Rotator Cuff Repair Augmentation Using Osteoinductive Growth Factors

Abstract

Rotator cuff injuries (RCIs) present a major health problem due to high incidences of degenerative tears greater than 3 cm and prevalence of re-tears following surgical procedures. Since healing and functional restoration relies upon bone ingrowth into the tendon, it is hypothesised that sustained delivery of osteoinductive factors including bone morphogenetic proteins (BMPs), specifically BMP2-7, may significantly improve RCI tendon-bone healing. Here, growth factor candidates and delivery mechanisms are reviewed, specifically for improved RCI healing through enhanced bone ingrowth. In addition to BMPs, other potentially osteogenic factors including platelet-derived growth factors (PDGF), fibroblast growth factor (FGF), transforming growth beta isoforms (TGF-β1 and TGF-3) and parathyroid hormone (PTH) are evaluated since they can induce bone formation at the healing tendon attachment site. Several challenges must be addressed prior to clinical translation. The majority of published studies utilise in vivo animal models. In general, BMP-7 demonstrates a stronger stimulating effect when compared to BMP-2; the reported effectiveness of BMP-2 is often conflicting. Alternative factors, including PDGF and PTH, also demonstrate potential for assisting bone growth in enthesis healing. The use of sustained and biomimetic delivery systems appears to have the greatest positive effects. Some studies have demonstrated a dose-dependent effect, in conjunction with varying age, indicating that stratified therapies could be a viable solution for RCI healing. To adequately resolve potential treatments for RCI, further expanded and correlated animal trials must be undertaken, and indicative human trials are required with consideration of surgical and patient-specific influences.

Visualizing the Fate of Intra‐Articular Injected Mesenchymal Stem Cells In Vivo in the Second Near‐Infrared Window for the Effective Treatment of Supraspinatus Tendon Tears

“…[62] During the repair stage, numerous growth factors are expressed, including transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP), which are essential for cell differentiation into a chondrocyte phenotype in the repair stage of enthesis healing. [63][64][65][66] Therefore, it is reasonable to postulate that the greater the number of MSCs and the longer residence time retained in the footprint during the repair process are, the more MSCs that differentiate and integrate into the repaired tissue. Quantitative analysis further revealed that the area under the curve (AUC) in the moderate density group was 2.4-fold higher than that of the high density group and 16.4-fold higher than that of the low density group (P < 0.05, Figure 4e) during the repair stage.…”

“…It is worth noting that the enthesis healing undergoes 3 stages: inflammation (0–7 days), repair (5–14 days) and remodeling (>14 days) . During the repair stage, numerous growth factors are expressed, including transforming growth factor‐β (TGF‐β) and bone morphogenetic protein (BMP), which are essential for cell differentiation into a chondrocyte phenotype in the repair stage of enthesis healing . Therefore, it is reasonable to postulate that the greater the number of MSCs and the longer residence time retained in the footprint during the repair process are, the more MSCs that differentiate and integrate into the repaired tissue.…”

“…Osteogenic and Adipogenic Differentiation of Tat-PbS QDs Labeled MSCs: The differentiation medium was prepared as described in the previous study. [66] For osteogenic differentiation, MSCs labeled with different concentration of Tat-PbS QDs (0, 10, 20, and 30 µg mL −1 ) were cultured in a α-MEM and 10% FBS medium containing dexamethasone (10 −7 m), β-glycerol phosphate (10 × 10 −3 m) and ascorbate-2phosphate (50 × 10 −6 m). Osteogenic cells were determined by ALP staining and von Kossa staining at 14 and 28 days after induction, respectively.…”

The Use of Platelet-Rich Plasma (PRP) for the Management of Non-union Fractures

“…The use of PRP in tissue regeneration is a rapidly evolving area for both clinicians and researchers and is being employed in various fields, including osteoarthritis [9], rotator cuff repair [10,11] and bone regeneration [12]. This is because autologous platelet concentrations offer an easy, cost-effective method to obtain the high concentrations of specific growth factors Inadequate immobilisation, yet adequate blood supply.…”

TGF–β3 Loaded Electrospun Polycaprolacton Fibre Scaffolds for Rotator Cuff Tear Repair: An in Vivo Study in Rats

“…Promising candidates for such grafts are electrospun fibre scaffolds consisting of polycaprolactone (PCL; [19,20]. These scaffolds consist of spatially oriented fibres with a very high surface area which is a prerequisite for the possible binding of biologically active molecules and the binding of cells [21,22]. PCL is biodegradable with slow degradation rates in vivo [23,24] and PCL-based materials for medical devices such as Capronor, a subdermal implant for long-term drug delivery [25] or drug delivery systems for glaucoma treatment [26] are already in clinical use or trial.…”