BMP‐12 gene transfer augmentation of lacerated tendon repair

The past, present and future in scaffold-based tendon treatments

“…Given there is currently no sufficiently effective pharmaceutical-based therapy, the use of more potent biological molecules was proposed as an alternative strategy. increases revascularisation of repairing tendon tissue, improving overall healing [169]; plateletderived growth factor (PDGF) has beneficial effects on the functional repair of tendon tissue in the canine model, increasing tendon glide, but not mechanical properties, over a 42 day period [170]; basic fibroblast growth factor (bFGF) stimulates both MSC proliferation and differentiation towards tenogenic lineage, leading to increased expression of tendon specific ECM proteins and increased collagen production from cells [171]; bone morphogenic protein 12 (BMP-12), also referred to as growth differentiation factor 7 (GDF-7) induces both in vitro and in vivo tenogenesis of MSCs in both human and equine cells [172][173][174]; BMP-13 (GDF-6) induces an increase in the expression of tendon specific proteins in rat MSCs along with increasing the characteristic wave like pattern found in tendon histological samples after 14 days implantation in a rat Achilles defect model [175]; BMP-14 (GDF-5) reduces adhesion formation between tendons and surrounding tissues, improving overall function and recovery [176]; early growth response protein 1 (EGR1) directs tendon differentiation in rat MSCs and improve tendon healing in a rat Achilles tendon injury model [177]; and transforming growth factor-β (TGF-β) is highly influential in the recruitment and maintenance of TC progenitor cells during injury [178]. While these growth factors have demonstrated efficacy, as assessed by increased cellular migration, matrix production and matrix mechanical properties over a short period of time (up to around 8 weeks), little difference has been documented in long term tissue integration, matrix composition and overall tissue strength over control groups [177,178].…”

The Basic Science of Tendinopathy

“…Depletion of Bgn and Fmod in mice leads to decreased expression of the tendon marker scleraxis (Scx) and of Type I collagen, and increased sensitivity to BMP2 in TSPCs when compared to cells from wild-type mice [18]. BMP12 acts as signaling molecules during embryonic tendon/ligament formation in animal experiments [67,112,114] and can stimulate patellar tendon fibroblasts proliferation in humans [40]. Expression of Scx, a member of the basic helix-loop-helix (bHLH) superfamily of transcription factors in the progenitors and cells of all tendon tissues [94], is crucial for differentiation of all force-transmitting and intermuscular tendons in Scx -/-mice [78] and for activation of the COL1a1 gene in mouse tendon fibroblasts in an in vitro study [63].…”

RETRACTED: Gene therapy and wound healing

“…Alternative to the in vitro gene transfer strategy several in vivo approaches have been investigated (67,70,72,80,81,108,(112)(113)(114)(115)\. One of the most practical methods to deliver the DNA to the skin is the direct injection of DNA.…”