UNIVERSITÀ DEGLI STUDI DI PAVIA

SHAPE MEMORY ENGINEERED TISSUE (SMET)

The present invention consists of a method for the production of a shape memory engineered tissue (SMET) through the use of electrospun polymeric matrix capable of transiently modifying its shape, following the application of an external stimulus such as temperature, and at the same time capable of supporting the delivery of cells and/or drugs. SMET can be used as as mini-invasive device for tissue regeneration.

Patent Status

Pending

Priority Number

IT102021000019256

Priority Date

20/07/2021

License

ITALY

Market

The global Minimally Invasive Surgery (MIS) Marker size is estimated to be USD 39.38 billion in 2019 and is predicted to reach USD 90.89 by 2030 with a CAGR of 7.9% form 2020 – 2030. The factors such as constant development in the MIS devices, faster recovery and increased success rates are further expected to contribute the growth of MIS. Among the handheld instrument devices for MIS we place SMET device. Furthermore, SMET is classified as Advanced Therapy Medicinal Products (ATMP) an industry which was rated USD 7.9 billion in 2020 and has 13.2% growth prospect from 2021 to 2028.

Problem

Many traditional surgical operations (such as esophagectomy, fetoscopy, vascular and abdominal surgery, etc) require invasive procedure that can be dangerous for patient’s survival and lengthen recovery times. Moreover, tissue regeneration sometimes cannot reach physiological activities recovery due to the onset of chronic inflammation, foreign tissue rejection and lack of pro-regenerative stimuli. A less invasive and more targeted action is required to achieve a better healing. The present invention is proposed in the biomedical field as a shape memory engineered tissue (SMET) capable of being implanted through minimally invasive surgery (MIS), such as laparoscopy and robotic surgery. SMET, thanks to its unique stimulus-induced property to change shape and the simultaneous conveyance of biological material, is a versatile product to promote tissue regeneration.

Current Technology Limits

One weakness of the SMET is the fact that it requires GMP (Good Manufacturing Practice) laboratories and a GMP production line in order to be sterilized, since the cost of GMP production is higher compared to other solutions that do not require cell.

SMET is looking for a sponsor or someone that can provide his support and help for further R&D and In Vivo tests applications.

Killer Application

SMET is a versatile and potentially usable device in precision medicine. The SMET dimensions and geometries can be modulated according to the type of damage or MIS intervention required. Furthermore, the biological material (e.g. cells) or drug delivered by SMET can be decided depending on the patient’s needs.

Our Technology and Solutions

Shape memory engineered tissue (SMET) is able to modify its configuration in response to specific external stimuli (Temperature) and perform local regenerative activity. SMET is designed to perform as mini-invasive device for tissue regeneration. SMET is made by electrospinning technique using the copolymer poly-L-lactide-co-ε-caprolactone. A shape memory treatment (SMT), consisting of a cycle of high (T° >Tg°) and low temperature (T° < Tg°), leads to the shape change inducing rolled conformation. After implantation, at body temperature, SMET unrolls and completely regains its original shape.

Advantages

SMET exhibits stable rolled conformation until its application at physiologic body temperature
SMET guarantees excellent cell adhesion and proliferation during all the shape transition phases
SMET prevent tissue rejection through the use of autologous cells
SMET guarantees tissue regeneration avoiding secondary surgery for its removal
SMET fits well with instrument used in minimally invasive surgery
SMET application in MIS reduce invasiveness of traditional surgical techniques
SMET can be design for a personalize medicine application
SMET decrease patient recovery time and health costs

Roadmap

The next steps before the industrial development of smet require

1) in vivo immuno-histological characterization

2) long-term in vivo studies

A GMP facility is required for the industrialization phase

For each type of specific application and intervention in MIS a dedicated study is required starting from the design, geometry and size of SMET, type of cell for engineering (MSCs or differentiated cell).

Review the Technology

TRL 1

TRL 2

TRL 3

TRL 4

TRL 5

TRL 6

TRL 7

TRL 8

TRL 9

TRL

Team

Rossella Dorati

Assistant professor at the Department of Drug Sciences, University of Pavia

She achieved her MSc and PhD in Medicinal Chemistry and Pharmaceutical Technology. Her recent research focuses on drug delivery systems, and on novel topical formulations for wound healing. This includes physicochemical characterization, stability, in vitrodrug release and biological evaluation. She works in collaboration with Dr. Leung Kai US Army Institute of Surgical Research, San Antonio, Texas (USA), where she was Visiting Formulation Scientist from Oct 2015 to Oct 2017, working on the Development of Topical Formulation as Anti-scarring Treatment for Deep Partial-Thickness Burns.

Read bio

Ida Genta

Associate professor of pharmaceutics at the Department of Drug Sciences, University of Pavia.

Achieved MSc and PhD in Medicinal Chemistry and Pharmaceutical Technology, and post-graduate diploma in Industrial Pharmaceutics. Her research interests involve polymeric micro- and nano-particulate drug delivery systems, loaded with both small drugs and macromolecules. Studies includes morphological, physicochemical and dimensional characterization of nano-systems as well as their in vitro stability, drug release and ex-vivo biological evaluation. More recently, her work deals with the development of smart nano-systems (targeting EGFR or CD44) by innovative and easy-scalable preparation methods based on microfluidic process.

Read bio

Bice Conti

Full professor of pharmaceutics at the Department of Drug Sciences, University of Pavia.

MSc in Medicinal Chemistry and Pharmaceutical Technology and postgraduate degree in Industrial Pharmacy. Her research and expertise focus on biodegradable polymers for biomedical applications and tissue engineering applications, their processing and physicochemical characterization by e.g. Gel permeation Chromatography (GPC), Differential Scanning Calorimetry (DSC). In these years, she carried on collaborations with pharmaceutical and medical devices companies such as Ceva-Vetem (Agrate Brianza, Italy), Rottapharm Biotec (Monza, Italy), US-WorldMeds (Louisville, USA), Geistlich Pharma AG (Root-Langenbold CH).

Read bio

Maria Antonietta Avanzini

Biologist Director at the Pediatric Oncohematology Foundation IRCCS Policlinico San Matteo, Pavia.

Degree in Biological Sciences. Postgraduate Diploma in Histochemistry and Cytochemistry (1985, University of Pavia). Research Doctorate in Developmental Medical Sciences at the Immunology Laboratory of the Pediatric Clinic (1991, University of Pavia). Specialization Diploma in Food Science (2001, University of Pavia. Attended the Clinical Immunology Laboratory of the University of Gothenburg (Sweden) as a researcher from September 1985 to September 1986. Experience in the development and standardization of immunoenzymatic techniques (ELISA and ELISPOT), in flow cytometry, cell cultures, expansion and characterization of mesenchymal stromal cells.

Read bio

Marco Benazzo

Full professor of otorhinolaryngology and Dean of the School of Medicine of the University of Pavia, and director of the Department of of Clinical-Surgery of I.R.C.C.S Policlinico S.Matteo, Pavia.

Currently full professor of otorhinolaryngology, Dean of the School of Medicine of the University of Pavia, and director of the Department of of Clinical-Surgery of I.R.C.C.S Policlinico S.Matteo, Pavia. His scientific research is currently addressed to head and neck oncology and regenerative medicine.

Read bio

Silvia Pisani

Researcher at Fondazione IRCCS Policlinico San Matteo, Pavia and Dept. of Drug Sciences, University of Pavia.

Degrees in Pharmacy and in CTF at University of Pavia. Achieved PhD in Chemical and Pharmaceutical Sciences at the University of Pavia in 2019 with a project focused on “Tissue Regeneration: Investigating Drug Delivery Systems and New Scaffolds Manufacturing 3Technologies”. Researches involve electrospinning technique and rapid prototyping for scaffold manufacturing for tissue regeneration and drug delivery, their biologic and morphologic characterization. I worked in the research groups of Prof. Kit Parker DBG - Harvard School of Engineering and Applied Sciences, Boston (USA) and Prof. Adriele Prina-Mello School of Medicine, Trinity College (Ireland). I was involved in NFFA scholarship (Horizon 2020 EU) at The Foundation for Research and Technology – Hellas (FORTH).

Read bio