Biomechanically and biochemically functional scaffold for recruitment of endogenous stem cells to promote tendon regeneration

Cui, Jing; Ning, Liang-Ju; Wu, Fei-Peng; Hu, Ruo-Nan; Li, Xuan; He, Shu-Kun; Zhang, Yanjing; Luo, Jia-Jiao; Luo, Jingcong; Qin, Tingwu

doi:10.1038/s41536-022-00220-z

Cited by 13 publications

(15 citation statements)

References 73 publications

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“…Because the body structure of nonhuman primates is closer to that of humans, 3D-CH-IB-ST needs to be implanted in the TBI model of non-human primates to evaluate the effect of 3D-CH-IB-ST on TBI repair before clinical trials. It is worthwhile to perform further research on the modification of chemical cross-linking and the enhancement of physical qualities in the creation of scaffolds [61][62][63][64][65][66].…”

Section: Discussionmentioning

confidence: 99%

3D printing of injury-preconditioned secretome/collagen/heparan sulfate scaffolds for neurological recovery after traumatic brain injury in rats

et al. 2022

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Background The effects of traumatic brain injury (TBI) can include physical disability and even death. The development of effective therapies to promote neurological recovery is still a challenging problem. 3D-printed biomaterials are considered to have a promising future in TBI repair. The injury-preconditioned secretome derived from human umbilical cord blood mesenchymal stem cells showed better stability in neurological recovery after TBI. Therefore, it is reasonable to assume that a biological scaffold loaded with an injury-preconditioned secretome could facilitate neural network reconstruction after TBI. Methods In this study, we fabricated injury-preconditioned secretome/collagen/heparan sulfate scaffolds by 3D printing. The scaffold structure and porosity were examined by scanning electron microscopy and HE staining. The cytocompatibility of the scaffolds was characterized by MTT analysis, HE staining and electron microscopy. The modified Neurological Severity Score (mNSS), Morris water maze (MWM), and motor evoked potential (MEP) were used to examine the recovery of cognitive and locomotor function after TBI in rats. HE staining, silver staining, Nissl staining, immunofluorescence, and transmission electron microscopy were used to detect the reconstruction of neural structures and pathophysiological processes. The biocompatibility of the scaffolds in vivo was characterized by tolerance exposure and liver/kidney function assays. Results The excellent mechanical and porosity characteristics of the composite scaffold allowed it to efficiently regulate the secretome release rate. MTT and cell adhesion assays demonstrated that the scaffold loaded with the injury-preconditioned secretome (3D-CH-IB-ST) had better cytocompatibility than that loaded with the normal secretome (3D-CH-ST). In the rat TBI model, cognitive and locomotor function including mNSS, MWM, and MEP clearly improved when the scaffold was transplanted into the damage site. There is a significant improvement in nerve tissue at the site of lesion. More abundant endogenous neurons with nerve fibers, synaptic structures, and myelin sheaths were observed in the 3D-CH-IB-ST group. Furthermore, the apoptotic response and neuroinflammation were significantly reduced and functional vessels were observed at the injury site. Good exposure tolerance in vivo demonstrated favorable biocompatibility of the scaffold. Conclusions Our results demonstrated that injury-preconditioned secretome/collagen/heparan sulfate scaffolds fabricated by 3D printing promoted neurological recovery after TBI by reconstructing neural networks, suggesting that the implantation of the scaffolds could be a novel way to alleviate brain damage following TBI. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

3D printing of injury-preconditioned secretome/collagen/heparan sulfate scaffolds for neurological recovery after traumatic brain injury in rats

et al. 2022

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“…Deeken et al, 10 in 2011, reported that decellularization using tri (n‐butyl) phosphate (1%) was found to be more effective in decellularization than other chemicals, including peracetic acid, sodium dodecyl sulfate, and so forth, preserving the structure and ECM composition intact. Receullarisation approaches using decellularized bovine tendon sheets with ECM from tendon‐derived stem cells to fabricate biomechanically and biochemically functional scaffolds providing a microenvironment for tendon regeneration 11 and preclinical trials in rat models using decellularized scaffolds 12 have been reported.…”

Section: Introductionmentioning

confidence: 99%

“…Receullarisation approaches using decellularized bovine tendon sheets with ECM from tendon-derived stem cells to fabricate biomechanically and biochemically functional scaffolds providing a microenvironment for tendon regeneration 11 and preclinical trials in rat models using decellularized scaffolds 12 have been reported.…”

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confidence: 99%

Natural 3D Extra Cellular Matrix mimicking stem cells seeded decellularized scaffolds as a platform for tendon regeneration

John

Joseph

et al. 2023

J Biomed Mater Res

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Achilles tendon, which connects the calf muscles to heel, is the strongest tendon in the body. Despite its strength, it is more prone to injury due to its limited blood supply. Tendon-related injuries are more common in sportspersons, people with laborintensive work and the aged community. The currently available treatment mode is surgery which is expensive with chances of re-injury. Present study made an attempt to fabricate a tissue-engineered tendon product using decellularized tendon (DT) seeded with stem cells and bioactive components of Tinospora cordifolia extract (TCE). The bare DT tissue scaffold/substitute may also serve as a drug delivery platform for growth factors and cells with a new approach to promote tissue regeneration in clinical applications. DT construct showed good regenerative potential and easily promoted new tissue formation. Decellularization of the tendon was carried out by chemical method using tri (n-butyl) phosphate (TnBP). DT was physicochemically characterized by contact angle measurement, thermal gravimetric analysis (TGA), and mechanical testing. Rabbit adipose derived mesenchymal stem cells (RADMSCs) were isolated and phenotypically characterized by flow cytometry analysis, tri lineage differentiation, and so forth. Further, stem cell seeded DT scaffolds were prepared and found to be non-toxic by cytotoxicity, cell adhesion by scanning electron microscope (SEM) analysis, cell viability by live dead assays, and so forth.The findings of this study yield valid proof for the employability of cell-seeded DT construct as a natural scaffold in repairing injured tendons-the toughest chords of the skeleton. This is a cost effective method for the replacement of injured/damaged tendons for athletes, people in labor-intensive occupations, the elderly population, and so forth-a boon towards the repair of the tendon in damage/injury.

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Section: Introductionmentioning

confidence: 99%

“…Decellularized tendon scaffolds have great potential for tendon repair [ 9 ]. They have been shown to maintain the tissue biomechanical properties and composition, including tendon-specific structural proteins, growth factors, and cytokines [ 9 , 10 ]. However, for their clinical application, decellularized tendon scaffolds still have many drawbacks, such as cell source, ex vivo regeneration [ 11 ], limited shapes, and donor shortage.…”

Section: Introductionmentioning

confidence: 99%

Decellularized Extracellular Matrix-Based Bioinks for Tendon Regeneration in Three-Dimensional Bioprinting

Khalak

García‐Villén

Ruiz‐Alonso

et al. 2022

IJMS

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In the last few years, attempts to improve the regeneration of damaged tendons have been rising due to the growing demand. However, current treatments to restore the original performance of the tissue focus on the usage of grafts; although, actual grafts are deficient because they often cannot provide enough support for tissue regeneration, leading to additional complications. The beneficial effect of combining 3D bioprinting and dECM as a novel bioink biomaterial has recently been described. Tendon dECMs have been obtained by using either chemical, biological, or/and physical treatments. Although decellularization protocols are not yet standardized, recently, different protocols have been published. New therapeutic approaches embrace the use of dECM in bioinks for 3D bioprinting, as it has shown promising results in mimicking the composition and the structure of the tissue. However, major obstacles include the poor structural integrity and slow gelation properties of dECM bioinks. Moreover, printing parameters such as speed and temperature have to be optimized for each dECM bioink. Here, we show that dECM bioink for 3D bioprinting provides a promising approach for tendon regeneration for future clinical applications.

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Biomechanically and biochemically functional scaffold for recruitment of endogenous stem cells to promote tendon regeneration

Cited by 13 publications

References 73 publications

3D printing of injury-preconditioned secretome/collagen/heparan sulfate scaffolds for neurological recovery after traumatic brain injury in rats

3D printing of injury-preconditioned secretome/collagen/heparan sulfate scaffolds for neurological recovery after traumatic brain injury in rats

Natural 3D Extra Cellular Matrix mimicking stem cells seeded decellularized scaffolds as a platform for tendon regeneration

Decellularized Extracellular Matrix-Based Bioinks for Tendon Regeneration in Three-Dimensional Bioprinting

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