Technology Offers

Tissue-specific hydrogel-based ECM hybrid material used as a precisely fitting implant for the treatment of extensive tissue defects

Abstract

This technology provides the fundamental for a native wound gel that is capable of comprehensive treatment of deep and large area wounds. Due to its tissue-specific composition and high bioactivity it ensures efficient healing. Glycobiological modifications of the tissue-specific hydrogel result in a customizable wound gel which could replace a skin transplant in many cases.

Background

If skin injuries extend to the subcutaneous tissue (subcutis), patients will most likely need an autologous skin transplant (transplantation of the patient's own skin). This usually has far-reaching consequences for the patient, and also quickly reaches natural and aesthetic limits.

Problem

The clinical treatment of deep and extensive wounds, e.g. after burns, remains challenging. Conventional synthetic hydrogels often do not adequately reflect the complexity and regenerative properties of the natural ECM.

Solution

Compared to conventional, synthetic hydrogels, this material is based on an ECM produced in the laboratory using the patient's own cells. Based on a patent-pending technology for the production of an extracellular matrix (ECM) with specifically addressable functional groups ("clickECM"), the basis for a native wound gel has now been created that could also close deep and large area wounds and, due to its tissue-specific composition and high bioactivity, ensure efficient healing.
During the synthesis of the matrix by the patient's own cells, functional groups are incorporated into this matrix by metabolic glycoengineering. These specifically addressable functional groups can later be used to link bioactive molecules or other substances according to the intended application.
For example, photo-polymerizable biopolymers bound to the ECM could, after optimal filling of the wound bed, ensure precise gelling and closing of the wound (precisely fitting wound closure). The flexibility of the material also makes it possible to precisely treat contour defects. Furthermore, this functionalized matrix can be "loaded" or equipped with various active ingredients that expedite wound healing or have an antimicrobial effect, for example.

The new biomaterial has already been successfully mixed with other hydrogels and built up into stable 3D models. These were cell-compatible and biocompatible in initial trials. In recent studies (Nellinger et al. 2021), it was also shown that it is possible to modify a cell-derived ECM by glycoengineering with dienophiles and to incorporate a bioactive enzyme via an IEDDA reaction. Neither did the monosaccharide derivatives used exhibit cytotoxic effects, nor were cytotoxic catalysts necessary for the process of functionalisation. Furthermore, it could be shown that those functional groups themselves have no effect on basic cell behaviour such as survival, metabolic activity and proliferation.
This means that in future, an ECM can be equipped with growth factors, cross-linkers and other molecules and thus becomes a new functional biomaterial that has great potential for a variety of applications in the field of tissue engineering and regenerative medicine

Schematic illustration of the treatment of a deep wound using ECM hydrogel-based hybrid material as an accurately fitting wound closure. The wound is precisely filled with the hybrid material and gelled. The body's own cells can migrate into the material and restore the missing tissue. As a result, wounds can heal without residual deformities or scars [Source: Universität Reutlingen].
Schematic illustration of the treatment of a deep wound using ECM hydrogel-based hybrid material as an accurately fitting wound closure. The wound is precisely filled with the hybrid material and gelled. The body's own cells can migrate into the material and restore the missing tissue. As a result, wounds can heal without residual deformities or scars [Source: Universität Reutlingen].

Advantages

  • highly compatible biological material that promotes wound healing with the patient’s own cells
  • contour defects can be corrected
  • flexibly adaptable through specifically addressable functional groups
  • active ingredients can be incorporated

Application

This innovative further development sets the course for effective treatment of extensive tissue defects such as third-degree burns, chronic wounds, chemical burns, etc.

Find out more

Nellinger, S., Rapp, M.A., Southan, A., Wittmann, V. and Kluger, P.J. (2021); “An Advanced ‘clickECM’ That Can be Modified by the Inverse-Electron-Demand Diels-Alder Reaction.” https://doi.org/10.1002/cbic.202100266

Keller, Silke & Wörgötter, Katharina & Liedek, Anke & Kluger, Petra & Bach, Monica & Tovar, Günter & Southan, Alexander (2020); “Azide-Functional Extracellular Matrix Coatings as a Bioactive Platform for Bioconjugation.”  https://doi.org/10.1021/acsami.0c04579

Keller, Silke & Bakker, Tomke & Kimmel, Benjamin & Rebers, Lisa & Götz, Tobias & Tovar, Günter E. M & Kluger, Petra & Southan, Alexander. (2020); “Azido‐functionalized gelatin via direct conversion of lysine amino groups by diazo transfer as a building block for biofunctional hydrogels.” https://doi.org/10.1002/jbm.a.37008

Nellinger, Svenja & Keller, Silke & Southan, Alexander & Wittmann, Valentin & Volz, Ann-Cathrin & Kluger, Petra (2019). „Generation of an azide-modified extracellular matrix by adipose-derived stem cells using metabolic glycoengineering.”  https://doi.org/10.1515/cdbme-2019-0099

S.M. Ruff, S. Keller, D.E. Wieland, V. Wittmann, G.E.M. Tovar, M. Bach, P.J. Kluger (2017),“clickECM: Development of a cell-derived extracellular matrix with azide functionalities” https://doi.org/10.1016/j.actbio.2016.12.022

 

Exposé
Contact
Anne Böse, M.Sc.
TLB GmbH
Ettlinger Straße 25
76137 Karlsruhe | Germany
Phone +49 721-79004-0
boese(at)tlb.de | www.tlb.de
Development Status
Proof of concept / TRL3
Patent Situation
EP 3218025 B1 granted
DE, FR, GB validated
Reference ID
14/058TLB
Service
The scientists are now looking for an industrial partner in order to develop a marketable product from this promising approach. Technologie-Lizenz-Büro (TLB) GmbH is commissioned with the exploitation on behalf of the patent holders and is seeking industry partners to enter into cooperation in order to develop the product for the market or for licensing.