Efficacy of supraspinatus tendon repair using mesenchymal stem cells along with a collagen I scaffold

Abstract

ObjectivesOur main objective was to biologically improve rotator cuff healing in an elderly rat model using mesenchymal stem cells (MSCs) in combination with a collagen membrane and compared against other current techniques.MethodsA chronic rotator cuff tear injury model was developed by unilaterally detaching the supraspinatus (SP) tendons of Sprague-Dawley rats. At 1 month postinjury, the tears were repaired using one of the following techniques: (a) classical surgery using sutures (n = 12), (b) type I collagen membranes (n = 15), and (c) type I collagen membranes + 1 × 106 allogeneic MSCs (n = 14). Lesion restoration was evaluated at 1, 2, and 3 months postinjury based on biomechanical criteria. Continuous variables were described using mean and standard deviation (SD). To analyse the effect of the different surgical treatments in the repaired tendons’ biomechanical capabilities (maximum load, stiffness, and deformity), a two-way ANOVA model was used, introducing an interaction between such factor and time (1, 2, and 3 months postinjury).ResultsWith regard to maximum load, we observed an almost significant interaction between treatment and time (F = 2.62, df = 4, p = 0.053). When we analysed how this biomechanical capability changed with time for each treatment, we observed that repair with OrthADAPT and MSCs was associated with a significant increase in maximum load (p = 0.04) between months 1 and 3. On the other hand, when we compared the different treatments among themselves at different time points, we observed that the repair with OrthADAPT and MSCs has associated with a significant higher maximum load, when compared with the use of suture, but only at 3 months (p = 0.014). With regard to stiffness and deformity, no significant interaction was observed (F = 1.68, df = 4, p = 0.18; F = 0.40, df = 4, p = 0.81; respectively).ConclusionsThe implantation of MSCs along with a collagen I scaffold into surgically created tendon defects is safe and effective. MSCs improved the tendon’s maximum load over time, indicating that MSCs could help facilitate the dynamic process of tendon repair.

Biologics and stem cell‐based therapies for rotator cuff repair

“…Finally, immediate repair after laceration also does not mimic the clinical scenario in which tendon tears are usually left untreated for weeks or months prior to repair. To model delayed repair, a few groups recently carried out supraspinatus tendon detachment followed by surgical repair 3–16 weeks later . Prolonged unloading resulted in tendon retraction, muscle atrophy, fatty infiltration, and fibrotic scarring.…”

“…Differentiation can be carried out in vitro to create an engineered tendon/enthesis construct prior to implantation, or naive MSCs can be delivered within a biomimetic matrix to promote the proper cell fate in situ . Commonly used scaffolds for rotator cuff include electrospun fibers, xenograft tendon scaffolds, or hydrogels (typically fibrin or type I collagen gels) . The use of a carrier vehicle is advantageous since it ensures proper localization of delivered cells; the environment provided by the scaffolds has the additional potential to improve host cell proliferation or differentiation.…”

“…To model delayed repair, a few groups recently carried out supraspinatus tendon detachment followed by surgical repair 3-16 weeks later. 34,[42][43][44][45][46][47] Prolonged unloading resulted in tendon retraction, muscle atrophy, fatty infiltration, and fibrotic scarring. Despite eventual repair, these studies generally suggested that the pathological events associated with unloading cannot be reversed by simple reattachment.…”

“…[116][117][118][119] Commonly used scaffolds for rotator cuff include electrospun fibers, xenograft tendon scaffolds, or hydrogels (typically fibrin or type I collagen gels). 43,59,[120][121][122][123] The use of a carrier vehicle is advantageous since it ensures proper localization of delivered cells; the environment provided by the scaffolds has the additional potential to improve host cell proliferation or differentiation. While MSCs delivered within such carriers generally showed some positive indicators of improved healing (such as improved histology, fibrocartilage deposition, or expression of enthesis markers), 46,120,122 functional outcomes have been mixed.…”

The Holy Grail of Orthopedic Surgery: Mesenchymal Stem Cells—Their Current Uses and Potential Applications

“…At 4 and 8 weeks, SC migration improved maximum load to failure [100]. The use of ADMSCs, MDMSCs, and tenocyte-derived SCs has as well been analyzed in a rotator cuff model with promising results [101–103]. Furthermore, suturing a periosteal flap on top of the torn end of the infraspinatus tendon enhances tendon-to-bone healing in a rabbit rotator cuff model [104].…”