Tuning Phage for Cartilage Regeneration

*Ayariga Joseph Atia, Abugri Daniel Azumah, Bedi Deepa and Derrick Dean*

## **Abstract**

The ever-broadening scope of phage research has left behind the simplistic view of studying phages as just model systems in phage biology to a much broader application ranging from ecological management to immunity. Improved throughput technology in crystallography and structural studies has helped our understanding of these systems as supramolecular machines that possess the capacity of selfassembly. The idea of phages as self-assembling supramolecular nano-machines that are bioactive biomaterials in characteristics, tunable and easily producible have lent its utility to recent fields such as regenerative medicine and tissue engineering. Due to low metabolic activity and slow nutrient diffusion within cartilage, damage to this tissue often inevitably consist of slow and delayed regeneration and healing, the restriction of blood from reaching most part of this tissue and the resultant limitations in the availability of oxygen and other essential amino acids dictates a very slow systemic metabolic response also since transports system in this tissue have to employ less speedy forms. Cartilage regeneration therefore is a huge challenge. This chapter takes a look at the application of the phage display technology in cartilage tissue regeneration.

**Keywords:** self-assembling, supramolecular, bioactive biomaterials, cartilage tissue regeneration, phage display

### **1. Introduction**

In nature, there exist remarkable structural complexities created out of selfassembly, for instance ice crystals from falling snow. In Molecular self-assembly, molecules adopt specific arrangement automatically without the direction of outside source. Phages like liquid crystals behave in such similar fashion, having the ability to self-assembly. Phages are viruses that infect bacterial cells, and also serve as most commercial vectors for recombinant DNA studies. Molecular self-assembly is a key concept in phage chemistry. The components of most phages or viruses in general have an assembly system which usually is directed through non-covalent interactions such as hydrogen bonding, hydrophobic forces, van der Waals forces, and electrostatic etc., leading to the formation of supramolecular assemblies composed of different shapes and sizes [1]. For instance, the interaction of the P22 phage tailspike protein with its capsid to form an infective phage is entirely non-covalent, however, once interaction is complete, bond reversibility is impossible [2]. Molecular self-assembly allows the construction of interesting molecular

topologies. This self-assembly system is also crucial in biological systems in the form of the formation of biomolecular condensates in living organisms, also found in oligomerization of protein subunits to form multimers of complex structures [3]. The application of this system therefore is a bottom-up approach, in which components of the phages are directed to self-assembly to achieve a programmed molecular topology, consisting of the desired shape and functional groups.

Most researches have delved into self-assembling filamentous phages, thus shed light on the pathways for their self-assembly. Filamentous bacteriophages such as the *Escherichia coli* K12-infecting Ff phages (F1, Fd or M13) replicate episomally and contain a circular single-stranded DNA packaged into long filaments. These phages are secreted into the environment without lysing their host. The knowledge of phages in general and filamentous phages in particular can played such a vital role in formulating new approaches in fabricating bioactive biomaterials [4] and providing for synergies and opportunities in phage display and tissue engineering approaches.
