Benjamin Freedman

Benjamin Freedman
Harvard University | Harvard · Wyss Institute for Biologically Inspired Engineering

PhD, Bioengineering

About

79
Publications
13,389
Reads
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1,592
Citations
Citations since 2017
32 Research Items
1382 Citations
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20172018201920202021202220230100200300
20172018201920202021202220230100200300
20172018201920202021202220230100200300
Additional affiliations
September 2011 - present
University of Pennsylvania
Position
  • PhD Student
June 2011 - August 2011
National Institutes of Health
Position
  • Intramural Research Training Award (IRTA)
June 2010 - August 2011
National Institutes of Health
Position
  • INTRAMURAL RESEARCH TRAINING AWARD

Publications

Publications (79)
Article
This review highlights recent research on Achilles tendon healing, and comments on the current clinical controversy surrounding the diagnosis and treatment of injury. The processes of Achilles tendon healing, as demonstrated through changes in its structure, composition, and biomechanics, are reviewed. Finally, a review of tendon developmental biol...
Article
Full-text available
Background: Achilles tendon ruptures are traumatic injuries, and techniques for assessing repair outcomes rely on patient-based measures of pain and function, which do not directly assess tendon healing. Consequently, there is a need for a quantitative, in vivo measure of tendon properties. Method of Approach: Therefore, the purpose of this study w...
Article
Achilles tendon injuries affect both athletes and the general population, and their incidence is rising. In particular, the Achilles tendon is subject to dynamic loading at or near failure loads during activity, and fatigue induced damage is likely a contributing factor to ultimate tendon failure. Unfortunately, little is known about how injured Ac...
Article
Full-text available
Multicellular spheroids made of stem cells can act as building blocks that fuse to capture complex aspects of native in vivo environments, but the effect of hydrogel viscoelasticity on cell migration from spheroids and their fusion remains largely unknown. Here, we investigated the effect of viscoelasticity on migration and fusion behavior of mesen...
Preprint
Lymph nodes (LNs) dynamically expand in response to immunization, but the relationship between LN expansion and the accompanying adaptive immune response is unclear. Here, we first characterized the LN response across time and length scales to vaccines of distinct strengths. High-frequency ultrasound revealed that a bolus ‘weak’ vaccine induced a s...
Article
Hydrogel-based drug delivery systems typically aim to release drugs locally to tissue in an extended manner. Tissue adhesive alginate-polyacrylamide tough hydrogels were recently demonstrated to serve as an extended-release system for the corticosteroid triamcinolone acetonide. Here, we describe the stimuli-responsive controlled release of triamcin...
Article
Full-text available
Approved therapies for tendon diseases have not yet changed the clinical practice of symptomatic pain treatment and physiotherapy. This review article summarizes advances in the development of novel drugs, biologic products, and biomaterial therapies for tendon diseases with perspectives for translation of integrated therapies. Shifting from target...
Article
Full-text available
Tissue adhesives capable of achieving strong and tough adhesion in permeable wet environments are useful in many biomedical applications. However, adhesion generated through covalent bond formation directly with the functional groups of tissues (i.e., ‐COOH and ‐NH2 groups in collagen), or using non‐covalent interactions can both be limited by weak...
Article
Full-text available
Aging is the largest risk factor for Achilles tendon associated disorders and rupture. Although Achilles tendon macroscale elastic properties are suggested to decline with aging, less is known about the effect of maturity and aging on multiscale viscoelastic properties and their effect on tendon cell behavior. Here, we show dose dependent changes i...
Article
Full-text available
Hydrogels that provide mechanical support and sustainably release therapeutics have been used to treat tendon injuries. However, most hydrogels are insufficiently tough, release drugs in bursts, and require cell infiltration or suturing to integrate with surrounding tissue. Here we report that a hydrogel serving as a high-capacity drug depot and co...
Article
Operative treatment is assumed to provide superior outcomes to non-operative (conservative) treatment following Achilles tendon rupture, however, this remains controversial. This study explores the effect of surgical repair on Achilles tendon healing. Rat Achilles tendons (n=101) were bluntly transected and were randomized into groups receiving rep...
Article
Full-text available
Mechanical stimulation (mechanotherapy) can promote skeletal muscle repair, but a lack of reproducible protocols and mechanistic understanding of the relation between mechanical cues and tissue regeneration limit progress in this field. To address these gaps, we developed a robotic device equipped with real-time force control and compatible with ul...
Article
Tendinopathy is a debilitating disease that causes as much as 30% of all musculoskeletal consultations. Existing treatments for tendinopathy have variable efficacy, possibly due to incomplete characterization of the underlying pathophysiology. Mechanical load can have both beneficial and detrimental effects on tendon, as the overall tendon response...
Article
Full-text available
The development of tough adhesive hydrogels has enabled unprecedented adhesion to wet and moving tissue surfaces throughout the body, but they are typically composed of nondegradable components. Here, a family of degradable tough adhesive hydrogels containing ≈90% water by incorporating covalently networked degradable crosslinkers and hydrolyzable...
Article
Background/purpose We sought to test select properties of a novel, expandable bioadhesive composite that allows for enhanced adhesion control in liquid environments. Methods Rabbit fetuses (n = 23) underwent surgical creation of spina bifida on gestational day 22–25 (term 32–33 days). Defects were immediately covered with a two-component tough adh...
Data
The PDF file includes: Fig. S1. Antimicrobial tests. Fig. S2. Histological sections on day 3 specimens. Fig. S3. Finite element simulation. Table S1. Material parameters used in finite element stimulation. Table S2. Comparison of mechanical and antimicrobial properties of materials related to wound care.
Data
Finite element simulation of AAD-enabled wound contraction.
Article
Full-text available
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, sophistic...
Article
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, tendon healing...
Article
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...
Article
Sex differences in the mechanical properties of different musculoskeletal tissues and their impact on tendon function and disease are becoming increasingly recognized. Tendon mechanical properties are influenced by the presence or absence of sex hormones and these effects appear to be tendon- or ligament-specific. The objective of this study was to...
Article
Full-text available
The extracellular matrix (ECM) is the primary biomechanical environment that interacts with tendon cells (tenocytes). Stresses applied via muscle contraction during skeletal movement transfer across structural hierarchies to the tenocyte nucleus in native uninjured tendons. Alterations to ECM structural and mechanical properties due to mechanical l...
Article
Full-text available
Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low drug loading capacity, deficiencies in mechanical toughness and storage stability, and poor control over the drug release that often results in burst release and short release duration. This work reports a design of composite clay h...
Article
A covalently crosslinked methacrylated (MA)-alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA-algi...
Article
Tendon experiences a variety of multiscale changes to its extracellular matrix during mechanical loading at the fascicle, fibre and fibril levels. For example, tensile loading of tendon increases its stiffness, with organization of collagen fibres, and increases cell strain in the direction of loading. Although applied macroscale strains correlate...
Article
Spontaneous rupture of the Achilles tendon is increasingly common in the middle aged population. However, the cause for the particularly high incidence of injury in this age group is not well understood. Therefore, the objective of this study was to identify age-specific differences in the Achilles tendon-muscle complex using an animal model. Funct...
Article
Conservative treatment (non-operative) of Achilles tendon ruptures is suggested to produce equivalent capacity for return to function; however, long term results and the role of return to activity (RTA) for this treatment paradigm remain unclear. Therefore, the objective of this study was to evaluate the long term response of conservatively treated...
Article
Introduction: Achilles tendon ruptures affect 15 of 100,000 women and 55 of 100,000 men each year. Controversy continues to exist regarding optimal treatment and rehabilitation protocols. The objective of this study was to investigate the temporal effects of surgical repair and immobilization or activity on Achilles tendon healing and limb functio...
Article
The extracellular matrix (ECM) is a major component of the biomechanical environment with which tendon cells (tenocytes) interact. Alterations to matrix structural and mechanical properties due to mechanical loading may promote normal tendon homeostasis or create pathological conditions. For example, fatigue loading of tendon elevates collagen fibe...
Article
Achilles tendon ruptures are common injuries. Sex differences are present in mechanical properties of uninjured Achilles tendon, but it remains unknown if these differences extend to tendon healing. We hypothesized that ovariectomized females (OVX) and males would exhibit inferior post-injury tendon properties compared to females. Male, female, and...
Article
The Achilles tendon is the most commonly ruptured tendon in the human body. Numerous studies have reported incidence of these injuries to be upwards of five times as common in men than women. Therefore, the objective of this study was to investigate the sex- and hormone-specific differences between Achilles tendon and muscle between female, ovariec...
Article
Achilles tendon ruptures are common and devastating injuries; however, an optimized treatment and rehabilitation protocol has yet to be defined. Therefore, the objective of this study was to investigate the effects of surgical repair and return to activity on joint function and Achilles tendon properties after 3-weeks of healing. Sprague Dawley rat...
Article
Gait analysis is a quantitative, non-invasive technique that can be used to investigate functional changes in animal models of musculoskeletal disease. Changes in ground reaction forces following injury have been observed that coincide with differences in tissue mechanical and histological properties during healing. However, measurement of these ki...
Article
Full-text available
Several factors are believed to contribute to patellofemoral joint function throughout knee flexion including patellofemoral (PF) kinematics, contact, and bone morphology. However, data evaluating the PF joint in this highly flexed state have been limited. Therefore, the purpose of this study was to evaluate patellofemoral contact and alignment in...
Article
As tendons are loaded, they reduce in volume and exude fluid to the surrounding medium. Experimental studies have shown that tendon stretching results in a Poisson's ratio greater than 0.5, with a maximum value at small strains followed by a nonlinear decay. Here we present a computational model that attributes this macroscopic observation to the m...
Article
The extracellular matrix (ECM) is a major component of the biomechanical environment with which cells interact, and it plays important roles in both normal development and disease progression. Mechanical and biochemical factors alter the biomechanical properties of tissues by driving cellular remodeling of the ECM. This review provides an overview...
Article
Patients with classic (type I) Ehlers-Danlos Syndrome (EDS), characterized by heterozygous mutations in the Col5a1 and Col5a2 genes, exhibit connective tissue hyperelasticity and recurrent joint dislocations, indicating a potential regulatory role for collagen V in joint stabilizing soft tissues. This study asked whether the contribution of collage...
Article
Full-text available
Collagen V mutations underlie classic Ehlers-Danlos syndrome, and joint hypermobility is a significant clinical manifestation. We define the function of collagen V in tendons and ligaments, as well as the role of alterations in collagen V expression in the pathobiology in classic Ehlers-Danlos syndrome. A conditional Col5a1(flox/flox) mouse model w...
Article
The complex structure of tendons relates to their mechanical properties. Previous research has associated the waviness of collagen fibers (crimp) during quasi-static tensile loading to tensile mechanics, but less is known about the role of fatigue loading on crimp properties. In this study (IACUC approved), mouse patellar tendons were fatigue loade...
Article
Full-text available
Background The Q-angle is widely used clinically to evaluate individuals with anterior knee pain. Recent studies have questioned the utility of this measure and have suggested that a large Q-angle may not be associated with lateral patellofemoral translation, as often assumed. The objective of this study was to determine: 1) how accurately the Q-an...
Article
Full-text available
Patellofemoral pain syndrome causes significant discomfort and disability among much of the general population. Despite recent breakthroughs in dynamic three-dimensional imaging technologies to assess pathological patellofemoral motion, such tools remain costly for clinical diagnostics applications. Thus, this study investigated whether three-dimen...
Conference Paper
There is little known about how vibration loading affects the biomechanical and physiological response of tissues of the spine, especially the ligaments. This study investigated the effects of whole body vibration (WBV) on the thoracic facet capsular ligaments using a rat model of vibration. Ligaments were tested in tension after a WBV exposure. Th...

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