Novel Continuous Laboratory Reactor with Selectively Tempered Capillary for Hyaluronic Acid Depolymerization: Design, Optimization, and Proof-of-Concept

Hyaluronic acid (HA), a natural polymer produced through biotechnological processes, is initially synthesized with a high molecular weight, which is subsequently reduced for specific applications. This work aims to develop an experimental laboratory device that enables the controlled depolymerization of HA to achieve a targeted molecular weight. This is accomplished by applying precisely regulated temperature and pressure conditions that facilitate the cleavage of HA polymer chains as they pass through a narrow capillary. The process also allows for a controlled exposure time to elevate the temperature and pressure, with the rapid transition between standard and elevated conditions ensuring temporal stability. A key innovation of this approach is the selective application of an elevated temperature to a designated capillary section, adjustable from 0.5 to 5 m in 0.5 m increments, allowing for a broad range of reaction times. Numerical simulations verified temperature distribution along the capillary during heating and cooling. The device’s effectiveness is demonstrated by cleaving HA chains (initial Mw = 2150 kDa) dissolved in an aqueous solution at a 0.1 mg/mL concentration. Results from a factorial experiment that evaluated the extremes of three main variables show cleavage across a wide molecular weight range, reaching values as low as 8 kDa, with a variance of less than 5%. This study presents a viable device for the selective depolymerization of HA via physical parameters alone, eliminating the need for additional substances such as acids, hydroxides, or enzymes.