Abstract
The potential of multifunctional wound heal biomaterial relies on the optimal content of therapeutic constituents as well as the desirable physical, chemical, and biological properties to accelerate the healing process. Formulating biomaterials such as amnion or collagen based scaffolds with natural products offer an affordable strategy to develop dressing material with high efficiency in healing wounds. Using image based phenotyping and quantification, we screened natural product derived bioactive compounds for modulators of types I and III collagen production from human foreskin derived fibroblast cells. The identified hit was then formulated with amnion to develop a biomaterial, and its biophysical properties, in vitro and in vivo effects were characterized. In addition, we performed functional profiling analyses by PCR array to understand the effect of individual components of these materials on various genes such as inflammatory mediators including chemokines and cytokines, growth factors, fibroblast stimulating markers for collagen secretion, matrix metalloproteinases, etc., associated with wound healing. FACS based cell cycle analyses were carried out to evaluate the potential of biomaterials for induction of proliferation of fibroblasts. Western blot analyses was done to examine the effect of biomaterial on collagen synthesis by cells and compared to cells grown in the presence of growth factors. This work demonstrated an uncomplicated way of identifying components that synergistically promote healing. Besides, we demonstrated that modulating local wound environment using biomaterials with bioactive compounds could enhance healing. This study finds that the developed biomaterials offer immense scope for healing wounds by means of their skin regenerative features such as anti-inflammatory, fibroblast stimulation for collagen secretion as well as inhibition of enzymes and markers impeding the healing, hydrodynamic properties complemented with other features including non-toxicity, biocompatibility, and safety.
Highlights
Amnion or its major component, collagen proteins, offer an affordable source to develop biomaterials for various therapeutic purposes as the non-immunogenic membrane represents an advantageous source of progenitor cells, tissue regenerative growth factors and substances, and various types of collagen (Ilic et al, 2016)
Collagen types I and III are the major components of the skin (Lovell et al, 1987) and during wound healing, it is typically produced by the fibroblast cells moving into the wound site (Rittie, 2016)
kappa carrageenan (KC) could be a good component that can be combined with amnion to modulate local wound environment
Summary
Amnion or its major component, collagen proteins, offer an affordable source to develop biomaterials for various therapeutic purposes as the non-immunogenic membrane represents an advantageous source of progenitor cells, tissue regenerative growth factors and substances, and various types of collagen (Ilic et al, 2016). Local wound environment in chronic conditions is characterized by the presence of excess exudates with elevated protease activity, defective extracellular matrix (ECM) and failure of epithelialization and vascularisation that produce systemic effects on the physiology (Harding et al, 2002) These effects stimulate the production of chemokines resulting in elevated levels of inflammatory cells in the wound environment to delay healing. Other clinical impediments such as diabetes, hypertension, other ailments, infections and patient’s health status are the factors that contribute to delay in healing (Harding et al, 2002) These studies indicate that both local wound environment and systemic effects should be sought in case of impaired healing (Reinar et al, 2008). Instead of direct therapeutic intervention, biomaterial based gradual alteration to wound site allows individuals physiology to participate in healing
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