Versatile biocomposite scaffolds with osteogenic ions for bone regeneration in oral and maxillofacial surgery

Abstract

Autografts remain the gold standard for rehabilitating critical-sized bone defects in the oral and maxillofacial region (OMF). Despite considerable advances in biomaterials-based bone tissue engineering, they fail to offer viable alternatives to several unmet challenges. Most advanced synthetic bone substitutes (SBS’s) have not transcended the in vitro and animal study stage due to inferior performance and translational barriers, such as low scalability, high cost, regulatory restrictions, andlack of advanced facilities and operators. This study aims to offer clinically viable alternatives to address the challenges of bone tissue regeneration in the OMF region by developing ‘dual network composites’ (DNC’s) of calcium metaphosphate (CMP) –poly(vinyl alcohol) (PVA) / alginate with osteogenic ions: calcium, zinc and strontium. Single network composites (SNC’s) PVA/CMP with 1, 2, and 3 freeze-thawing (FT) cycles and 0, 10, and 20% (w/v) gelatin particles as the porogen, as well as guluronate-(G)and mannuronate-dominant (M) alginates chelated with Ca²⁺, Zn²⁺and Sr²⁺were tested for their physical properties for selection of optimal SNC formulation and alginate type for fabrication of DNC’s. SNC with 2FT and 10% (w/v) porogen and G-dominant alginate demonstrated optimal physical properties, thus were used to fabricate the DNC’s. Finally, PVA-CMP/alginate DNC’s with Ca²⁺/Zn²⁺/Sr²⁺ were developed, and their physicochemical, compressive (static and cyclic), water uptake, thermal, morphological, degradation and in vitro biological properties were characterised. They resulted in elastic 3D porous scaffolds, resembling a ‘spongy bone’ with fluid absorbing and versatile properties, enabling them to transport gases and nutrients across the construct, incorporate biofunctional agents and be easily shaped manually with simple tools to fit various anatomical complex bone defects. The excellent physicochemical properties with their in vitro cytocompatibility, render the DNC’s as potentially clinically viable SBS alternatives for bone regeneration in OMF surgery.

Date of Award	1 Jan 2021
Original language	English
Awarding Institution	King's College London
Supervisor	Sanjukta Deb (Supervisor) & Lucy Di-Silvio (Supervisor)