Publications

2021

2020

Chee, Grace, Trevor Cobb, Katarina Richter-Lunn, Irmandy Wicaksono, and Benjamin R. Freedman. 2020. “Doze: Hydrogel-Based Epidermal Platform for Personalized Scent Diffusion”. Adjunct Proceedings of the 2020 ACM International Joint Conference on Pervasive and Ubiquitous Computing and Proceedings of the 2020 ACM International Symposium on Wearable Computers. New York, NY, USA: Association for Computing Machinery. https://doi.org/10.1145/3410530.3414407.

Doze is an on-skin, hydrogel-based sleep mask which seeks to improve, enhance, and augment sleep through the use of programmed scent diffusion in tune with the user's cortical rhythms. Taking advantage of hydrogels' unique properties, the Doze mask encapsulates and emits therapeutic scents at a regulated pace. The release of scent is controlled by an embedded heater within the layers of the mask and communicates remotely to a smart device. This communication allows for a personalized dosage release based on the user's biometric or contextual data. Investigating both the pervasive power of smell in enhancing sleep as well as natural topical remedies, this personalized mask explores the potential for unintrusive solutions to the evergrowing rarity of a good night's sleep.

Cerebrospinal fluid (CSF) leaks complicate up to 30% of skull base operations. Current surgical adhesives for CSF leak repair are limited by poor adhesion in dynamic and aqueous environments and an inability to reconstruct large cranial defects that span multiple types of tissue. In contrast, tough adhesives are a novel hydrogel coated with an adhesive bridging polymer that provides high performance as a sealant within biological fluids. This novel technology demonstrates extraordinary mechanical toughness, capacity to repeatedly withstand significant strain, and the ability to bind strongly to wet surfaces. However, their application to dural tissue has not been investigated. The purpose of this study was to investigate the use of this novel biomaterial for dural reconstruction and CSF leak prevention. We hypothesized that tough adhesives will exhibit a greater burst pressure compared with existing commercial sealants.

2019

Blacklow, S. O., J. Li, B. R. Freedman, M. Zeidi, C. Chen, and D. J. Mooney. 2019. “Bioinspired Mechanically Active Adhesive Dressings to Accelerate Wound Closure”. Science Advances 5 (7): eaaw3963. https://doi.org/10.1126/sciadv.aaw3963.

Inspired by embryonic wound closure, we present mechanically active dressings to accelerate wound healing. Conventional dressings passively aid healing by maintaining moisture at wound sites. Recent developments have focused on drug and cell delivery to drive a healing process, but these methods are often complicated by drug side effects, sophisticated fabrication, and high cost. Here, we present novel active adhesive dressings consisting of thermoresponsive tough adhesive hydrogels that combine high stretchability, toughness, tissue adhesion, and antimicrobial function. They adhere strongly to the skin and actively contract wounds, in response to exposure to the skin temperature. In vitro and in vivo studies demonstrate their efficacy in accelerating and supporting skin wound healing. Finite element models validate and refine the wound contraction process enabled by these active adhesive dressings. This mechanobiological approach opens new avenues for wound management and may find broad utility in applications ranging from regenerative medicine to soft robotics.

Zuskov, Andrey, Benjamin R. Freedman, Joshua A. Gordon, Joseph J. Sarver, Mark R. Buckley, and Louis J. Soslowsky. 2019. “Tendon Biomechanics and Crimp Properties Following Fatigue Loading Are Influenced by Tendon Type and Age in Mice”. Journal of Orthopaedic Research 38 (1): 36-42. https://doi.org/https://doi.org/10.1002/jor.24407.

In tendon, type-I collagen assembles together into fibrils, fibers, and fascicles that exhibit a wavy or crimped pattern that uncrimps with applied tensile loading. This structural property has been observed across multiple tendons throughout aging and may play an important role in tendon viscoelasticity, response to fatigue loading, healing, and development. Previous work has shown that crimp is permanently altered with the application of fatigue loading. This opens the possibility of evaluating tendon crimp as a clinical surrogate of tissue damage. The purpose of this study was to determine how fatigue loading in tendon affects crimp and mechanical properties throughout aging and between tendon types. Mouse patellar tendons (PT) and flexor digitorum longus (FDL) tendons were fatigue loaded while an integrated plane polariscope simultaneously assessed crimp properties at P150 and P570 days of age to model mature and aged tendon phenotypes (N = 10–11/group). Tendon type, fatigue loading, and aging were found to differentially affect tendon mechanical and crimp properties. FDL tendons had higher modulus and hysteresis, whereas the PT showed more laxity and toe region strain throughout aging. Crimp frequency was consistently higher in FDL compared with PT throughout fatigue loading, whereas the crimp amplitude was cycle dependent. This differential response based on tendon type and age further suggests that the FDL and the PT respond differently to fatigue loading and that this response is age-dependent. Together, our findings suggest that the mechanical and structural effects of fatigue loading are specific to tendon type and age in mice. 

Freedman, Benjamin R., and David J. Mooney. 2019. “Biomaterials to Mimic and Heal Connective Tissues”. Advanced Materials 31 (19): 1806695. https://doi.org/https://doi.org/10.1002/adma.201806695.

Connective tissue is one of the four major types of animal tissue and plays essential roles throughout the human body. Genetic factors, aging, and trauma all contribute to connective tissue dysfunction and motivate the need for strategies to promote healing and regeneration. The goal here is to link a fundamental understanding of connective tissues and their multiscale properties to better inform the design and translation of novel biomaterials to promote their regeneration. Major clinical problems in adipose tissue, cartilage, dermis, and tendon are discussed that inspire the need to replace native connective tissue with biomaterials. Then, multiscale structure–function relationships in native soft connective tissues that may be used to guide material design are detailed. Several biomaterials strategies to improve healing of these tissues that incorporate biologics and are biologic-free are reviewed. Finally, important guidance documents and standards (ASTM, FDA, and EMA) that are important to consider for translating new biomaterials into clinical practice are highligted.

Hillin, Cody D., George W. Fryhofer, Benjamin R. Freedman, Daniel S. Choi, Stephanie N. Weiss, Julianne Huegel, and Louis J. Soslowsky. 2019. “Effects of Immobilization Angle on Tendon Healing After Achilles Rupture in a Rat Model”. Journal of Orthopaedic Research 37 (3): 562-73. https://doi.org/https://doi.org/10.1002/jor.24241.

Conservative (non-operative) treatment of Achilles tendon ruptures is a common alternative to operative treatment. Following rupture, ankle immobilization in plantarflexion is thought to aid healing by restoring tendon end-to-end apposition. However, early activity may improve limb function, challenging the role of immobilization position on tendon healing, as it may affect loading across the injury site. This study investigated the effects of ankle immobilization angle in a rat model of Achilles tendon rupture. We hypothesized that manipulating the ankle from full plantarflexion into a more dorsiflexed position during the immobilization period would result in superior hindlimb function and tendon properties, but that prolonged casting in dorsiflexion would result in inferior outcomes. After Achilles tendon transection, animals were randomized into eight immobilization groups ranging from full plantarflexion (160°) to mid-point (90°) to full dorsiflexion (20°), with or without angle manipulation. Tendon properties and ankle function were influenced by ankle immobilization position and time. Tendon lengthening occurred after 1 week at 20° compared to more plantarflexed angles, and was associated with loss of propulsion force. Dorsiflexing the ankle during immobilization from 160° to 90° produced a stiffer, more aligned tendon, but did not lead to functional changes compared to immobilization at 160°. Although more dorsiflexed immobilization can enhance tissue properties and function of healing Achilles tendon following rupture, full dorsiflexion creates significant tendon elongation regardless of application time. This study suggests that the use of moderate plantarflexion and earlier return to activity can provide improved clinical outcomes.