Executive Summary : | Tailoring the wound healing process in diabetic ulcers and personalised patients' requirement are still unmet clinical challenges. Each patient has a unique wound type based on the lost cells as well as specific layer. However, split thickness autografts, which are current gold standards for wound treatment have failed in larger sized defects due to limited availability of the graft. The complete functionality of skin tissue including cell-cell communications, signal transductions and critical barrier functions with native equivalence cannot be captured using conventional tissue engineering approaches. Recently 3D bioprinting process offers spatial control over the deposition of multiple cell types and growth factors with respect to patient wound and develops the live printed constructs. However, this prefabricated bioprinted construct may not exactly fill the wound site as the skin grafting often requires the prior debridement of the skin tissue. Similarly, the hydrogel-based 3D bioprinted construct may disintegrate during the implantation procedure. Hence, this requires the in vivo bioprinting approach to print cells along with growth promoting substances with spatial hierarchy directly onto the wound site. We hypothesize that such system would enable the surgeons to directly print the epidermal and dermal compartments specific to wound size on wound site. Such device will bring the recapitulating aspects of additive manufacturing process into clinics. The specific aims of the proposal are: (1) Design and development of hand-held Biopen with multiple heads; (2) In vitro demonstration of flexible writing of bioinks using hand-held Biopen; (3) In vivo validation of hand-held Biopen printing performance of different types of wounds including various sizes, shapes and thickness using smaller animal models. In aim #1, hand-held Biopen will be designed to dispense multiple cell types and growth factors as a printed sheets through mono-, co- and tri-axial nozzles. The designed Biopen components will be 3D printed using optically transparent light weight polymeric materials and fixed with the flow-rate controller to control the volume of the bioinks during printing process. In aim #2, epidermal and dermal bioinks will be prepared and flexible writing of multiple bioinks using hand-held Biopen will be demonstrated. These printed hydrogels will be further examined for cell viability, proliferations, spreading, cellular heterogeneity and cell-cell communications both qualitatively and quantitatively. In aim #3, hand-held Biopen will further be validated for its direct printing performance on wounds of various sizes, shapes and thickness using animal models after obtaining institutional animal ethical clearance. Hence, the proposed study stands unique as it integrates 3D bioprinting with a multiple microfluidic cartridges and portability that can enable surgeons to dispense the bioinks with cells precisely with increased surgical sculpting and dexterity. |
Co-PI: | Dr. Dhakshinamoorthy Sundaramurthi, Sastra University, Tamil Nadu-613401, Dr. Anuradha Subramanian, Sastra University, Tamil Nadu,Thirumalaisamudram,Tamil Nadu,Thanjavur-613401 |