Lu Fan, Zlobina Ksenia, Baniya Prabhat, Li Houpu, Rondoni Nicholas, Asefifeyzabadi Narges, Hee Wan Shen, Tebyani Maryam, Schorger Kaelan, Franco Celeste, Bagood Michelle, Teodorescu Mircea, Rolandi Marco, Isseroff Rivkah, Gomez Marcella
Applied Mathematics, Baskin Engineering, University of California Santa Cruz, Santa Cruz, CA 95060, USA.
Electrical and Computer Engineering, Baskin Engineering, University of California Santa Cruz, Santa Cruz, CA 95060, USA.
Bioengineering (Basel). 2025 Jul 11;12(7):756. doi: 10.3390/bioengineering12070756.
Advancements in bioelectronic sensors and actuators have paved the way for real-time monitoring and control of the progression of wound healing. Real-time monitoring allows for precise adjustment of treatment strategies to align them with an individual's unique biological response. However, due to the complexities of human-drug interactions and a lack of predictive models, it is challenging to determine how one should adjust drug dosage to achieve the desired biological response. This work proposes an adaptive closed-loop control framework that integrates deep learning, optimal control, and reinforcement learning to update treatment strategies in real time, with the goal of accelerating wound closure. The proposed approach eliminates the need for mathematical modeling of complex nonlinear wound-healing dynamics. We demonstrate the convergence of the controller via an in silico experimental setup, where the proposed approach successfully accelerated the wound-healing process by 17.71%. Finally, we share the experimental setup and results of an in vivo implementation to highlight the translational potential of our work. Our data-driven model suggests that the treatment strategy, as determined by our deep reinforcement learning algorithm, results in an accelerated onset of inflammation and subsequent transition to proliferation in a porcine wound model.
生物电子传感器和致动器的进步为伤口愈合进程的实时监测和控制铺平了道路。实时监测能够精确调整治疗策略,使其与个体独特的生物学反应相匹配。然而,由于人体与药物相互作用的复杂性以及缺乏预测模型,确定如何调整药物剂量以实现期望的生物学反应具有挑战性。这项工作提出了一种自适应闭环控制框架,该框架集成了深度学习、最优控制和强化学习,以实时更新治疗策略,目标是加速伤口闭合。所提出的方法无需对复杂的非线性伤口愈合动力学进行数学建模。我们通过计算机模拟实验装置证明了控制器的收敛性,在该实验中,所提出的方法成功地将伤口愈合过程加速了17.71%。最后,我们分享了体内实验的设置和结果,以突出我们工作的转化潜力。我们的数据驱动模型表明,由我们的深度强化学习算法确定的治疗策略在猪伤口模型中导致炎症的加速发作以及随后向增殖阶段的转变。