Ductile silica/methacrylate hybrids for bone regeneration

Abstract

BioglassR was the first synthetic material capable of bonding with bone without fibrous encapsulation, and fulfils some of the criteria of an ideal synthetic bone graft. However, it is brittle and toughness is required. Here, we investigated hybrids consisting of co-networks of high crosslinking density polymethacrylate and silica (class II hybrid) as a potential new generation of scaffold materials. Poly(3-(methoxysilyl)propyl methacrylate) (pTMSPMA) and tetraethyl orthosilicate (TEOS) were used as sol-gel precursors and hybrids were synthesised with different inorganic to organic ratios (I h ). The hybrids were nanoporous, with a modal pore diameter of 1 nm. At I h = 50 %, the release of silica was controlled by varying the molecular weight of pTMSPMA while retaining a specific surface area above 100 m 2 g −1 . Strain to failure increased to 14.2 %, for I h = 50 % using a polymer of 30 kDa, compared to 4.5 % for pure glass. The modulus of toughness (U T ) increased from 0.73 (pure glass) to 2.64 GPa. Although, the hybrid synthesised in this report did not contain calcium, pTMSPMA/SiO 2 hybrid was found to nucleate bone-like mineral on its surface after 1 week of immersion in simulated body fluid (SBF), whereas pure silica sol-gel glass did not. This increase in apatite forming ability was due to the ion-dipole complexation of calcium with the ester moieties of the polymer that were exposed after release of soluble silica from TEOS. No adverse cytotoxicity for MC3T3-E1 osteoblast-like cells was detected and improved cell attachment was observed, compared to a pure silica gel. pTMSPMA/SiO 2 hybrids have potential for the regeneration of hard tissue as they overcome the major drawbacks of pure inorganic substrates while retaining cell attachment.Bone is the second most transplanted tissue after blood and musculoskeletal pathology treatments represent £10 billion per year in the U.K. alone. 1,2 Effective alternatives must be found to the current methods of skeletal defect treatments to avoid postoperation infection or revision, which can cost up to £70,000 per patient. 3 One attractive approach is to design biodegradable implants that could actively promote the bone growth and tissue remodelling by stimulating cellular activities whilst providing a mechanical support to the tissue. 4 Bioglass R (BG), a biodegradable bioactive silicate glass (46.1 mol % SiO 2 , 26.9 mol % CaO, 24.2 mol % Na 2 O, 2.6 mol % P 2 O 5 ), was the first material capable of bonding with bone by the formation of an apatite layer that forms on its surface after grafting. 5 A second mode of action is its dissolution products (in particular silica), which enhance osteoblast activities, whilst promoting extra- * Corresponding author, E-mail: julian.r.jones@imperial.ac cellular matrix (ECM) production and cells differentiation. 6-8 3D scaffolds have been produced from bioactive glasses, with interconnected pore networks in the form of foams 9,10 or 3-D printed structures 11 , which can take load in compression, up to 150 MPa when 3D printed. 12 ...

Synthesis of cubic spherosilicates for self-assembled organic–inorganic biohybrids based on functionalized methacrylates

“…Such systems are called class II hybrids and can be prepared by carrying out conventional condensation, polymerization, or sol-gel reactions, allowing for the attachment of organic groups onto inorganic materials. [5][6][7] Many successful examples that illustrate countless possibilities of POSS modification have already been described. For instance, Nischang studied tailor-made hybrid organic-inorganic materials based on POSSs by means of thiolene 'click' chemistry.…”

“…13 The construction of methacrylateand acrylate-functionalized POSSs and the characterization of the relationship between chemical structures and physical properties were studied by Ervithayasuporn et al 14 It should be emphasized that interest in methacrylate-based materials has recently increased again, as they are interesting to many research groups in the field of biomaterials. 6,7,[14][15][16][17][18] In this work, we have developed an efficient synthetic approach to hexahedral cage-like organic-inorganic siloxane core biohybrids containing side chains fully functionalized by methacrylate groups derived from monomers such as 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA). Covalent networks created by modified cubic spherosilicates can mimic potential macroporous hybrid biomaterials.…”

Biodegradable inorganic-organic hybrids of methacrylate star polymers for bone regeneration

“…poly (3-(trimethoxysilyl)propyl methacrylate), polyTMSPMA, or poly(MMA-co-TMSPMA). Hybrids produced using polyTMSPMA showed improved ductility [21]. Further improvement was achieved using the copolymer poly(MMA-co-TMSPMA) and the effect of different methacrylate polymer architectures on mechanical properties of the hybrids was investigated [22].…”

Effect of Comonomers on Physical Properties and Cell Attachment to Silica‐Methacrylate/Acrylate Hybrids for Bone Substitution

“…Homopolymers of 3‐(trimethoxysilyl)propyl methacrylate (TMSPMA), a monomer containing alkoxysilane group, have been synthesized and fabricated to poly(TMSPMA)‐SiO 2 hybrids. The hybrids have shown covalent bonding between the polymer and silica network, hydroxycarbonate apatite (HCA) formation was observed during simulated body fluid tests, and osteoblast precursor cell attachment was evident . However, hybrids were still too brittle since every repeating monomer unit had an alkoxysilane group, causing high crosslinking density.…”

“…shown covalent bonding between the polymer and silica network, [22] hydroxycarbonate apatite (HCA) formation was observed during simulated body fluid tests, and osteoblast precursor cell attachment was evident. [23] However, hybrids were still too brittle since every repeating monomer unit had an alkoxysilane group, causing high crosslinking density. Copolymers of MMA and TMSPMA have been investigated as hybrids for bone substitution, and conetwork formation was achieved without phase separation.…”