| Rotator cuff tear is among the most common soft tissue injuries that occurs in middle and older age, leading to debilitating pain, reduced shoulder function, and weakness. Despite advancements in surgical repair techniques, rotator cuff repairs experience a high rate of failure because of fibrous scar tissue regeneration with obvious inferior biomechanical characters. Osteoporosis, tendons degeneration, severe tendon weakening, muscle atrophy, and size of the original defect are considered important risk factors for retear. New repair strategies are required that can not only provide effective mechanical reinforcement of RC repair but also stimulate and enhance the patients’ intrinsic healing potential. The application of scaffolds to promote tissue regeneration at the tendon-bone insertion site has gained increasing interest.Objective 1. To evaluate the extent to which augmentation of chronic RCTs repairs with b FGF-loaded electrospun PLGA fibrous scaffolds would improve functional and biomechanical outcomes in a rat model. 2. To evaluate the extent to which augmentation of chronic RCTs repairs with CPS ceramic would improve the functional and biomechanical outcomes in a rat model. 3. To demonstrate the feasibility of fabricating electrospun scaffolds consisting of two differently scaled fibers interspersed evenly throughout an entire construct, to fabricate scaffolds containing PCL and CS fibers, and to evaluate the extent to which augmentation of chronic RCTs can be repaired.Methods 1. Emulsion electrospinning was adopted to prepare b FGF-loaded PLGA electrospun fibrous membranes with a core-sheath structure. The b FGF-PLGA fibrous scaffolds were then characterized and evaluated by in vitro and in vivo results of cell proliferation and repairs of RCTs. 2. Chronic RCT models were built and augmented with CPS bioceramics. At 2, 4, or 8 weeks postoperatively, microcomputed tomography was utilized to quantify the new bone formation at the repair site. New fibrocartilage formation and collagen organization at the tendon-bone interface was evaluated by histomorphometric analysis. Biomechanical testing of the supraspinatus tendon-bone complex was performed. 3. The multi-scale electrospun PCL-CS fibrous scaffolds were characterized and evaluated by in vitro and in vivo results of cell proliferation and repair outcomes of chronic RCTs.Results 1. Emulsion electrospinning fabricated ultrafine fibers with a core-sheath structure which secured the bioactivity of b FGF in a sustained manner for three weeks. Histological observations showed that electrospun fibrous scaffolds have excellent biocompatibility and biodegradability. At 2, 4 and 8 weeks after in vivo RCT repair surgery, electrospun fibrous scaffolds significantly increased the area of glycosaminoglycan staining at the tendon-bone interface compared with the control group, and b FGF-PLGA significantly improved collagen organization compared with the control and PLGA groups. Biomechanical testing showed that the electrospun fibrous scaffolds groups had a greater ultimate load to failure and stiffness than the control group at 4 and 8 weeks. The b FGF-PLGA scaffolds had the highest ultimate load to failure, stiffness and stress of the healing enthesis, and the superiority compared to PLGA alone was significant. 2. Microcomputed tomography analysis demonstrated remarkable osteogenic activity and osteoconductivity to promote new bone formation and ingrowth of CPS bioceramic. Histological observations indicated that CPS bioceramic had excellent biocompatibility and biodegradability. At early time points after the RC repair, CPS bioceramic significantly increased the area of fibrocartilage at the tendon-bone interface compared with the control and HA groups. Moreover, CPS and HA bioceramics had significantly improved collagen organization. Biomechanical tests indicated that the CPS and HA groups have greater ultimate load to failure and stiffness than the control group at 4 and 8 weeks, and the CPS specimens exhibited the maximum ultimate load to failure, stiffness, and stress of the healing enthesis. 3. Multi-scale fibrous scaffolds comprised of microfibers of PCL and nanofibers of CS were successfully fabricated using a dual electrospinning process. SEM results indicated that the electrospun fibrous scaffolds consisted of multi-scale fibers of 1.16±0.27 μm PCL and 0.36±0.23 μm CS. Multi-scale fibrous scaffolds were moderately hydrophilic at 40.3° water contact angle, had high water absorption and accelerated degradation time, with a tensile strength of 2.71±0.36 MPa. In vitro results demonstrated that multi-scale fibrous scaffold could significantly promoted fibroblast cell growth and proliferation than PCL fibers alone. Microcomputed tomography analysis revealed that multi-scale fibers promoted new bone formation and ingrowth. Histological observations demonstrated that the electrospun fibrous scaffolds have excellent biocompatibility and biodegradability. Multi-scale fibrous scaffolds had significantly improved collagen organization based on birefringence under polarized light at the healing enthesis compared with the control group, and significantly increased the area of glycosaminoglycan staining at the tendon-bone interface compared with the control and PCL group. Biomechanical tests showed that PCL groups have greater ultimate load to failure and stiffness than the control group at 4 and 8 weeks, and multi-scale scaffolds have maximum ultimate load to failure, stiffness and stress of the healing enthesis.Conclusion 1. Electrospun b FGF-PLGA fibrous scaffolds aid in cell attachment and proliferation,as well as accelerating tendon-bone remodeling, and b FGF-loaded PLGA fibrous scaffolds have a more pronounced effect on tendon-bone healing. 2. Calcium phosphate-based bioceramics aid in cell attachment and proliferation and accelerate new bone formation, and CPS bioceramic has a more prominent effect on tendon-to-bone healing. 3. Electrospun fibrous scaffolds help aid in cell attachment and proliferation, as well as to accelerate tendon-bone remodeling, and multi-scale fibrous scaffolds have a more pronounced effect on tendon-bone healing. Multi-scale fibrous scaffolds are a promising treatment for RCT. |
PDF Full Text Request