaffolds Promote the Integrative Repair of Meniscal Defects

Cited by 34 publications

References 64 publications

Meniscus-Derived Matrix Bioscaffolds: Effects of Concentration and Cross-Linking on Meniscus Cellular Responses and Tissue Repair

Meniscus-Derived Matrix Bioscaffolds: Effects of Concentration and Cross-Linking on Meniscus Cellular Responses and Tissue Repair

Cyclic freeze–thaw grinding to decellularize meniscus for fabricating porous, elastic scaffolds

Meniscus cell regional phenotypes: Dedifferentiation and reversal by biomaterial embedding

Contact Info

Product

Resources

About