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A novel construct with biomechanical flexibility for articular cartilage regeneration.

ABSTRACT: BACKGROUND:Although tissue-engineered cartilage has been broadly studied, complete integration of regenerated cartilage with residual cartilage is still difficult for the inferior mechanical and biochemical feature of neocartilage. Chondrogenesis of mesenchymal stem cells can be induced by biophysical and biochemical factors. METHODS:In this study, autologous platelet-rich fibrin (PRF) membrane was used as a growth factor-rich scaffold that may facilitate differentiation of the transplanted bone marrow mesenchymal stem cells (BMSCs). At the same time, hydrostatic pressure was adopted for pre-adjustment of the seed cells before transplantation that may promote the mechanical flexibility of neocartilage. RESULTS:An in vitro study showed that the feasible hydrostatic pressure stimulation substantially promoted the chondrogenic potential of in vitro-cultured BMSC/PRF construct. In vivo results revealed that at every time point, the newborn tissues were the most favorable in the pressure-pretreated BMSC/PRF transplant group. Besides, the transplantation of feasible hydrostatic pressure-pretreated construct by BMSC sheet fragments and PRF granules could obviously improve the integration between the regenerated cartilage and host cartilage milieu, and thereby achieve boundaryless repair between the neocartilage and residual host cartilage tissue in rabbit temporomandibular joints. It could be concluded that feasible hydrostatic pressure may effectively promote the proliferation and chondrogenic differentiation of BMSCs in a BMSC/PRF construct. CONCLUSION:This newly formed construct with biomechanical flexibility showed a superior capacity for cartilage regeneration by promoting the mechanical properties and integration of neocartilage.

SUBMITTER: Cheng B

PROVIDER: S-EPMC6757433 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A novel construct with biomechanical flexibility for articular cartilage regeneration.

Cheng Baixiang B Tu Teng T Shi Xiao X Liu Yanzheng Y Zhao Ying Y Zhao Yinhua Y Li Yijie Y Chen Hui H Chen Yongjin Y Zhang Min M

Stem cell research & therapy 20190923 1

<h4>Background</h4>Although tissue-engineered cartilage has been broadly studied, complete integration of regenerated cartilage with residual cartilage is still difficult for the inferior mechanical and biochemical feature of neocartilage. Chondrogenesis of mesenchymal stem cells can be induced by biophysical and biochemical factors.<h4>Methods</h4>In this study, autologous platelet-rich fibrin (PRF) membrane was used as a growth factor-rich scaffold that may facilitate differentiation of the tr ...[more]

PMID: 31547887

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Project description:Articular cartilage has limited capacity for regeneration and when damaged cannot be repaired with currently available metallic or synthetic implants. We aim to bioengineer a microfibre-reinforced hydrogel that can capture the zonal depth-dependent mechanical properties of native cartilage, and simultaneously support neo-cartilage formation. With this goal, a sophisticated bi-layered microfibre architecture, combining a densely distributed crossed fibre mat (superficial tangential zone, STZ) and a uniform box structure (middle and deep zone, MDZ), was successfully manufactured via melt electrospinning and combined with a gelatin-methacrylamide hydrogel. The inclusion of a thin STZ layer greatly increased the composite construct's peak modulus under both incongruent (3.2-fold) and congruent (2.1-fold) loading, as compared to hydrogels reinforced with only a uniform MDZ structure. Notably, the stress relaxation response of the bi-layered composite construct was comparable to the tested native cartilage tissue. Furthermore, similar production of sulphated glycosaminoglycans and collagen II was observed for the novel composite constructs cultured under mechanical conditioning w/o TGF-ß1 supplementation and in static conditions w/TGF-ß1 supplementation, which confirmed the capability of the novel composite construct to support neo-cartilage formation upon mechanical stimulation. To conclude, these results are an important step towards the design and manufacture of biomechanically competent implants for cartilage regeneration. STATEMENT OF SIGNIFICANCE: Damage to articular cartilage results in severe pain and joint disfunction that cannot be treated with currently available implants. This study presents a sophisticated bioengineered bi-layered fibre reinforced cell-laden hydrogel that can approximate the functional mechanical properties of native cartilage. For the first time, the importance of incorporating a viable superficial tangential zone (STZ) - like structure to improve the load-bearing properties of bioengineered constructs, particularly when in-congruent surfaces are compressed, is demonstrated. The present work also provides new insights for the development of implants that are able to promote and guide new cartilaginous tissue formation upon physiologically relevant mechanical stimulation.

Project description:An exact understanding of the interplay between the articulating tissues of the knee joint in relation to the osteoarthritis (OA)-related degeneration process is of considerable interest. Therefore, the aim of the present study was to characterize the biomechanical properties of mildly and severely degenerated human knee joints, including their menisci and tibial and femoral articular cartilage (AC) surfaces. A spatial biomechanical mapping of the articulating knee joint surfaces of 12 mildly and 12 severely degenerated human cadaveric knee joints was assessed using a multiaxial mechanical testing machine. To do so, indentation stress relaxation tests were combined with thickness and water content measurements at the lateral and medial menisci and the AC of the tibial plateau and femoral condyles to calculate the instantaneous modulus (IM), relaxation modulus, relaxation percentage, maximum applied force during the indentation, and the water content. With progressing joint degeneration, we found an increase in the lateral and the medial meniscal instantaneous moduli (p < 0.02), relaxation moduli (p < 0.01), and maximum applied forces (p < 0.01), while for the underlying tibial AC, the IM (p = 0.01) and maximum applied force (p < 0.01) decreased only at the medial compartment. Degeneration had no influence on the relaxation percentage of the soft tissues. While the water content of the menisci did not change with progressing degeneration, the severely degenerated tibial AC contained more water (p < 0.04) compared to the mildly degenerated tibial cartilage. The results of this study indicate that degeneration-related (bio-)mechanical changes seem likely to be first detectable in the menisci before the articular knee joint cartilage is affected. Should these findings be further reinforced by structural and imaging analyses, the treatment and diagnostic paradigms of OA might be modified, focusing on the early detection of meniscal degeneration and its respective treatment, with the final aim to delay osteoarthritis onset.

Project description:BackgroundRegeneration of articular cartilage poses a tremendous challenge due to its limited self-repair capability and inflammation at the damaged site. To generate the desired structures that mimic the structure of native tissue, microtissues with repeated functional units such as cell aggregates have been developed. Multicellular aggregates of mesenchymal stem cells (MSCs) can be used as microscale building blocks of cartilage due to their potential for cell-cell contact, cell proliferation, and differentiation.MethodsChondrogenic microtissues were developed through incorporation of kartogenin-releasing poly (lactic-co-glycolic acid) (PLGA) microparticles (KGN-MP) within the MSC aggregates. The chondrogenic potential of KGN-MP treated MSC aggregates was proven in vitro by studying the chondrogenic markers at the RNA level and histological analysis. In order to address the inflammatory responses at the defect site, the microtissues were delivered in vivo via an injectable, anti-inflammatory hydrogel that contained gelatin methacryloyl (GelMA) loaded with curcumin (Cur).ResultsThe KGN-MPs were fabricated to support MSCs during cartilage differentiation. According to real-time RT-PCR analysis, the presence of KGN in the aggregates led to the expression of cartilage markers by the MSCs. Both toluidine blue (TB) and safranin O (SO) staining demonstrated homogeneous glycosaminoglycan production throughout the KGN-MP incorporated MSC aggregates. The curcumin treatment efficiently reduced the expressions of hypertrophy markers by MSCs in vitro. The in vivo results showed that implantation of chondrogenic microtissues (KGN-MP incorporated MSC aggregates) using the curcumin loaded GelMA hydrogel resulted in cartilage tissue regeneration that had characteristic features close to the natural hyaline cartilage according to observational and histological results.ConclusionsThe use of this novel construct that contained chondrogenic cell blocks and curcumin is highly desired for cartilage regeneration.

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A novel construct with biomechanical flexibility for articular cartilage regeneration.

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A novel construct with biomechanical flexibility for articular cartilage regeneration.

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