In vivo live 3D printing of regenerative bone healing scaffolds for rapid fracture healing
Bio-Inks and methods of using compositions comprising the bio-Inks are disclosed. 3-D tissue repair and regeneration through precise and specific formation of biodegradable tissue scaffolds in a tissue site using the bio-inks are also provided. Specific methylacrylated gelatin hydrogels (MAC) and methacrylated chitosan (MACh) preparations formulated with sucrose, a silicate-containing component (such as laponite), and/or a cross-linking agent (such as a photo-initiator or chemical initiator), as well as powdered preparations of these, are also disclosed. Kits containing these preparations are provided for point-of-care tissue repair in vivo. Superior, more complete (up to 99.85% tissue regeneration within 4 weeks applied in situ), and rapid in situ tissue repair and bone formation are also demonstrated.
1. A method for providing tissue repair in vivo comprising;
combining a first preparation comprising a freeze-dried preparation of a MAG or MACh material with a second preparation comprising sucrose, a silicate based nanoparticle material, and a biocompatible, non-toxic cross-linking agent, to provide a pharmacologically acceptable extrudable composition;
applying the extrudable preparation to a defined tissue region having a defined in vivo target area of soft tissue or bone tissue deficiency in an animal;
exposing the pharmaceutical composition in the defined in vivo target area to a physiologically acceptable wavelength and intensity of ultra violet light for a period of time sufficient to promote polymer cross-linking and formation of filaments; and
providing tissue repair to the defined in vivo target area in the animal.
2. The method of claim 1 wherein the in vivo target area is a bone fracture.
3. The method of claim 1 wherein the biocompatible, non-toxic cross-linking agent is 2-hydroxy-1-(4-(hydroxyethoxy) phenyl) 2-methyl-1-propanone.
4. The method of claim 2 wherein the physiologically acceptable wavelength of ultraviolet light is a 365 nm UV light illumination at an intensity of up to 50 mW/sq. cm.
5. The method of claim 1 wherein the extrudable preparation is applied in a defined series of more than one layer to provide a mesh configuration over the defined in vivo target area.
6. The method of claim 4 wherein the extrudable preparation comprises about 1% to about 20% wt. of methacrylated gelatin (MAG) or methacrylated chitosan (MACh), about 2% to about 8% silicate-based nanoparticles, and about 5% to about 20% sucrose.