A Biomaterial‐Based Hedging Immune Strategy for Scarless Tendon Healing

Abstract

Figure 4. Effects of Him-MFM on inflammation damaging and apoptotic stress and mobilized tenocyte functional proliferation. a) Immunohistochemical staining and evaluation of IL-1β and TNF-α expression in peritendinous adhesion area for 5 and 10 days. Scale bars: 5 µm. b) The positive area percent of IL-1β and TNF-α for 5 and 10 days (n = 6). c) Immunofluorescence staining for CD68 + macrophages, Ly6G + neutrophils, and DAPI. Scale bars: 5 µm. d) The number of macrophages and neutrophils in LPF at series time post injury. ***p < 0.001 compared to control group. ### p < 0.001 compared to MFM group. † † † p < 0.001 compared to glucocorticoid group. ‡ ‡ ‡ p < 0.001 compared to the NSAIDS group (n = 6). e) The stub and sheath of tendon post injury. f) Immunofluorescence staining for TUNEL positive apoptosis cells, Scx + tenocytes, and DAPI. Scale bars, 5 µm. g) Positive percent of apoptotic cells on tendon stub and sheath (n = 6). ***p < 0.001. h) Immunofluorescence staining for Ki67, Scx + tenocytes, and DAPI. Scale bars: 5 µm.i) Amount of Ki67 + cells between stubs of sagittal section (n = 6). ***p < 0.001 compared to control group. ### p < 0.001 compared to MFM group. † † † p < 0.001 compared to glucocorticoid group. ‡ ‡ ‡ p < 0.001 compared to the NSAIDS group. j) Percent of Ki67 + tenocyte of sagittal section, n = 6 biologically independent samples per group. ***p < 0.001. Data are presented as mean ± SD. Statistical analysis was performed by two-tailed Student's t test.

Wnt3a-Modified Nanofiber Scaffolds Facilitate Tendon Healing by Driving Macrophage Polarization during Repair

“…Fascial flap transposition, tendon transposition, or tendon graft may be required for a defect of the same length in human patients to bridge the defect at the broken end of the Achilles tendon. − In this experiment, our hypothesis was confirmed by the immunofluorescence staining results, i.e., the Wnt3a-modified tendon-repair scaffolds promoted the forward shift of the total macrophage counting curve during tendon regeneration in rats, and the number of macrophages in the Wnt3a group peaked at approximately 2 weeks and was equivalent to that in the control group at 4 weeks. The similar forward shift of the curve may indicate a better repair effect. , In terms of the macrophage subtypes, the proportion of M2 macrophages in the Wnt3a group was significantly higher than that in the control group during the repair process. Also, the proportion of M2 macrophages was significantly higher in the regenerated bridging portion of the regenerated tissue than in the distal part, which may suggest a phenomenon that M2 macrophages determine the subsequent tissue regeneration.…”

“…61 A hedging immune strategy based microfibrous membrane (Him-MFM) has also shown promising results in scarless tendon healing. 11 However, additional basic research will be necessary to understand the optimal temporal and spatial presentation of macrophage involvement in tissue healing, and this will allow researchers to design better and more targeted biomaterials. In addition, the motor function of rats was also quantitatively evaluated.…”

“…Within 2–3 days following injury, the gene expression levels of proinflammatory cytokines at the injury site can increase several thousand-fold . Macrophages can differentiate into different subsets (proinflammatory M1 and anti-inflammatory M2 macrophages) with different biological functions in various environments and create a local inflammatory microenvironment together with other inflammatory signals. , In the early postinjury inflammatory microenvironment, rapid cascades of immune components will lead to cell death and matrix degradation and suppress tissue regeneration. ,, To achieve enhanced tendon healing and reduce the failure rate after tendon repair, modulating the shift from inflammatory to regenerative signaling during tendon regeneration could be a potential direction …”

“…6,9,10 To achieve enhanced tendon healing and reduce the failure rate after tendon repair, modulating the shift from inflammatory to regenerative signaling during tendon regeneration could be a potential direction. 11 Electrospinning, one of the most common methodologies in nanofiber production, involves applying a high voltage to a polymeric solution entrapped in a syringe to obtain biomimetic nanofibrous constructs. 12 These nanofibrous constructs can be used not only as tissue engineering scaffolds but also for a variety of applications such as delivery of bioactive molecules or drugs, electrical signaling, and antibacterial/microbial agents after appropriate modification and introduction of reactive substances.…”

Decellularized tilapia fish skin: A novel candidate for tendon tissue engineering

“…In clinical practice, the massive tendon defect can not be repaired by simply end-to-end suturing or using autografts due to the length or resource restriction, which commonly need the extra allografts or some biomaterials to handle this challenge. Currently, most of the commercially biological products are mammal-derived collagen products, like acellular small intestine submucosa (SIS), dermis, and pericardium [ 56 ]. However, just as we mentioned in introduction section, these mammal-derived decellularized ECMs have limitations such as limited donor sources, the potential risk of zoonotic diseases, and ethical and religious issues [ 20 ].…”