Periodic Reporting for period 1 - SHIFT (Shaping Innovative Designs for Sustainable Tissue Engineering Products)
Berichtszeitraum: 2021-09-01 bis 2023-08-31
Shaping Innovative Designs for Sustainable Tissue Engineering Products - SHIFT (https://r1.unitn.it/shift/) represents the second phase of SCA-RISE REMIX (GA 778078 - 2017-2021) and aims to build on the breakthroughs and developments achieved by REMIX. REMIX researched and confirmed the potential of natural origin material (i.e. silk proteins, collagen, keratin, chitosan, and marine organism-derived polymers) for Tissue Engineering and Regenerative Medicine applications.
Starting from these natural origin materials, SHIFT aims to design innovative sustainable natural-based constructs that enhance angiogenesis, focusing on the treatment of skin and bone. Prototypes will be fabricated considering scalability, costs, and regulatory issues.
The target applications of the products are tissues with fast angiogenesis requirements or control, such as large bone defects and skin wounds. Both cases addressed are relevant, since the aging population who suffer from major degenerative diseases of bone and skin is rising globally, whether there are no current therapeutic solutions for patients.
The strategies implemented to achieve the goal are:
• producing prototypes considering regulative and quality control framework (GMP and ISO) in close collaboration with the industry and clinicians.
• standardization of the protocols for purification of raw materials from the waste of the textile and food industry, and the creation of new opportunities for re-using industrial waste;
• application of the principles of green chemistry;
• extensive training program for ESRs (winter/summer schools, seminars) covering different topics, such as TERM, technologies, regulations for product development, spin-offs, and venture capitals.
• Dissemination of results in International context, scientific as well as biomed companies.
Starting from these natural origin materials, SHIFT aims to design innovative sustainable natural-based constructs that enhance angiogenesis, focusing on the treatment of skin and bone. Prototypes will be fabricated considering scalability, costs, and regulatory issues.
The target applications of the products are tissues with fast angiogenesis requirements or control, such as large bone defects and skin wounds. Both cases addressed are relevant, since the aging population who suffer from major degenerative diseases of bone and skin is rising globally, whether there are no current therapeutic solutions for patients.
The strategies implemented to achieve the goal are:
• producing prototypes considering regulative and quality control framework (GMP and ISO) in close collaboration with the industry and clinicians.
• standardization of the protocols for purification of raw materials from the waste of the textile and food industry, and the creation of new opportunities for re-using industrial waste;
• application of the principles of green chemistry;
• extensive training program for ESRs (winter/summer schools, seminars) covering different topics, such as TERM, technologies, regulations for product development, spin-offs, and venture capitals.
• Dissemination of results in International context, scientific as well as biomed companies.
The work performed in the reporting period is described by referring to the work packages.
WP 1. Selection of sustainable materials sources and Biopolymers isolation sustainable protocols were achieved for all polymers selected (chitosan from crab, shrimp shells, collagen from squid, codfish skin, ovine tendon) and defined characterization methods, taking into consideration green chemistry, standardization.
GMP (Good Manufacturing Practice) protocol for the standard production of local production of medical grade Bombyx mori silk was started and implemented in Rovereto (TN) Italy under the supervision of UNITN and Thai silk under the supervision of CU.
Definition and optimization protocol based on green chemistry to produce Demineralized Bone Matrix derived from the chicken was studied and written.
WP 2. The physical properties, cost, reproducibility, and absence of contaminants of the extracted chitosan and collagen of marine origin were evaluated. Hydrogels composed of hyaluronic acid, silk fibroin, and a blend of the two, functionalized with the natural chemical compound icariin were designed, developed, and characterized physically and biologically.
Silk fibroin-hyaluronic acid blends were also studied for 3D extrusion printing, through swelling and printability tests.
Hydroxyapatite (synthetic and biogenic from mussel shell sources) and methacrylate silk fibroin sponges were produced for bone scaffold applications.
Thus, Definition of the fabrication technology on the base of the material type selected in WP1 and considering their scalability and costs, setting up the selected fabrication methods enabling specific hardware requirements), Tuning and optimization of the fabrication conditions, and Fabrication of the prototype on the base of the intended final application and function, were faced during the first year of the project.
WP 3. it was achieved through the development of a survey of medicinal plants from Mongolian traditional medicine prescription, focusing on those species likely to be of importance in medicine, food, and nutrition products. The activity was indeed focused on the identification and evaluation of nature-derived molecules with pharmacological impact. This study was also useful to start working on Medicinal plants culture. The first steps were the Protocol design and Technology development were approached by studying the extract of Allium mongolicum Regel Regel (Asian wild onion) as a substrate for endothelial cells and new capillary assembling.
WP 4. The biological evaluation performed were done in in vitro cell culture by following selected and optimized protocols. Commercially available human cells were used. Samples were tested in particular to evaluate toxicity, cell adhesion and proliferation, production of extra cellular matrix (ECM) marker molecules. The in vitro testing/validation/upscale in ongoing.
WP 1. Selection of sustainable materials sources and Biopolymers isolation sustainable protocols were achieved for all polymers selected (chitosan from crab, shrimp shells, collagen from squid, codfish skin, ovine tendon) and defined characterization methods, taking into consideration green chemistry, standardization.
GMP (Good Manufacturing Practice) protocol for the standard production of local production of medical grade Bombyx mori silk was started and implemented in Rovereto (TN) Italy under the supervision of UNITN and Thai silk under the supervision of CU.
Definition and optimization protocol based on green chemistry to produce Demineralized Bone Matrix derived from the chicken was studied and written.
WP 2. The physical properties, cost, reproducibility, and absence of contaminants of the extracted chitosan and collagen of marine origin were evaluated. Hydrogels composed of hyaluronic acid, silk fibroin, and a blend of the two, functionalized with the natural chemical compound icariin were designed, developed, and characterized physically and biologically.
Silk fibroin-hyaluronic acid blends were also studied for 3D extrusion printing, through swelling and printability tests.
Hydroxyapatite (synthetic and biogenic from mussel shell sources) and methacrylate silk fibroin sponges were produced for bone scaffold applications.
Thus, Definition of the fabrication technology on the base of the material type selected in WP1 and considering their scalability and costs, setting up the selected fabrication methods enabling specific hardware requirements), Tuning and optimization of the fabrication conditions, and Fabrication of the prototype on the base of the intended final application and function, were faced during the first year of the project.
WP 3. it was achieved through the development of a survey of medicinal plants from Mongolian traditional medicine prescription, focusing on those species likely to be of importance in medicine, food, and nutrition products. The activity was indeed focused on the identification and evaluation of nature-derived molecules with pharmacological impact. This study was also useful to start working on Medicinal plants culture. The first steps were the Protocol design and Technology development were approached by studying the extract of Allium mongolicum Regel Regel (Asian wild onion) as a substrate for endothelial cells and new capillary assembling.
WP 4. The biological evaluation performed were done in in vitro cell culture by following selected and optimized protocols. Commercially available human cells were used. Samples were tested in particular to evaluate toxicity, cell adhesion and proliferation, production of extra cellular matrix (ECM) marker molecules. The in vitro testing/validation/upscale in ongoing.
The development of a successful sustainable treatment for bone and skin regeneration, based on tissue engineering would improve the life quality of a large part of the population with strong social impact. The results of SHIFT would affect not only the aging population who suffer from major degenerative diseases but also the life of younger patients who is now strictly limited by the disease.
A sensible scientific impact was achieved the development of an effective treatment for bone defects and wound healing would also result in economic implications and impact. Indeed, health care costs are high as patients often require acute care in intensive care unit facilities, higher rates of complications related to injury, rehabilitation, and health services as well as chronic care costs from long-term disability. The proposed 3D bioactive constructs will combine vascularization technology with antimicrobial properties and tissue regeneration.
SHIFT will also result in a breakthrough in the development of personalized medical treatments.
The scientific progress achieved so far showed the healing potential of the structures that SHIFT the development, optimization, and standardization of protocols and (based on the previous REMIX project) by starting from natural resources and considering sustainability, green chemistry, absence of contaminants, e future products development, to meet the regulatory/quality aspects and achieve the production of medical-grade silk-based products. Activation of two Centers (UNITN and CU) for medical grade silk production (was certified for ISO 13485 (2016) for a Quality Management System (QMS) for the design and manufacturing of Medical Devices); definition of printing condition and ink parameter to fabricate scaffold with defined geometry, gradient; polymers functionalization with natural molecules (ex. icariin selected by MUST) to approach precision medicine strategy; processing methods for fabrication of matrices for wound healing and bone/osteochondral defect regeneration were designed by using several formulations. Hydroxyapatite from different sources (synthetic and biogenic from mussel shell) combined with silk fibroin resulted in a structure suitable for bone healing. Manufacturing of Nanoparticles based on chitosan and hyaluronic acid for wound healing applications. manufacturing optimization of ovine tendon collagen sponge.
Selection of protocols for in vitro evaluation to reduce cost and time of first step validation (scientific and economic impact).
A sensible scientific impact was achieved the development of an effective treatment for bone defects and wound healing would also result in economic implications and impact. Indeed, health care costs are high as patients often require acute care in intensive care unit facilities, higher rates of complications related to injury, rehabilitation, and health services as well as chronic care costs from long-term disability. The proposed 3D bioactive constructs will combine vascularization technology with antimicrobial properties and tissue regeneration.
SHIFT will also result in a breakthrough in the development of personalized medical treatments.
The scientific progress achieved so far showed the healing potential of the structures that SHIFT the development, optimization, and standardization of protocols and (based on the previous REMIX project) by starting from natural resources and considering sustainability, green chemistry, absence of contaminants, e future products development, to meet the regulatory/quality aspects and achieve the production of medical-grade silk-based products. Activation of two Centers (UNITN and CU) for medical grade silk production (was certified for ISO 13485 (2016) for a Quality Management System (QMS) for the design and manufacturing of Medical Devices); definition of printing condition and ink parameter to fabricate scaffold with defined geometry, gradient; polymers functionalization with natural molecules (ex. icariin selected by MUST) to approach precision medicine strategy; processing methods for fabrication of matrices for wound healing and bone/osteochondral defect regeneration were designed by using several formulations. Hydroxyapatite from different sources (synthetic and biogenic from mussel shell) combined with silk fibroin resulted in a structure suitable for bone healing. Manufacturing of Nanoparticles based on chitosan and hyaluronic acid for wound healing applications. manufacturing optimization of ovine tendon collagen sponge.
Selection of protocols for in vitro evaluation to reduce cost and time of first step validation (scientific and economic impact).