Silk Fibroin 3D Microparticle Scaffolds with Bioactive Ceramics: Chemical, Mechanical, and Osteoregenerative Characteristics

Abstract

Bone regeneration in large bone cavities presents a major challenge. These bony voids are either filled with an autograft/ allograft (patient's own bone from another anatomical location or cadaveric bone, respectively), or synthetic bone graft substitute called "bone void filler." Autografts are the 'gold standard' for bone grafting, but have inherent limitations of donor site morbidity and limited supply. [1] More recently, synthetic ceramics have shown promise for this application of bone void filling because of their chemical similarity to ceramics present in natural bone. Commonly used bioceramics include hydroxyapatite (HA), beta tricalcium phosphate (TCP), and more recently calcium sulfate (CaS). These materials are biocompatible, and support cell adhesion, proliferation, and growth of bone cells. Although these bioceramics are used as bone void fillers, they have certain limitations: they are intrinsically brittle and lack the required mechanical properties. Also, some of them have faster bioresorption rate (e.g., CaS and TCP), whereas others do not completely bioresorb (e.g., HA). In this context, to achieve native bone-like properties, current trend in bone tissue engineering (BTE) is to use a composite of bioceramic and a biocompatible polymer. [2,3] Silk fibroin (SF)-a natural biopolymerhas come up as potential candidate for BTE, owing to its biocompatibility, mechanical properties, tunable biodegradation rate, and ease of processability. The silk from the Bombyx mori silkworm, commonly known as a mulberry silkworm, can be produced with good quality in large quantities. [4-6] Efficacy of SF-based biomaterials has been proven in various tissue regeneration models. [7,8] SF can be easily modulated to obtain required functionality and different forms. [9,10] Different SF-based biomaterials including SF films, [11] SF-3D scaffold, [12,13] and SF-reinforced biomaterials [14] have proven to be successful for bone regeneration purpose. We have earlier reported a method to prepare silk fibroin microparticle scaffolds that have shown a high potential in BTE. [12] These SF microparticle scaffolds have excellent mechanical properties, pore interconnectivity, and a superior ability to promote osteoregeneration. The objective of this work was to prepare regenerated silk fibroin (RSF) microparticle scaffolds filled with nano-HA or CaS. [12,13] The addition of these fillers would further enhance the mechanical properties of these scaffolds and would thereby contribute toward the osteoregenerative potential. We compare and evaluate the performance of these microparticles and scaffolds vis-à-vis pure SF scaffolds. We have characterized the microparticles and their scaffolds for the