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Institute of Bioengineering

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Co-culture Systems in Biomaterial Research & Regenerative Medicine with Professor James Kirkpatrick

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Date: 17 October 2019   Time: 14:00 - 15:00

Abstract:
Healing processes are a highly regulated series of biological activities in the so-called “regenerative niche” to restore structural and functional integrity, and involve the coordinated and sequential release of numerous biological signals from various cell types. Understanding these processes is a pre-requisite for progress in regenerative medicine. However, studying tissue reactions at the interface with biomaterials is complex and requires relevant cellular models. Our model systems, namely co-culture models with self-organizing ability [1, 2], have concentrated on an essential component of healing, namely vascularization. Thus, in studying bone regeneration, human osteoblasts or mesenchymal stromal cells which have been differentiated along the osteogenic lineage, interact in co-culture with human microvascular or progenitor endothelial cells to yield microvascular structures as a result of mutual stimulation [3]. The latter can also be formed on a 3D biomaterial scaffold in vitro, the resulting microvessels being rapidly integrated on implantation in vivo [4]. More recent research involves the role of the initial inflammatory reaction, and indicates that pro-inflammatory macrophages, as well as neutrophils, can accelerate this vascularization process [5,6]. Preliminary in vivo studies confirm that macrophages pre-cultivated on ceramics can stimulate the vascularization response following implantation. Further co-culture models have been established for the respiratory tract, e.g. the air-blood barrier, which is of interest for nanomedicine applications in which nanoparticles could be transported into the body by an inhalational route. The most complex of these air-blood barrier models involves the incorporation of macrophages, as these cells are also present in the alveoli [7,8]. In addition, co-cultures of respiratory basal epithelial progenitor cells with lung fibroblasts have been established as a model of upper respiratory tract regeneration and demonstrate formation of an intact, functional respiratory mucosa [9]. These interactions could be used for cellular colonization of decellularized upper airways. Other co-culture models based on self-organization have been developed to simulate the blood-brain [10], entero-capillary [11] and skin barriers [12]. Future developments must address the challenges of understanding the effects of, for example, ageing, multi-morbidity and medication on the healing reaction, and how these elements can be incorporated into meaningful in vitro model systems.

References
1. Kirkpatrick CJ et al. Biomaterials 2007; 28: 5193-5198
2. Kirkpatrick CJ. Tissue Engineering Part A 2014; 20: 1355-1357
3. Kirkpatrick CJ et al. Adv Drug Deliv Rev 2011; 63: 291-299
4. Ghanaati S et al. J Tissue Eng Reg Med 2011; 5/6: e136-143
5. Dohle E et al. E Cells & Mater J 2014; 27:149-164
6. Herath TDK et al. J Tissue Eng Regen Med 2018; 12(2):e1221-e1236
7. Kasper JY et al. JTERM 2017; 11: 1285-1297
8. Dohle E et al. Tissue Eng Part C Methods 2018; 24: 495-503
9. Pohl C. et al. Eur J Pharm Biopharm 2009; 72: 339-349
10. Freese C et al. Biomater Sci 2017; 5: 707-717
11. Kasper JY et al. Int J Mol Sci 2019; Jul 5;20(13). pii: E3301. doi:

Location:  GO Jones Building, Room LG1, Mile End Campus, Queen Mary University of London