The revitalisation of flexor tendon allografts with bone marrow stromal cells and mechanical stimulation

Wu, Jingheng; Thoreson, Andrew R.; Gingery, Anne; An, Kai Nan; Moran, Steven L.; Amadio, Peter C.; Zhao, Chunfeng

doi:10.1302/2046-3758.63.bjr-2016-0207.r1

Cited by 11 publications

(12 citation statements)

References 25 publications

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“…The confined environment created by the high natural polydispersity of Cr in the culture medium accelerates cleavage of the N‐ and C ‐ propeptides of the procollagen molecules by the N‐ and C ‐ proteinases, thereby creating the insoluble collagen molecule (40, 41). COL1A1 was not increased at 10% strain, which contradicts previous studies in which mechanical stimulation led to increased COL1A1 synthesis in TCs (82, 87–89) and BMSCs (30, 90, 91), a process mediated by TGF‐β1 (92). Increased deposition of collagen types III, IV, V, and VI has been observed in fibroblasts (41), and increased deposition of collagen III has been described in BMSCs (47) and corneal fibroblasts (42) when using Cr as a crowder.…”

Section: Resultscontrasting

confidence: 89%

Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes

2019

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Bottom‐up bioengineering utilizes the inherent capacity of cells to build highly sophisticated structures with high levels of biomimicry. Despite the significant advancements in the field, monodomain approaches require prolonged culture time to develop an implantable device, usually associated with cell phenotypic drift in culture. Herein, we assessed the simultaneous effect of macromolecular crowding (MMC) and mechanical loading in enhancing extracellular matrix (ECM) deposition while maintaining tenocyte (TC) phenotype and differentiating bone marrow stem cells (BMSCs) or transdifferentiating neonatal and adult dermal fibroblasts toward tenogenic lineage. At d 7, all cell types presented cytoskeleton alignment perpendicular to the applied load independently of the use of MMC. MMC enhanced ECM deposition in all cell types. Gene expression analysis indicated that MMC and mechanical loading maintained TC phenotype, whereas tenogenic differentiation of BMSCs or transdifferentiation of dermal fibroblasts was not achieved. Our data suggest that multifactorial bottom‐up bioengineering approaches significantly accelerate the development of biomimetic tissue equivalents.—Gaspar, D., Ryan, C. N. M., Zeugolis, D. I. Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes. FASEB J. 33, 5741–5754 (2019). http://www.fasebj.org

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Section: Resultscontrasting

confidence: 89%

Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes

2019

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“…Second, we did not mechanically evaluate these samples in this study. Our prior study indicates that no significant difference in mechanical characteristics among normal tendon, LSDCT, and LSDCT + BMSCs was observed after 2 weeks of culture in vitro [19]. Also, the mechanical evaluation of tendon samples under ex vivo situation does not reflect the actual physiological condition after tendon or ligament reconstruction.…”

Section: Discussionmentioning

confidence: 93%

“…Furthermore, the volardorsal slits were shallow because of the oval shape of the flexor tendon cross-section. More recently, a lateral tendon slit technique was introduced to seed bone marrow stromal cells (BMSCs) to enhance the revitalization of DCT graft [19]. The result revealed that the seeded BMSCs (2 × 10 7 cells/mL) remained viable and would repopulate in the DCT graft after 2 weeks of culture.…”

Section: Introductionmentioning

confidence: 99%

Lateral slit delivery of bone marrow stromal cells enhances regeneration in the decellularized allograft flexor tendon

Zhang

Amadio

et al. 2019

Journal of Orthopaedic Translation

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Background/objectiveStem cell–based therapy has been applied to accelerate the revitalization of allograft tendon into a viable and functional tendon. Although many authors have proposed different methods to help the seeded stem cell distribution in the decellularized allograft, limited success has been achieved as tendon is a high dense connective tissue. We hypothesized that bone marrow stromal cells (BMSCs), seeded through the lateral slit, can regenerate the decellularized tendon (DCT) graft. The cell proliferation, cell viability, and tendon-specific gene expression are increased with the seeded cell density.MethodsEighty-seven flexor digitorum profundus tendons were equally and randomly divided into 6 treatment groups that were seeded with low-density (2 × 107 cells/mL) and high-density (5 × 107 cells/mL) BMSCs through lateral slits cultured for 2 and 4 weeks, DCT without cells, and fresh live tendons. Tendons were evaluated for cell distribution, cell proliferation, cell viability, gene expression of Collagen I and Collagen III, tenogenic markers, and MMPs.ResultsHistologic evaluation revealed BMSCs distributed from the lateral slit to the whole DCT. BMSCs were proliferated and kept viable in lateral slit decellularized tendon (LSDCT) in both seeded cell density groups after 2 and 4 weeks of culture. However, no significant differences in the cell proliferation between both cell density groups at 2 and 4 weeks of culture were observed. The lowest cell viability was found in the high-density group after 4 weeks of culture. BMSCs in LSDCT showed a significant tendency of higher gene expression of Collagen I, Collagen III, tenascin C, MMP2, MMP9, and MMP13 compared to normal tendons in both cell density groups at 2 and 4 weeks of culture.ConclusionBMSCs proliferated and remained viable after 2 and 4 weeks of culture with distribution throughout the lateral slits. Lateral slit preparation allows for the effective delivery and maintenance of mesenchymal cells with proliferation and generating a tenogenic behaviour of DCT in both the low and high cell densities in an in vitro model.The translation potential of this articleRevitalizing the implanted decellularized allograft is important for clinical application. In this study, we demonstrated that the DCT, with lateral slits, could harbour the seeded stem cell and stimulate proliferation with collagen synthesis. This evidence was presented for clinical application of the lateral slit technique, in DCT grafts, which would repopulate the seeded BMSCs during tendon and ligament reconstruction.

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“…). The cell density was chosen based on the previous reports . After cell seeding, the tendon was treated with cd‐SYN of the following formula: 46% native synovial fluid, 10% gelatin (Sigma), 1% 1‐ethyl‐3‐([3‐dimethylaminopropyl] carbodiimide hydrochloride) (Sigma), and 1% N‐hydroxysuccinimide (Sigma) in 0.1 M of 2‐[N‐morpholino] ethanesulfonic acid buffer (Sigma) (pH, 6.0).…”

Section: Methodsmentioning

confidence: 99%

Revitalized and synovialized allograft for intrasynovial flexor tendon reconstruction in an in vivo canine model

Zhang

Reisdorf

et al. 2018

Journal Orthopaedic Research

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This study was to test our hypothesis that flexor tendon reconstruction with an allograft revitalized with bone marrow stromal cells (BMSCs) and synovialized with carbodiimide derivatized autologous synovial fluid (cd-SYN) would result in better digit functional restoration than the conventional allograft tendon. A total of 32 flexor digital profundus tendons from the second and fifth digit of 16 dogs were created a repair failure model first. Then, failed-repaired tendons were reconstructed with either a revitalized-synovialized allograft tendon or a clinical standard autograft tendon (control group). The allograft tendon was seeded with autologous BMSCs in multiple slits and the graft surface was coated with cd-SYN. A 6 weeks after tendon reconstruction, the digits were harvested and evaluated for digit function, adhesion status, tendon gliding resistance, attachment strength, cell viability, and histologic factors. The allograft group had significantly improved digit function compared with the control group through decreased work of flexion, increased digit range of motion under 2-Newton force, and less adhesion score (p < .05). However, the distal attachment-site strength and stiffness in the allograft tendon were significantly weaker than the autografts (p < .05). No significant difference was found for gliding resistance. Histologically, allograft tendons coated with allograft had smoother surfaces and showed tendon-to-bone and tendon-to-tendon incorporation. Viable BMSCs were found in the tendon slits 6 weeks after the graft. In conclusion, cellular lubricant-based modification of allograft tendons improved digit function and reduced the adhesions compared with autograft for flexor tendon reconstruction. However, improvement of graft-to-host tendon healing is still challenging. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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The revitalisation of flexor tendon allografts with bone marrow stromal cells and mechanical stimulation

Cited by 11 publications

References 25 publications

Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes

Multifactorial bottom‐up bioengineering approaches for the development of living tissue substitutes

Lateral slit delivery of bone marrow stromal cells enhances regeneration in the decellularized allograft flexor tendon

Revitalized and synovialized allograft for intrasynovial flexor tendon reconstruction in an in vivo canine model

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