Gelatin Porous Scaffolds as Delivery Systems of Calcium Alendronate

Abstract

The systemic administration of bisphosphonates (BPs) for the treatment of metabolic diseases characterized by abnormal bone loss suffers from several adverse side effects, which can be reduced by implementation of alternative modes of administration. In this work, glutaraldehyde cross-linked gelatin scaffolds are proposed as delivery systems of calcium alendronate monohydrate (CaAL•H O). The 3D highly porous scaffolds display a relevant interconnected porosity (>94%), independently from CaAL•H O content (0, 3, and 6 wt%). At variance, pore size varies with composition. The relative increase of the number of smaller pores on increasing BP content is in agreement with the parallel significant increase of the compressive modulus and collapse strength. The scaffolds exhibit a sustained CaAL•H O release profile, and a significant amount of the drug is retained in the scaffolds even after 14 d. In vitro tests are carried out using cocultures of osteoblast (OB) and osteoclast (OC). The evaluation of differentiation markers is performed both on the supernatants of cell culture and by means of quantitative polymerase chain reaction. The results indicate that BP containing scaffolds support osteoblast proliferation and differentiation, whereas they inhibit osteoclast viability and activity, displaying a promising beneficial role on bone repair processes.

Strontium‐Substituted Hydroxyapatite‐Gelatin Biomimetic Scaffolds Modulate Bone Cell Response

“…Gelatin-based scaffolds were prepared starting from a 10% w/v aqueous gelatin solution, as described in literature. [30] 30 g of gelatin were dissolved in 300 mL of distilled water at 55 °C, then 13 g of HA or Sr-HA (30% w/w) were added. The suspension was mechanically stirred (≈600 rpm) for about 5 min to obtain white foam.…”

“…As a consequence, gelatin‐based biomaterials must be stabilized against dissolution in solution. To this purpose, we cross‐linked the foamed scaffolds with glutaraldehyde at relatively low concentration, which does not provoke any cytotoxic effect …”

“…To this purpose, we cross-linked the foamed scaffolds with glutaraldehyde at relatively low concentration, which does not provoke any cytotoxic effect. [29,30] Calcium and strontium belong to the same group of the periodic table of elements and exhibit a similar chemical behavior. Thus, it is not surprising that Sr can replace Ca in hydroxyapatite in the whole range of composition.…”

Calcium Phosphates as Delivery Systems for Bisphosphonates

“…Porosity can be obtained using a variety of methods, including gas foaming, freeze drying, electrospinning, and 3D printing [ 101 , 102 ]. Porous scaffolds have been proposed as delivery systems for BPs [ 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. Loading of the drugs can be achieved through adsorption on the pre-formed scaffold, through addition to the bulk structure as scaffold components, as well as via incorporation onto the scaffold of BP loaded liposomes [ 107 , 109 , 110 , 111 ].…”

“…Porous scaffolds have been proposed as delivery systems for BPs [ 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. Loading of the drugs can be achieved through adsorption on the pre-formed scaffold, through addition to the bulk structure as scaffold components, as well as via incorporation onto the scaffold of BP loaded liposomes [ 107 , 109 , 110 , 111 ]. Tarafder and Bose [ 107 ] loaded alendronate on 3D printed interconnected porous tricalcium phosphate (TCP) scaffolds and implanted as prepared scaffolds and polycaprolactone coated scaffolds in the distal femoral defects of Sprague Dawley rats.…”