Biorigen Srl.

Genova, Italy

Biorigen Srl.

Genova, Italy

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El Backly R.M.,University of Genoa | El Backly R.M.,Instituto Nazionale per la Ricerca sul Cancro | El Backly R.M.,Alexandria University | Zaky S.H.,University of Genoa | And 14 more authors.
Tissue Engineering - Part A | Year: 2013

The periosteum plays a pivotal role during bone development and repair contributing to bone vascularization and osteoprogenitor cells source. We propose a periosteal substitute engineered using a platelet-rich plasma (PRP) membrane incorporating autologous bone marrow-derived mesenchymal stem cells (PRP/BMSC gel membrane) to be wrapped around an osteoconductive scaffold for regeneration of compromised bone defects. The PRP/BMSC gel membrane was optimized using different compositions for optimal release of vascular endothelial growth factor (VEGF) and platelet derived growth factor-BB (PDGF-BB). Survival and proliferation of cells in the PRP gel membrane with time were confirmed in addition to their osteogenic capacity. Furthermore, to evaluate the possible effects of the PRP/BMSC gel membrane on surrounding progenitor cells in the injury area, we found that the PRP gel membrane products could significantly induce the migration of human endothelial cells in vitro, and increased the expression of bone morphogenetic protein 2 in cultured BMSC. These cells also secreted significant amounts of soluble proangiogenic factors, such as PDGF-BB, VEGF, and interleukin-8 (IL-8). Finally, the functionality of the PRP/BMSC gel membrane periosteal substitute for bone regeneration was tested in vivo both in an ectopic mouse model as well as in a rabbit segmental bone defect model providing evidence of its capacity to biomimic a periosteal response enhancing bone regeneration. © Mary Ann Liebert, Inc.


Patent
Biorigen S.r.l, Lorandi, Motta and Migliaresi | Date: 2013-04-03

The invention describes a freeze-dried compound composed of a polymeric matrix containing platelet rich plasma (PRP) and/or platelet lysate (PL) and/or platelet poor plasma (PPP) and/or cryoprecipitate (CRYO), and/or platelet membrane rich plasma (PMRP) which have a suitably long shelf-life and possesses, at the same time, improved characteristics of polymeric matrix re-absorption and in vivo efficacy. The freeze-dried compound can be stored in standard ways for a suitably long period of time and be reconstituted just before the use by mean of a simple water absorption in a relatively short period of time. The reconstituted hydrogel shows physical and mechanical properties compared to those of the starting hydrogel with PRP before freeze-drying..


Patent
Biorigen S.r.l, Lorandi, Motta and Migliaresi | Date: 2013-04-03

The invention regards the use of gelatin hydrogels that are solid at room temperature and melt or present a gel-sol transition at temperatures near the body temperature, so assuming a liquid state when put contact with body, implanted in the body or heated at temperatures compatible with the body. The gelatin-based hydrogels may contain biologically active agents and/or cells that after hydrogel melting or gel-sol transition, are fast released in situ, thus explicating the therapeutic and biological action. The gelatin-based hydrogels, containing or not containing biologically active agents, may be solid at the temperature of the skin (33C) and melt when water or aqueous solution at a temperature compatible to the body is poured onto for an easy removal of the hydrogels.


Scala M.,Italian National Cancer Institute | Gipponi M.,St Martino Hospital | Mereu P.,Italian National Cancer Institute | Strada P.,St Martino Hospital | And 7 more authors.
In Vivo | Year: 2010

Osteoradionecrosis (ORN) of the mandible is a major complication of radiation therapy of head and neck cancer with a potential of occurrence ranging from 5 to 15% of the irradiated patients. Due to the gradual necrotic process, the mandibular bone becomes necrotic and looses its spontaneous regeneration ability. Containing an elevated content of mitogenic and osteogenic growth factors, the use of platelet rich plasma (PRP) from autologous source has been suggested to re-activate the healing process of osteogenesis. Autologous PRP gel was introduced into the ORN necrotic defect of a 44-year old patient previously treated for squamous cell carcinoma of the tongue, subsequent to proper surgical debridement. We report post-operative two-year follow-up demonstrated by panoramic X-ray which showed regain of the mandibular bone continuity with a complete repair of the necrotic defects. We conclude that this case illustrates an incident of successfid regeneration of ORN critical-sized defect of the mandible by autologous PRP gel.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP-2007-2.3-1 | Award Amount: 15.47M | Year: 2008

Angiogenesis underlies almost all biological processes of morphogenesis, including those in tissue repair and regeneration. Physiological angiogenesis is controlled by a complex interplay between cells and their environment: the extracellular matrix (ECM) provides signaling via numerous ECM adhesion molecules and growth factors bound to ECM polysaccharide components; and cells locally degrade and remodel the ECM to create pores into which angiogenic endothelial cells migrate. This observation, that physiological angiogenesis proceeds in response to solid-phase cues motivates our approach, namely creating bioactive resorbable materials as scaffolds that contain bound molecular signals to induce physiological angiogenesis in situations of tissue repair and regeneration. In some of our scaffold materials, porosity is inherent by virtue of fabrication, and in others porosity is created by cell-associated proteolysis as it is in physiological angiogenesis. All materials will be designed so as to be injectable or implantable into the human body. In some work, the final injectable/implantable material will comprise only materials and bioactive biomolecular signals, and in other cases it will also comprise cells. Thus, the concept of ANGIOSCAFF is to create materials that are bioresponsive (to environmental signals including pH and redox potential, and to cellular signals such as proteases), that are bioactive (by virtue of bound peptide or recombinant protein adhesion ligands and bound and releasable growth factors), and that are capable of carrying cellular therapeutics. To realize ANGIOSCAFF, we have assembled a team comprising both industrial and academic expert groups in biomaterials design and development, experts in the science and application of angiogenesis, in imaging in animal models, and in applications demanding biomaterials-based, angiogenesis-demanding tissue engineering therapies, including repair of bone, skin, cardiac muscle, skeletal muscle and nerve.


Muraglia A.,Biorigen Srl | Ottonello C.,Biorigen Srl | Spano R.,Biorigen Srl | Dozin B.,IRCCS AOU San Martino IST Instituto Nazionale per la Ricerca sul Cancro | And 5 more authors.
Platelets | Year: 2014

Serum of animal origin and in particular fetal bovine serum is the most commonly utilized cell culture medium additive for in vitro cell growth and differentiation. However, several major concerns have been raised by the scientific community regarding the use of animal sera for human cell-based culture applications. Among the possible alternatives to the animal serum, platelet-derived compounds have been proposed since more than 10 years. Nevertheless, the high degree of variability between the different platelet preparations, and the lack of standardized manufacturing and quality control procedures, made difficult to reach a consensus on the applicability of this novel cell culture medium supplement. In this study, we describe the preparation of a standardized platelet-rich plasma (PRP) derivative obtained starting from human-certified buffy coat samples with a defined platelet concentration and following protocols including also freeze-drying, gamma irradiation and biological activity testing prior the product release as cell culture medium additive. Biological activity testing of the different preparations was done by determining the capability of the different PRP preparations to sustain human bone marrow mesenchymal stem cell (MSC) clone formation and proliferation. Taking advantage of a developed MSC in vitro clonogenicity test, we also determined biological activity and stability of the freeze-dried gamma-sterilized PRP preparations after their storage for different times and at different temperatures. The PRP effects on cell proliferation were determined both on primary cell cultures established from different tissues and on a cell line. Results were compared with those obtained in "traditional" parallel control cultures performed in the presence of bovine serum [10% fetal calf serum (FCS)]. Compared to FCS, the PRP addition to the culture medium increased the MSC colony number and average size. In primary cell cultures and in cell line cultures, the PRP promoted cell proliferation also in conditions where the FCS had not a proliferation stimulating effect due to either the nature of the cells and the tissue of origin (such as human articular chondrocytes from elderly patients) or to the critical low density cell seeding (such as for HeLa cells). In summary, the standardized PRP formulation would provide an "off-The-shelf" product to be used for the selection and expansion of several cell types also in critical cell culture conditions. © 2014 Informa UK Ltd. All rights reserved.


PubMed | University of Genoa, Biorigen S.r.l. and IRCCS AOU San Martino IST Instituto Nazionale per la Ricerca sul Cancro
Type: | Journal: Journal of tissue engineering and regenerative medicine | Year: 2016

Chronic skin ulcers, consequence of diabetes and other pathological conditions, heavily compromise the patients life quality and represent a high and constantly growing cost for National Health Services. Autologous Platelet Rich Plasma (PRP), has been proposed to treat these lesions. The absence of guidelines for the PRP production and the need of a fresh preparation for each treatment lead us to develop a protocol for the production of an allogenic PRP based bioactive membrane (BAM), standardized for platelet concentration and growth factor release. This work compares BAM obtained starting from two different platelet concentrations. We did not observe a direct correlation between the amount of growth factors released by BAM in vitro and the initial platelet count. However, different release kinetics were noticed for different growth factors, suggesting that they were differently retained by the two BAM. The angiogenic potential of both BAM was determined by Luminex Angiogenesis Assay. The biological activity of the factors released by the two BAM was confirmed by cell proliferation and migration. A diabetic mouse chronic ulcer model was used to define the best PRP therapeutic dose in vivo. Both BAM induced wound healing by increasing the thickness of the regenerated epidermis and the vessel number. However, a too high platelet concentration resulted in a slowdown of the membrane resorption that interfered with the skin healing. Overall our results indicate that the BAM could represent a natural and effective wound healing tool for the treatment of skin ulcer.


Muraglia A.,Biorigen S.r.l. | Todeschi M.R.,Biorigen S.r.l. | Todeschi M.R.,University of Genoa | Papait A.,University of Genoa | And 9 more authors.
Cytotherapy | Year: 2015

Background aims: Platelet derivatives have been proposed as alternatives to animal sera given that for cell therapy applications, the use of fetal bovine/calf serum (FBS/FCS) is subjected to severe limitations for safety and ethical concerns. We developed a cell culture medium additive obtained by the combination of two blood-derived standardized components. Methods: A platelet lysate (PL) and a platelet-poor plasma (PPP) were produced in a lyophilized form. Each component was characterized for its growth factor content (platelet-derived growth factor-BB/vascular endothelial growth factor). PL and PPP were used as single components or in combination in different ratio at cumulative 5% final concentration in the culture medium. Results: The single components were less effective than the component combination. In primary cell cultures (bone marrow stromal cells, adipose derived adult stem cells, osteoblasts, chondrocytes, umbilical cord-derived mesenchymal stromal cells, lymphocytes), the PL/PPP supplement promoted an increased cell proliferation in respect to the standard FCS culture in a dose-dependent manner, maintaining the cell functionality, clonogenicity, phenotype and differentiative properties throughout the culture. At a different component ratio, the supplement was also used to support proliferation of a cell line (U-937). Conclusions: The PL/PPP supplement is an efficient cell culture medium additive that can replace FCS to promote cell proliferation. It can outdo FCS, especially when adopted in primary cultures from tissue biopsies. Moreover, the dual component nature of the supplement allows the researcher to determine the more appropriate ratio of the two components for the nutritional and functional requirements of the cell type of interest. © 2015 International Society for Cellular Therapy.


PubMed | University of Genoa, Biorigen S.r.l. and IRCCS AOU San Martino IST Instituto Nazionale per la Ricerca sul Cancro
Type: Journal Article | Journal: Cytotherapy | Year: 2015

Platelet derivatives have been proposed as alternatives to animal sera given that for cell therapy applications, the use of fetal bovine/calf serum (FBS/FCS) is subjected to severe limitations for safety and ethical concerns. We developed a cell culture medium additive obtained by the combination of two blood-derived standardized components.A platelet lysate (PL) and a platelet-poor plasma (PPP) were produced in a lyophilized form. Each component was characterized for its growth factor content (platelet-derived growth factor-BB/vascular endothelial growth factor). PL and PPP were used as single components or in combination in different ratio at cumulative 5% final concentration in the culture medium.The single components were less effective than the component combination. In primary cell cultures (bone marrow stromal cells, adipose derived adult stem cells, osteoblasts, chondrocytes, umbilical cord-derived mesenchymal stromal cells, lymphocytes), the PL/PPP supplement promoted an increased cell proliferation in respect to the standard FCS culture in a dose-dependent manner, maintaining the cell functionality, clonogenicity, phenotype and differentiative properties throughout the culture. At a different component ratio, the supplement was also used to support proliferation of a cell line (U-937).The PL/PPP supplement is an efficient cell culture medium additive that can replace FCS to promote cell proliferation. It can outdo FCS, especially when adopted in primary cultures from tissue biopsies. Moreover, the dual component nature of the supplement allows the researcher to determine the more appropriate ratio of the two components for the nutritional and functional requirements of the cell type of interest.


Patent
Biorigen S.R.L. | Date: 2012-02-10

A bio-membrane with angiogenic activity for implant in tissue regeneration and repair, including bone reconstruction and the repair of skin and soft tissue lesions is described, essentially constituted by a gel able to provide support and growth and/or differentiation and/or angiogenic factors for the full in vivo functionality of the cell, containing also mesenchymal stem/precursor cells, an implant device for reconstructive surgery of bone tissue, of skin and soft tissue lesions which comprises the bio-membrane, and a method for its obtainment. Use of the gel alone for tissue regeneration and of adhesive plasters that comprise it is also described.

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