With the development in radiotherapy techniques there has been reduction in side effects compared to the treatment outcomes of some several decades ago. In this same regard, success rates for curative treatments are generally increasing, presenting increased demand for improved radiation cosmesis (i. e. reduction in side effects). This is no less true for those treated for lymphoma, taken together with the associated risks of cardiovascular disease. The extracellular matrix (ECM) is a complex medium comprising the non-cellular functional components that surrounds cells. The ECM is composed mainly of fibrous proteins such as collagen and a gel of carbohydrate polymers called glycosaminoglycans (GAG). The ECM provides a range of vital roles including mechanical support, cell signalling and water and solutes transportation, each potentially modified as a result of irradiation. The aim of this study has been to investigate the effect of penetrating photon irradiation on the biophysical and infrastructural properties of extracellular matrix (ECM) macromolecules. Hyaluronan (HA) molecules and collagen fibres were chosen because of their crucial mediating roles in controlling the physiological functions of the ECM. The present work was guided by doses that can be delivered to the synovial joint and pericardium as a result radiotherapy. In respect of biophysical characterisation, numbers of measurements were conducted for HA solutions, this being the main component of the synovial fluid. Different concentrations in the range (0. 01-1% w/v) were studied. These measurements included viscosity, pH, ultraviolet irradiation (UV), Gel Permeation Chromatography (GPC) (for molecular weight characterisation) and Raman microspectrometry. Mechanical testing, with results controlled by the various structural elements, were performed on pericardium, uniaxial testing and atomic force microscopy (AFM) being used