Platelet rich plasma and mechanical loading in regenerative tendon repair

Abstract Tendon injuries and tendinopathy are a growing problem in the aging but physically active population as well as athletes. Tendons have highly ordered matrix and undergo complex changes during the remodelling phase of tendon healing. Moreover, anaerobic metabolism and poor vascular network contribute to slow adaptation of tissue to the remodelled matrix which consequently results in slow and compromised healing. Such a destitute and slow healing process necessitates development of new and effective therapies and to combine therapies to obtain possibly synergistic effects. Addressing this clinical requirement, the work presented in this thesis investigates the role of two emerging treatment options, platelet rich plasma (pRP) and mechanical loading, on tendon healing. The effects of PRP, a rich autologous source of growth factors, on tendon cells was studied by modelling important stages of tendon healing in vitro. Key parameters such as cellular migration, chemotaxis, viability and senescence were investigated by means of different culturing and staining techniques together with microscopic analyses. PRP significantly increased migration and chemotaxis in human pnmary tenocyte culture. Moreover, PRP protected human tenocytes against challenging environments created by known tendon damaging drugs, dexamethasone and, ciprofloxacin, as well as the injury relevant condition of hypoxia. 11 Concurrently, an in vitro rat tail tendon injury model and static loading device was developed to assess the effect of static mechanical loading and PRP on the biochemical and biomechanical properties of tendon at the tissue level. This in vitro system was also used to investigate the synergistic effects of PRP and mechanical loading on tendon healing. Both PRP and mechanical loading helped to improve the biomechanical and biochemical properties of damaged tendon in vitro. In conclusion, the positive effects of PRP on key cellular parameters such as cell survival, migration and chemotaxis and also mechanical and biochemical properties of tendon tissue make it an important option for faster and less invasive tendon treatment. Additionally, an in vitro tendon injury model together with the mechanical loading device provide a new tool to investigate the mechanical boundary conditions suitable for treating different types of tendon disorders. The findings from the current study points towards the. significant contribution of PRP and mechanical loading to the healing process in tendons and could serve as a promising starting point for developing integrated therapeutic modalities to improve the quality and speed of recovery from tendon injury. 111.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Platelet rich plasma and mechanical loading in regenerative tendon repair

Tendon injuries and tendinopathy are a growing problem in the aging but physically active population as well as athletes. Tendons have highly ordered matrix and undergo complex changes during the remodelling phase of tendon healing. Moreover, anaerobic metabolism and poor vascular network contribute to slow adaptation of tissue to the remodelled matrix which consequently results in slow and compromised healing. Such a destitute and slow healing process necessitates development of new and effective therapies and to combine therapies to obtain possibly synergistic effects.Addressing this clinical requirement, the work presented in this thesis investigates the role of two emerging treatment options, platelet rich plasma (PRP) and mechanical loading, on tendon healing.The effects of PRP, a rich autologous source of growth factors, on tendon cells was studied by modelling important stages of tendon healing in vitro. Key parameters such as cellular migration, chemotaxis, viability and senescence were investigated by means of different culturing and staining techniques together with microscopic analyses.PRP significantly increased migration and chemotaxis in human primary tenocyte culture. Moreover, PRP protected human tenocytes against challenging environments created by known tendon damaging drugs, dexamethasone and ciprofloxacin, as well as the injury relevant condition of hypoxia.Concurrently, an in vitro rat tail tendon injury model and static loading device was developed to assess the effect of static mechanical loading and PRP on the biochemical and biomechanical properties of tendon at the tissue level. This in vitro system was also used to investigate the synergistic effects of PRP and mechanical loading on tendon healing. Both PRP and mechanical loading helped to improve the biomechanical and biochemical properties of damaged tendon in vitro.In conclusion, the positive effects of PRP on key cellular parameters such as cell survival, migration and chemotaxis and also mechanical and biochemical properties of tendon tissue make it an important option for faster and less invasive tendon treatment. Additionally, an in vitro tendon injury model together with the mechanical loading device provide a new tool to investigate the mechanical boundary conditions suitable for treating different types of tendon disorders.The findings from the current study points towards the significant contribution of PRP and mechanical loading to the healing process in tendons and could serve as a promising starting point for developing integrated therapeutic modalities to improve the quality and speed of recovery from tendon injury.</p

Platelet rich plasma and mechanical loading in regenerative tendon repair

Tendon injuries and tendinopathy are a growing problem in the aging but physically active population as well as athletes. Tendons have highly ordered matrix and undergo complex changes during the remodelling phase of tendon healing. Moreover, anaerobic metabolism and poor vascular network contribute to slow adaptation of tissue to the remodelled matrix which consequently results in slow and compromised healing. Such a destitute and slow healing process necessitates development of new and effective therapies and to combine therapies to obtain possibly synergistic effects.Addressing this clinical requirement, the work presented in this thesis investigates the role of two emerging treatment options, platelet rich plasma (PRP) and mechanical loading, on tendon healing.The effects of PRP, a rich autologous source of growth factors, on tendon cells was studied by modelling important stages of tendon healing in vitro. Key parameters such as cellular migration, chemotaxis, viability and senescence were investigated by means of different culturing and staining techniques together with microscopic analyses.PRP significantly increased migration and chemotaxis in human primary tenocyte culture. Moreover, PRP protected human tenocytes against challenging environments created by known tendon damaging drugs, dexamethasone and ciprofloxacin, as well as the injury relevant condition of hypoxia.Concurrently, an in vitro rat tail tendon injury model and static loading device was developed to assess the effect of static mechanical loading and PRP on the biochemical and biomechanical properties of tendon at the tissue level. This in vitro system was also used to investigate the synergistic effects of PRP and mechanical loading on tendon healing. Both PRP and mechanical loading helped to improve the biomechanical and biochemical properties of damaged tendon in vitro.In conclusion, the positive effects of PRP on key cellular parameters such as cell survival, migration and chemotaxis and also mechanical and biochemical properties of tendon tissue make it an important option for faster and less invasive tendon treatment. Additionally, an in vitro tendon injury model together with the mechanical loading device provide a new tool to investigate the mechanical boundary conditions suitable for treating different types of tendon disorders.The findings from the current study points towards the significant contribution of PRP and mechanical loading to the healing process in tendons and could serve as a promising starting point for developing integrated therapeutic modalities to improve the quality and speed of recovery from tendon injury.</p

Corrigendum to ‘A novel in vitro loading system for high frequency loading of cultured tendon fascicles’ [Med. Eng. Phys. 35 (2013) 205–210]

Tendon injuries are ubiquitous in the sporting and occupational environment. Clinically they present a challenge to Orthopaedic surgeons as they account for up to half of all sports injuries and almost half of reported work related ailments. The capacity for tendons to heal subsequent to injury is restricted due to their poor blood supply. Moreover, healed tendon tissue may be inferior to the intact tendon, having diminished biochemical and biomechanical properties and this brings about an ever increasing need for optimized treatment methods for tendon repair. Mechanobiology is concerned with how mechanical forces influence physiological and pathological aspects of the living tissue. However, the complex and poorly controlled loading environment in living organisms prevent the establishment of direct relationships between mechanical stimuli and tissue response. By developing a novel in vitro loading system (IVLS), the work in this thesis investigates the potential of a new and exciting biophysical loading intervention, High Frequency Low Magnitude (HFLM) mechanical loading, for stimulation of tendon repair and remodelling. Following a pre-defined stimulation period, healthy rat tail tendon fascicles (RTTFs) were evaluated for tissue viability and metabolism, Glycosaminoglycan (GAG) content, collagen arrangement and tangent modulus, using staining and biochemical assays, together with microscopy techniques, and mechanical testing. HFLM mechanically loaded tendons showed a trend for a higher tangent modulus than fresh tissue, and significantly higher modulus than unloaded. Further, when varying mechanical loading parameters of frequencies and dosages over clinically relevant ranges, a frequency dependent response was observed with increased tangent modulus and GAG content with increasing frequency. An association between high tendon crimp pattern and elevated tendon modulus as a result of HFLM mechanical loading was also demonstrated. Concomitantly, an injury model was developed to evaluate the effects of in vitro static, low frequency cyclic and HFLM mechanical loading conditions on the biochemical and biomechanical properties of in vitro damaged tendons. HFLM mechanically loaded damaged tendons again demonstrated significantly higher modulus and metabolism than unloaded tissue, although these were reduced below those of fresh damaged tissue. The findings in this thesis together with the newly developed IVLS reveal the potential for an exciting and unique biophysical therapeutic loading intervention for treatment of tendon injuries, and provide a scientific platform for further investigation of the effects of HFLM mechanical loads, potentially leading to an application within the clinic for enhanced connective tissue repair and remodelling.This thesis is not currently available in ORA