In Situ Printing of Adhesive Hydrogel Scaffolds for the Treatment of Skeletal Muscle Injuries.

Reconstructive surgery remains inadequate for the treatment of volumetric muscle loss (VML). The geometry of skeletal muscle defects in VML injuries varies on a case-by-case basis. Three-dimensional (3D) printing has emerged as one strategy that enables the fabrication of scaffolds that match the geometry of the defect site. However, the time and facilities needed for imaging the defect site, processing to render computer models, and printing a suitable scaffold prevent immediate reconstructive interventions post-traumatic injuries. In addition, the proper implantation of hydrogel-based scaffolds, which have generated promising results in vitro, is a major challenge. To overcome these challenges, a paradigm is proposed in which gelatin-based hydrogels are printed directly into the defect area and cross-linked in situ. The adhesiveness of the bioink hydrogel to the skeletal muscles was assessed ex vivo. The suitability of the in situ printed bioink for the delivery of cells is successfully assessed in vitro. Acellular scaffolds are directly printed into the defect site of mice with VML injury, exhibiting proper adhesion to the surrounding tissue and promoting remnant skeletal muscle hypertrophy. The developed handheld printer capable of 3D in situ printing of adhesive scaffolds is a paradigm shift in the rapid yet precise filling of complex skeletal muscle tissue defects.

[1]  H. Vandenburgh,et al.  Minimally invasive approach to the repair of injured skeletal muscle with a shape-memory scaffold. , 2014, Molecular therapy : the journal of the American Society of Gene Therapy.

[2]  Olivier Tassy,et al.  Differentiation of pluripotent stem cells to muscle fiber to model Duchenne muscular dystrophy , 2015, Nature Biotechnology.

[3]  Olivier Pourquié,et al.  Generation of human muscle fibers and satellite-like cells from human pluripotent stem cells in vitro , 2016, Nature Protocols.

[4]  Wonhye Lee,et al.  Bio-printing of collagen and VEGF-releasing fibrin gel scaffolds for neural stem cell culture , 2010, Experimental Neurology.

[5]  Ali Khademhosseini,et al.  Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels , 2012, Advanced functional materials.

[6]  A. Khademhosseini,et al.  Cell-laden microengineered gelatin methacrylate hydrogels. , 2010, Biomaterials.

[7]  C. Fan,et al.  Functional reconstruction of traumatic loss of flexors in forearm with gastrocnemius myocutaneous flap transfer , 2008, Microsurgery.

[8]  Ali Khademhosseini,et al.  3D‐Printed Sugar‐Based Stents Facilitating Vascular Anastomosis , 2018, Advanced healthcare materials.

[9]  B. Sicari,et al.  A murine model of volumetric muscle loss and a regenerative medicine approach for tissue replacement. , 2012, Tissue engineering. Part A.

[10]  J. Hsu,et al.  Volumetric Muscle Loss , 2011, The Journal of the American Academy of Orthopaedic Surgeons.

[11]  K. Gundersen,et al.  Increased hypertrophic response with increased mechanical load in skeletal muscles receiving identical activity patterns. , 2016, American journal of physiology. Cell physiology.

[12]  R. Guldberg,et al.  Functional analysis of limb recovery following autograft treatment of volumetric muscle loss in the quadriceps femoris. , 2014, Journal of biomechanics.

[13]  Yong Xu,et al.  The role of endothelial cells in myofiber differentiation and the vascularization and innervation of bioengineered muscle tissue in vivo. , 2013, Biomaterials.

[14]  S. Fu,et al.  Elastic Modulus of Muscle and Tendon with Shear Wave Ultrasound Elastography: Variations with Different Technical Settings , 2012, PloS one.

[15]  Y. S. Zhang,et al.  Laterally Confined Microfluidic Patterning of Cells for Engineering Spatially Defined Vascularization. , 2016, Small.

[16]  J. Mehta,et al.  Sequentially-crosslinked bioactive hydrogels as nano-patterned substrates with customizable stiffness and degradation for corneal tissue engineering applications. , 2017, Biomaterials.

[17]  S. Ostrovidov,et al.  Enhanced skeletal muscle formation on microfluidic spun gelatin methacryloyl (GelMA) fibres using surface patterning and agrin treatment , 2018, Journal of tissue engineering and regenerative medicine.

[18]  Brian Derby,et al.  Printing and Prototyping of Tissues and Scaffolds , 2012, Science.

[19]  Ali Khademhosseini,et al.  Patient‐Specific Bioinks for 3D Bioprinting of Tissue Engineering Scaffolds , 2018, Advanced healthcare materials.

[20]  Ali Khademhosseini,et al.  Hydrogel Templates for Rapid Manufacturing of Bioactive Fibers and 3D Constructs , 2015, Advanced healthcare materials.

[21]  G. Giatsidis,et al.  Gene expression profiling of skeletal muscle after volumetric muscle loss , 2017, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[22]  Ok Joo Lee,et al.  Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing , 2018, Nature Communications.

[23]  D. Mooney,et al.  Growth factor delivery-based tissue engineering: general approaches and a review of recent developments , 2011, Journal of The Royal Society Interface.

[24]  Seung-Schik Yoo,et al.  Generation of Multi-scale Vascular Network System Within 3D Hydrogel Using 3D Bio-printing Technology , 2014, Cellular and molecular bioengineering.

[25]  Peter Pivonka,et al.  Handheld Co-Axial Bioprinting: Application to in situ surgical cartilage repair , 2017, Scientific Reports.

[26]  Gordon G Wallace,et al.  Development of the Biopen: a handheld device for surgical printing of adipose stem cells at a chondral wound site , 2016, Biofabrication.

[27]  B. Schoenfeld,et al.  A Critical Evaluation of the Biological Construct Skeletal Muscle Hypertrophy: Size Matters but So Does the Measurement , 2019, Front. Physiol..

[28]  Qian Wang,et al.  In vivo passive mechanical properties of skeletal muscle improve with massage-like loading following eccentric exercise. , 2012, Journal of biomechanics.

[29]  G. Pins,et al.  Biomimetic scaffolds for regeneration of volumetric muscle loss in skeletal muscle injuries. , 2015, Acta biomaterialia.

[30]  Tao Xu,et al.  In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds , 2019, Scientific Reports.

[31]  C. Rathbone,et al.  Transplantation of devitalized muscle scaffolds is insufficient for appreciable de novo muscle fiber regeneration after volumetric muscle loss injury , 2014, Cell and Tissue Research.

[32]  Wei Zhu,et al.  Biomimetic 3D-printed scaffolds for spinal cord injury repair , 2019, Nature Medicine.

[33]  Nasim Annabi,et al.  Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing. , 2017, Biomaterials.

[34]  K. Shakesheff,et al.  Growth factor release from tissue engineering scaffolds , 2001, The Journal of pharmacy and pharmacology.

[35]  M Gelinsky,et al.  A definition of bioinks and their distinction from biomaterial inks , 2018, Biofabrication.

[36]  L. Bertassoni,et al.  Photopolymerization of cell-laden gelatin methacryloyl hydrogels using a dental curing light for regenerative dentistry. , 2018, Dental materials : official publication of the Academy of Dental Materials.

[37]  Carlo Reggiani,et al.  Fiber types in mammalian skeletal muscles. , 2011, Physiological reviews.

[38]  A. Khademhosseini,et al.  Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels , 2019, Science Advances.

[39]  Catherine L. Ward,et al.  An Autologous Muscle Tissue Expansion Approach for the Treatment of Volumetric Muscle Loss , 2015, BioResearch open access.

[40]  A. Khademhosseini,et al.  Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. , 2015, Biomaterials.

[41]  Ali Khademhosseini,et al.  3D Bioprinting in Skeletal Muscle Tissue Engineering. , 2019, Small.

[42]  Ali Khademhosseini,et al.  Textile Processes for Engineering Tissues with Biomimetic Architectures and Properties. , 2016, Trends in biotechnology.

[43]  Ali Khademhosseini,et al.  Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue , 2017, Advanced healthcare materials.

[44]  Anthony Atala,et al.  Engineering Complex Tissues , 2012, Science Translational Medicine.

[45]  C. Aguilar,et al.  Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury , 2018, Cell death discovery.

[46]  B. E. Pollot,et al.  Volumetric Muscle Loss. , 2016, Methods in molecular biology.