Project: Regenerative Medicine Products for the Treatment of Skin and Cartilage Lesions
Since its beginning, tissue engineering focused on the identification of sources of cells with increased differentiation capacity to be explanted from the patient, expanded “in vitro” and re-administered to the same patient as a cell suspension or in association with a suitable biomaterial. Despite the remarkable progress made during the last two decades, the “in vitro” fabrication of substitutes for tissues has not reached the stage of routine clinical applications yet. Indeed, the use of “ex vivo” tissue engineered constructs is highly limited because of economic and regulation-related issues, which confine this approach only to extreme life or organ saving situations. _x000D_The rapidly developing knowledge about the pathways activated during the healing process and the new information about the natural response of the body to injury suggest that the recipient organism itself could provide key elements necessary for tissue repair, thus suggesting a novel therapeutic approach based on the activation of the endogenous regenerative capacity of the tissue. The new strategy aims at the stimulation of the intrinsic endogenous potential of a tissue to heal or regenerate by using “off the shelf” standardized products without cells. Novel biomaterials are being designed that, by mimicking the tissue wound microenvironment, promote tissue development and regeneration “in vivo”. The use of minimally invasive procedures qualifies the endogenous regeneration strategy for a broader application. _x000D__x000D_Although every tissue has a specific response to healing, there is a general pattern of resolution shared by most tissues. The initial stage after damage is characterized by hematoma and clot formation. During soft or hard tissue healing, blood platelets are the CO source of released growth factors that are the initial triggers of the process. Upon vessel injury, the platelets form a plug that stabilizes the clot within the fibrin meshwork. Platelets are activated by the thrombin and release their polypeptides content crucial for signaling the immune cells migration. Immune cells and their secreted factors are crucial for the progression of the physiologic response to the injury. The immune cells, theirs secreted factors, and the hematoma creates, at the site of the wound, an inflammatory microenvironment which then brings about the recruitment of local mesenchymal and epidermal cells migration, _x000D_Critical skin and articular cartilage lesions and deficits, caused by disease and trauma, do not spontaneously heal and require regenerative therapies to be successfully repaired. The introduction of the autologous platelet concentrate - the Platelets Rich Plasma (PRP) - into the clinical practice as tissue healing stimulator was suggested by Marx and coworkers in 1998. In addition of being autologous in nature and therefore without risks of disease transmission or immunogenic reaction, the PRP offers the advantage of being the concentrate of the ‘right’ factors in the ‘right’ proportions necessary for the healing process. _x000D__x000D_Autologous PRP has been proposed by clinicians for the treatment of chronic skin ulcers. The PRP was found not only to improve vascularization by increasing endothelial cells recruitment, migration and organization with a potential to increase mRNA expression of VEGF and PDGF, but also to enhance the whole skin regeneration by promoting recruitment and proliferation of circulating and/or locally resident mesenchymal and epithelial stem/ progenitor cells, their division and their synthesis of macromolecules of the extracellular matrix. _x000D_Interestingly, the use of PRP has been proposed in the orthopedic field also for the treatment of a tissue characterized by the lack of vascularization such as the articular cartilage. We have published that freshly prepared autologous PRP associated to a suitable biomaterial favored healing of full thickness cartilage lesions in a prospective case series of 52 patients (Siclari et al. 2012). Compared with the time before surgery, at 12 months postoperatively, all patients showed improvements in daily living activities, sports and recreation functions, and knee-related quality of life as assessed by the Knee Osteoarthritis Outcome Score (KOOS). _x000D__x000D_In this project, we generated a Pship of industries and globally recognized experts that collectively (expertise and resource) will develop and validate two innovative products for the treatment of critical skin and cartilage lesions and defects by having the following specific objectives:_x000D_- establish protocols for the production of an allogenic, non immunogenic platelet derived, growth factor rich component _x000D_- develop and industrialize innovative bio-active biomaterials containing human platelet derived products and acting through a regenerative medicine approach_x000D_- validate these biomaterials by in vitro studies and by their pre-clinical testing in animal models_x000D_- launch two human clinical studies (proof of principle).
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Acronym
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Re.Me.Pro
(Reference Number: 8119)
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Duration
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05/02/2014 - 31/01/2017
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Project Topic
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Combining biomaterials and platelet derived components, develop and validate marketable “off the shelf” products: a) an active biomembrane for the repair of skin lesions such as chronic ulcers, difficult wounds, bedsores; b) an active scaffold for the repair of cartilage lesions and defects
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Network
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Eurostars
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Call
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Eurostars Cut-Off 10
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Project partner
