S (approximately 80 to 100 nm in diameter), fibres (approximately 1.0 to 30 m in diameter) and fibre bundles (approximately 1,000 to 3,000 m in diameter), which ultimately form the tendon unit [94-98]. Although numerous material-based tendon PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/14960617 equivalents have been developed over the years, fibrous constructs (made through wet spinning [99-103], isoelectric focusing [104-106] or dry spinning [107-112] processes) lead the race in maintaining tendon cell phenotype, induction oftenogenic differentiation of progenitor cells, tendon regeneration and functional recovery in relevant in vivo models. This is attributable to the specific hierarchical order of the tendon unit. Indeed, such scaffold conformations provide topographical, spatial, chemical and immunological control over PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/744568 cells. They also provide mechanical stability/integrity for large tendon defects and a template for the organisation of the neotendon tissue. Although dry spinning has been shown to denature the triple-helical conformation of natural biopolymers [113,114], it has been extensively used, with profound success, as a stem cell carrier with synthetic polymers. In a large rotator cuff rabbit model, electro-spun polyglycolic acid fibres loaded with autologous BMSCs exhibited not only a higher type I to type III collagen ratio, but also significantly improved tensile strength compared to the control groups at 16 weeks post-implantation [115]. A knitted polylactide-co-glycolide micro-fibrous construct loaded with allogeneic rabbit BMSCs and implanted in a rabbit Achilles tendon model demonstrated similar histological results to the construct alone and native tendon repair. However, the tensile stiffness of BMSC-seeded constructs was only 87.0 of that of the normal tendon and the modulus was only 62.6 of that of the normal tendon [116]. To further enhance stem cell retention on fibrous materials, composite implantable devices based on a hydrogel stem cell carrier and a fibrous load-bearing structure have been assessed. In a rabbit Achilles tendon repair model, pre-tensioned polyglyconate sutures loaded with autologous rabbit BMSCs in contracted collagen gel demonstrated significantly improved cellular organisation, extracellular matrix organisation and biomechanics [117]. In a patellar tendon repair model, polyglyconate sutures loaded with autologous rabbit BMSCs in contracted collagen gel demonstrated significantly higher mechanical properties than the naturally repaired counterparts, whilst no significant differences in cellular organisation or 2-Chloro-3-methoxyaniline histological appearance were observed between the groups at 12 and 26 weeks post-surgery [118]. Electro-spun polylactide-co-glycolide scaffolds, loaded with heparin/fibrin hydrogel, ADSCs and platelet derived growth factor BB demonstrated improved tendon healing in a dog model of transected flexor digitorum profundus tendons [119]. Collectively, these studies show that aligned fibrous scaffolds that closely imitate the architecture of tendon tissue offer structural and mechanical N-BOC-3-Fluoro-D-phenylalanine benefits, along with an instructive physical environment that guides new functional tissue development. However, such carriers alone are insufficient for complete ijms17122034 recapitulation of tendon function. Functionalisation with a hydrogel that would enable localisation/retention of seeded cells and spatiotemporal release of vital biomolecules would further improve clinical outcomes.Abbah et al. Stem Cell Research Therapy 2014, 5:38 http://stemcellres.com/content/5.