Metal-Organic Framework (MOF)-Based Biomaterials for Tissue Engineering and Regenerative Medicine

Abstract

The synthesis of Metal-organic Frameworks (MOFs) and their evaluation for various applications is one of the largest research areas within materials sciences and chemistry. Here, the use of MOFs in biomaterials and implants is summarized as narrative review addressing primarely the Tissue Engineering and Regenerative Medicine (TERM) community. Focus is given on MOFs as bioactive component to aid tissue engineering and to augment clinically established or future therapies in regenerative medicine. A summary of synthesis methods suitable for TERM laboratories and key properties of MOFs relevant to biomaterials is provided. The use of MOFs is categorized according to their targeted organ (bone, cardio-vascular, skin and nervous tissue) and whether the MOFs are used as intrinsically bioactive material or as drug delivery vehicle. Further distinction between in vitro and in vivo studies provides a clear assessment of literature on the current progress of MOF based biomaterials. Although the present review is narrative in nature, systematic literature analysis has been performed, allowing a concise overview of this emerging research direction till the point of writing. While a number of excellent studies have been published, future studies will need to clearly highlight the safety and added value of MOFs compared to established materials for clinical TERM applications. The scope of the present review is clearly delimited from the general 'biomedical application' of MOFs that focuses mainly on drug delivery or diagnostic applications not involving aspects of tissue healing or better implant integration.

Keywords: biomaterial; bone; cardio-vascular; metal-organic frameworks; nervous tissue; regenerative medicine; tissue engineering.

FIGURE 1

Schematic on the present and envisioned use of MOFs as a component of implants or biomaterial compositions with applications in Tissue Engineering and Regenerative Medicine (TERM). The crystal structure of the prototypical MOF Zeolitic Imidazolate Framework 8 (ZIF-8) is depicted along the [111] crystallographic direction (left side) and HKUST-1 also known as Cu-BTC is depicted along the [001] crystallographic direction. These two different structures have been most frequently applied to TERM research and represent the diverse class of MOFs. In particular, simple exposure of osteoblast like cells to ZIF-8 increases ALP activity (Chen et al., 2017a), Cu-BTC can decrease adherence and activation of platelets (Fan et al., 2019) and also accelerates skin wound closure (Xiao et al., 2018).

FIGURE 2

Application of MOFs to improve bone implants through continuous release of earth alkaline ions promoting bone regeneration and biomineralization (Joseph et al., 2019) (A), facilitating osteo-induction and -integration through favorable upregulation of relevant genes in presence of specific MOFs (Li et al., 2020) (B) and providing improved tissue integration and an anti-bacterial effect (Chen et al., 2017a) (C).