Temporary Hierarchical Scaffold Structure for Tendon Regeneration

Temporary Hierarchical Scaffold Structure for Tendon RegenerationLucy Bosworth*, Sandra DownesSchool of Materials, The University of Manchester, Grosvenor Street, Manchester, M1 7HS, [email protected] IntroductionMorbidity related tendon injuries pose a personal and clinical burden, which has not been met by available treatments. The rate of degeneration and spontaneous rupture of tendon tissue is increasing; mostly due to population aging and increased uptake of sporting and other recreational activities [1]. Current interventions often have a poor outcome, resulting in loss of function, further degeneration and rupture [2,3]. Autografts and allografts can cause additional morbidity and tissue rejection respectively [4]. We have created a scaffold that closely replicates the structural and physical properties of tendons as a potential resolution to tendon injury [5]. In natural tissue, tendon is an organised structure with aligned collagen type I fibres lying parallel to the tendon axis [6]. The hierarchical configuration is formed by a collection of these fibres into bundles, which in-turn are grouped forming the overall tendon structure. Tenocytes are located amongst these fibres in a columnar array and are responsible for ECM production [7]. The adaptability of the electrospinning process, which allows the use of a variety of biomaterials and control of fibre diameter, justifies its use in regenerative medicine applications for creating scaffolds capable of mimicking the structural properties of the tissue they are intended to restore. We have developed a 3D scaffold appropriate for surgical implantation into damaged tendons. It is envisaged that this synthetic structure will perform the mechanical functions of a tendon whilst, promoting cell migration and subsequent repair. The biodegradable properties of the polymer, in this case polycaprolactone, will allow scaffold degradation at the same rate as new tissue forms, allowing a smooth transfer of load and avoiding further invasive surgery with its associated risk of infection and recovery time. It is hypothesised that implantation of this tendon scaffold will facilitate appropriate tendon healing, leading to improved clinical outcomes for sufferers of tendon pathology. Here we report data demonstrating a new hierarchical 3D scaffold for tendon regeneration. Materials and MethodsPolymer solution properties: concentration 10%w/v (PCL/acetone), PCL Mw 80,000. Electrospinning parameters: 20kV, 0.01ml/min and tip to collector 15cm. The target collector was a fine edged rotating mandrel. Post-electrospinning, the mat of highly aligned PCL fibres was removed, submerged in distilled water and then twisted together. Subsequent fibre bundles were either plaited or twisted together to further assemble the hierarchical structure aimed for. Biocompatibility testing and gene expression studies of seeded tenocytes on these fibrous bundles were performed.Results and DiscussionThe fibrous bundles (??189.83 ?? 15.84??m) are each composed of hundreds of nanofibres (??0.36 ?? 0.11??m) and appear to demonstrate ???contact guidance??? for directing cell orientation . Depending on the level of tendon damage sustained, bundles can be further grouped to replicate the natural hierarchical structure. Mechanical data of individual bundles demonstrated a Modulus of 5.27 (??2.03) MPa and tensile strength 2.17 (??0.58) MPa; plaited bundles yielded a Modulus of 14.01 (??3.42) MPa and tensile strength 6.36 (??1.82) MPa.ConclusionWe have developed 3D structures containing aligned nanofibres, which mimic the original tendon tissue, aid cellular orientation and are biocompatible. Depending on the extent of tissue damage, we are able to add to this construct without impeding mechanical properties. References[1] Smith, R.K.W., Birch, H.L., Goodman, S., Heinegard, D., Goodship, A.E. Comparative Biochemistry and Physiology Part A 133 (2002) 1039???1050[2] Miedema HS, van der Linden SM, Rasker JJ, Valkenburg HA. Rheumatology 1998;37(5):555-561[3] Maffulli N, Sharma P, Luscombe KL. J R Soc Med 2004;97(10):472-476[4] Sahoo et al[5] Bosworth et al[6]Sharma P, Maffulli N. The Surgeon, 2005, Vol 3, No5[7] Kidoaki S, Kuen Kwon I, Matsuda T. Biomaterials 26 (2005) 37-46