The RESTORE concept is to realize a new generation of smart 3D matrices for chondral lesions treatment. Key cutting-edge technologies will be employed into biocompatible 3D matrices to promote cartilage repair.

The competence and proof-of-concept owned by RESTORE consortium will lead to technology development reaching Technology Readiness levels (TRLs) 5-6 and to substantial clinical advances in regenerative medicine. Untreated or not-correctly treated chondral lesion will most likely progress towards osteoarthritis (OA), which affects 242 million people globally (costs/patient/year of 10,452€). RESTORE strives towards diminishing or delaying the onset of OA, thereby reducing hospitalization, number of surgeon interventions and time off work, which will lead to more cost-efficient health care, promote the wellbeing and active ageing of European population, and increase the EU attractiveness for research and investments in the field of regenerative medicine.

RESTORE emerges following constructive discussions between orthopaedic surgeons, tissue engineers, materials researchers and cellular biologists to answer pressing clinical needs.

RESTORE’s goal is to develop and validate in pre-clinical animal models, nanoenabled solutions for personalised cartilage regeneration. Different strategies will be undertaken to overcome the current challenges and unmet clinical necessities, in order to design the most efficient solution towards cartilage repair.

Which will be RESTORE’s impacts?

(I) Nanocarriers to deliver specific agents to promote cartilage repair

Challenge: Current treatments, such as implantation of engineered cartilage, trigger illicit biological responses that can lead to degradation of the construct.

Innovation: RESTORE will create tailored nanocarriers based on polymeric nanobiomaterials, designed to modulate undesirable biological events and integrate them in COPLA® Scaffold and to the bioink used for 3D bioprinting of human cartilage microtissues

Expected Outcomes:     

  • Tailored nanocarriers capable of mitigating illicit biological response.
  • Nanoenabled 3D matrices able of mitigating illicit biological response

(II) Stimuli-responsive nanobiomaterial tuned to physical stimulus

Challenge: The clinicians are looking forward to having access to 3D matrices with capabilities beyond biocompatibility and biomimetism, including external stimuli-responsive characteristics.

Innovation: RESTORE will explore stimuli-responsive nanobiomaterial to enhance cartilage repair via remote stimulation and integrate them in COPLA® Scaffold and to the bioink used for 3D bioprinting of human cartilage microtissues

Expected Outcomes:     

  • stimuli-responsive nanobiomaterials able to enhance cartilage repair via external stimulation
  • stimuli-responsive 3D matrices able to enhance cartilage repair via external stimulation

(III) Nanoenabled 3D matrices for mild and severe chondral lesions

Challenge: Chondral injuries can possess complex geometry/dimensions of injury and the larger the defect, higher the biomechanical requirements. This is a challenge to current treatments for chondral lesions.

Innovation: RESTORE will create smart 3D matrices for mild and severe chondral lesions, designed to adjust to the defect dimensions and biomechanical load. This will be accomplished in a two-front strategy: (1) 3D cartilage microtissues engineered via 3D bioprinting, and (2) COPLA® Scaffold (severe lesions) already present in the animal health market. These 3D matrices will integrate nanocarriers and stimuli-responsive nanobiomaterial.

Expected Outcomes:     

  • Nanoenabled 3D matrices for efficient repair of mild and severe chondral lesions

(IV) Cartilage 3Dbioprinting technology

Challenge: 3D Bioprinting technology still in early stages of research and development.

Innovation: RESTORE shall also improve bioprintability by optimizing the bioink for human cartilage and create a communication bridge between the clinical interests and industrial key players in Bioprinting technologies.

Expected Outcomes:     

  • Improved bioink and bioprinting protocols for human cartilage microtissues
  • 3D bioprinting technology advance toward clinical use (personalised medicine)

(V) Portable/wireless medical device able to remote control and monitor cartilage repair

Challenge: To develop portable technologies to mitigate and treat chondral lesions.

Innovation: RESTORE will develop a non-invasive and wearable medical device capable of activating smart nanobiomaterials allowing remote stimulation and monitoring of knee cartilage repair.

Expected Outcomes:     

  • Portable Medical Device for external stimulus and monitoring of cartilage repair

(VI) Database of patient-specific anatomical models for condyle lesions

Challenge: 3D printing of patient-specific anatomical features of tissues lesions provides surgeons with an immediate and intuitive understanding of even the most complex anatomical morphologies, enabling accurate planning and emulation of various surgical procedures.

Innovation: RESTORE WILL provide accurate 3D models (computer models as well as 3D printed models) of different chondral lesions and surrounding bone and soft tissue that can be used to develop, design, test and validate 3D printed microtissues that can fit patient specific lesions.

Expected Outcomes:     

  • Database of patient-specific anatomical models for condyle lesions

(VII) Regulatory aspects of smart nanobiomaterials

Challenge: The nanobiomaterials and biotechnology may define a new future in personalised medicine, still it is imperative to properly address the safety aspects regarding the toxicological impact to human health.

Innovation: RESTORE shall address the complex regulatory issues and access nanobiomaterials toxicity impact to human health.

Expected Outcomes:     

  • Reliable and reproducible data on the safety of the developed nanomaterials and nanoenabled 3D matrices.