Table 1.
Summary of key pre-clinical studies using growth factor delivery to augment rotator cuff repair
| Growth Factor | Dose | Delivery Scaffold | Loading Method | Duration of Release | Animal Model | Scaffold Placement | Histological and Biomechanical Outcome | Reference |
|---|---|---|---|---|---|---|---|---|
| 75, 150, 500 μg | Type I collagen matrix | Soaking | Sheep infraspinatus tendon detachment and acute repair | Interpositional to the repaired infraspinatus tendon-to-bone insertion | Better tendon-to-bone interdigitation and higher ultimate load-to-failure in the 75 μg and 150 μg PDGF-BB with type I collagen matrix group than the 500 μg group and suture only control at 12 weeks. Higher doses led to poor morphological appearance and biomechanics. | (Hee et al., 2011) | ||
| 0.5 μg | Gelatin hydrogel sheets | Soaking | 100% released within 2 weeks during subcutaneous implantation | Rat supraspinatus tendon detachment and acute repair | Lateral to the repaired supraspinatus tendon-to-bone insertion | Better organized collagen fiber at the insertion site and significantly greater ultimate load-to-failure and stiffness in the PDGF-BB treated group than that in the suture repair and PBS-soaked gelatin hydrogel sheet controls at 12 weeks. | (Tokunaga et al.,2015a) | |
| 0.6, 2, 6 μg | Type I collagen scaffold | Soaking | Rat supraspinatus tendon detachment and acute repair | Bursal to the repaired supraspinatus tendon-to-bone insertion | Dose-dependent response in cellular proliferation and angiogenesis in PDGF-BB delivery group at 5 days compared with repair only and scaffold only control. No significant difference between treatment and control groups on the area of fibrocartilage, collagen fiber orientation, or biomechanical properties at 28 days. | (Kovacevic et al., 2015) | ||
| 896 ng/cm | Fiberwire sutures | Dip coating | 80% released within 1 hour, and remaining released in 48 hours | Sheep infraspinatus tendon detachment and chronic repair | Significantly better organized gap tissue with extensive cartilage formation at the tendon-to-bone interface in the rhPDGF-BB coated sutures repair group compared with controls at 6 weeks, but ultimate load-to-failure was equivalent to uncoated controls. | (Uggen et al., 2010) | ||
| 0.5, 5 and 50 μg | Gelatin hydrogel sheet | Soaking | 100% released within 2 weeks | Rat supraspinatus tendon detachment and acute repair | Interpositional to the repaired infraspinatus tendon-to-bone insertion | Significant improvement in mechanical strength in the FGF-2-treated group at 6 and 12 weeks. No significant difference between different doses. | (Tokunaga et al.,2015b) | |
| 2 μg | Electrospun PLGA fibrous membrane | Emulsion encapsulation | 50% released in 2 weeks in a sustained manner | Rat supraspinatus tendon detachment and chronic repair | Bursal to the repaired supraspinatus tendon-to-bone insertion | Significantly improved collagen organization and highest ultimate load-to-failure and stiffness in the bFGF–PLGA scaffolds than control suture repair and PLGA scaffold alone groups at 8 weeks. | (Zhao et al., 2014) | |
| 3, 30 μg | Gelatin hydrogel sheet | Dip coating | 30% released within 1 day and the remaining released in a sustained manner in approximately 2 weeks | Rabbit supraspinatus tendon detachment and acute repair | Placed in a created bony trough interpositional to the repaired infraspinatus tendon-to-bone insertion | Histologically and biomechanically enhanced rotator cuff tendon-to-bone healing in both 3 and 30 μg of FGF-2 impregnated gelatin hydrogel sheets with no significant difference between the two doses at 6 weeks. | (Tokunaga et al.,2017) | |
| F2A (peptide mimetic of FGF-2) | 1, 8 mg | Collagen-coated P4HB fibrous scaffold | Dripping | Sheep infraspinatus tendon detachment and acute repair | Bursal to the repaired infraspinatus tendon-to-bone insertion | The extent of delamination decreased with increasing doses of F2A, and more tendon-like tissue and new bone formation was observed in the growth factor augmented group at 8 weeks. | (Peterson et al.,2015) | |
| 50 μg/ml | Acellular dermal patch | Coated on the surfaces and then freeze dried | 75% released in a sustained manner in 2 weeks | Rabbit supraspinatus tendon detachment and chronic repair | Interpositional to the repaired supraspinatus tendon-to-bone insertion | Greater new bone formation, cell penetration into the host bone, well connected interface with no gap formation, and significantly higher ultimate tensile load in the rhBMP-2 augmented repair group at 8 weeks. | (Lee et al., 2017) | |
| 0.5 μg | Gelatin hydrogel sheet | Coated on the gelatin hydrogel sheets | 90% released in a sustained manner within 2 weeks | Rat supraspinatus tendon detachment and acute repair | Bursal to the repaired supraspinatus tendon-to-bone insertion | Significantly higher tendon maturing score and highest ultimate load-to-failure in the BMP-7 delivery from gelatin hydrogel sheet group than the following controls: direct injection of BMP-7, gelatin hydrogel sheet alone, and the suture repair alone, respectively, at 8 weeks. | (Kabuto et al., 2015) | |
| BMP-12 | ||||||||
| 75*/30† μg | Type I/III collagen sponge | † Bursal to the repaired supraspinatus tendon-to-bone insertion | ||||||
| TGF-β3 | 2.75 μg | Calcium phosphate matrix | Injected into the calcium phosphate matrix | Rat supraspinatus tendon detachment and acute repair | Placed in a created bony trough interpositional to the repaired infraspinatus tendon-to-bone insertion | Improved fibrocartilage formation and collagen organization at the enthesis in the calcium phosphate matrix alone group than the calcium phosphate matrix with TGF-β3 at 2 weeks. | (Kovacevic et al., 2011) | |
| TGF-β1 | 0.1 μg | Gelatin hydrogel sheet | Soaking | Rat supraspinatus tendon detachment and acute repair | Interpositional to the repaired supraspinatus tendon-to-bone insertion | Tough fibrous tissues at the healing site with significantly higher ultimate load-to-failure and higher collagen content in the TGF-β1 gelatin hydrogel sheets group than saline control at 12 weeks. | (Arimura et al.,2017)) |