As minimally invasive surgical techniques progress, the demand for reliable ligation is pronounced. The surgical advantages of energy-based vessel sealing exceed those of traditional, compression-based ligatures in procedures sensitive to duration, foreign bodies, and recovery time alike. While the use of energy-based devices to seal or transect vasculature and connective tissue bundles is widespread, the breadth of heating strategies and energy dosimetry used between devices underscores an uncertainty as to the molecular nature of the sealing mechanism and induced tissue bond. Further, energy-based techniques (e.g., tissue “fusion” or tissue “welding”) exhibit promise for the closure, repair and functional recovery of soft and connective tissues in the orthopaedic, colorectal and dermal domains. To optimize and progress the use of energy-based tissue fusion, a constitutive theory of molecular bonding forces that arise in response to supraphysiological temperatures is required. While rapid tissue bonding may arise from dehydration and water transport, dipole interactions, covalent crosslinks or the coagulation of cellular proteins, long-term tissue repair requires that the reaction to thermal damage be tailored to accelerate and mimic the onset of biological healing and remodeling. The aim of this work is to supplement the findings of published thermal fusion research by exploring the contributions of primary and secondary tissue constituents to the formation of energy-based fusion bonds. Results of this work and their associated implications to the theory of energy-based surgical adhesion will encourage a molecular approach to characterization of the prevalent and promising energy-based tissue bond.