Joseph W. Freeman
· Professor, Graduate Program DirectorVerifiedRutgers University · Cellular, Molecular and Biomedical Sciences
Active 1959–2025
About
Joseph W. Freeman, Ph.D., is a Professor and Graduate Program Director in the Department of Biomedical Engineering at Rutgers University. He earned his B.S.E. in Chemical Engineering from Princeton University and his Ph.D. in Biomedical Engineering from Rutgers University and The University of Medicine and Dentistry of New Jersey. His doctoral research, conducted in the laboratory of Dr. Frederick H. Silver, focused on type I collagen mineralization and its effects on elastic and viscoelastic properties, as well as tendon development, collagen structure and mechanics, and skin mechanical properties. Following his Ph.D., Dr. Freeman worked as a Research Associate at the University of Virginia in the Department of Orthopaedic Surgery under Dr. Cato T. Laurencin. His research there involved the use of novel biomaterials for bone regeneration, development of scaffolds for ligament repair, hydrogels for ligament repair, and the design of a braiding machine for ligament graft construction. His research interests include the development of new biomaterials for tissue engineering, construction of functional scaffolds for musculoskeletal tissue repair, and molecular modeling of collagen structure and function. At Rutgers, he is actively developing implantable scaffolds for musculoskeletal tissue regeneration, investigating mechanisms of tissue damage and healing, and exploring tumor engineering models. His work emphasizes tissue repair and regeneration through tissue engineering techniques, with a focus on musculoskeletal tissues.
Research topics
- Materials science
- Chemistry
- Biomedical engineering
- Anatomy
- Medicine
- Composite material
- Organic chemistry
- Biochemistry
- Cell biology
- Engineering
- Biology
- Surgery
- Biophysics
- Pathology
- Nuclear chemistry
- Polymer chemistry
- Nanotechnology
- Internal medicine
- Traditional medicine
Selected publications
Regenerative Engineering and Translational Medicine · 2025-04-03
articleOpen accessSenior authorAbstract Purpose To identify novel fertilized egg yolk–derived compounds that enhance myoblast differentiation, we used a myosin light chain (MLC) luciferase C2C12 reporter cell line to quantify myotube formation, an indicator of myoblast differentiation, in response to adding three different fractions: granule, lipid, and aqueous. Methods A C2C12 MLC-luciferase reporter myoblast cell line was cultured in media supplemented with three different egg yolk–derived fractions. Cellular assays and fluorescence imaging were conducted to determine the viability, morphology, and myotube formation in response to the egg yolk fraction additives. Fertilized and unfertilized egg yolk fractions were examined for their protein MW profile to determine if there were differences in the protein populations. Results None of the fractions had a negative effect on cellular viability measured on days 0, 3, 7, and 10. Two fractions showed increased differentiation compared to the null control (1%): the granule and the lipid. Comparison of the MW profiles of the fractions confirmed differences in protein populations between them with apo-LDLs, apo-HDLs, and phosvitin being the major bands present in the granule and lipid groups. No differences in protein profiles were observed between the fertilized and unfertilized groups. Conclusion Granule- and lipid-fertilized egg yolk–derived fractions show potential for use as differentiating agents for myotube formation in C2C12 myoblasts supporting their nutritional value for treatment of sarcopenia or to enhance myoblast differentiation for tissue engineering. Lay Summary Sarcopenia or muscle wasting is a prevalent problem in the elderly population which leads to increased healthcare costs. We have separated fertilized egg yolk into fractions to test their potential to increase muscle formation by adding them to muscle progenitor cells. Some of these fractions show great potential for increase differentiation of muscle tissue in treatment of sarcopenia or for muscle tissue engineering.
Regenerative Engineering and Translational Medicine · 2024-12-04 · 4 citations
articleOpen accessSenior authorAbstract Purpose Trauma, injury, disease, infection, congenital deformities, and non-union after a fracture can lead to significant loss of bone tissue resulting in large bone defects. If left untreated, this can lead to decreased bone strength, stability, and function as well as long-term malformations. We present a novel, pre-vascularized 3D-printed biodegradable scaffold mimicking the architecture of native bone as a bone graft alternative to promote vascularized bone regeneration. Methods Scaffolds with a highly porous central trabecular section surrounded by an outer cortical section modeled after the bone’s osteons were 3D printed in polylactic acid (PLA). Hydroxyapatite (HA) posts were incorporated to improve mechanical strength. A soak-freeze technique was used to introduce additional porosity to support the recruitment, proliferation, and differentiation of stem cells. Scaffolds were mineralized to provide cues for osteoconduction and osteoinduction. They were also pre-vascularized to promote the differentiation of stem cells along the vascular lineage. Results Compression mechanical testing showed the addition of HA posts improved mechanical strength. Using the soak-freeze technique, micropores in the range of 0–10 µm were introduced. Osteogenic differentiation capability of the scaffolds was verified in vitro through the estimation of osteocalcin (OC) produced by the cells seeded on them and by staining for alkaline phosphatase. Differentiation of stem cells along the vascular lineage within the scaffold was confirmed via the estimation of vascular endothelial growth factor (VEGF-A) and by staining for CD31, a marker for vascular differentiation. Conclusion This novel scaffold incorporated with cues necessary to promote the regeneration of bone and its vasculature shows promise as an alternative to currently used bone grafts. Lay Summary Significant bone loss caused by trauma, infection, or disease results in large defects that are currently treated using bone grafts—autografts (taken from the same patient), allografts and xenografts (donor tissue), or synthetic grafts. We have developed a tissue-engineered alternative that mimics the architecture of natural bone and has cues to promote both the regeneration of bone and its vasculature. These are fabricated using 3D printing (3DP) technology, providing cost-effective, customizable alternatives to conventional bone grafts.
Tissue Engineered 3D Constructs for Volumetric Muscle Loss
Annals of Biomedical Engineering · 2024-07-31 · 22 citations
reviewOpen accessSenior authorSevere injuries to skeletal muscles, including cases of volumetric muscle loss (VML), are linked to substantial tissue damage, resulting in functional impairment and lasting disability. While skeletal muscle can regenerate following minor damage, extensive tissue loss in VML disrupts the natural regenerative capacity of the affected muscle tissue. Existing clinical approaches for VML, such as soft-tissue reconstruction and advanced bracing methods, need to be revised to restore tissue function and are associated with limitations in tissue availability and donor-site complications. Advancements in tissue engineering (TE), particularly in scaffold design and the delivery of cells and growth factors, show promising potential for regenerating damaged skeletal muscle tissue and restoring function. This article provides a brief overview of the pathophysiology of VML and critiques the shortcomings of current treatments. The subsequent section focuses on the criteria for designing TE scaffolds, offering insights into various natural and synthetic biomaterials and cell types for effectively regenerating skeletal muscle. We also review multiple TE strategies involving both acellular and cellular scaffolds to encourage the development and maturation of muscle tissue and facilitate integration, vascularization, and innervation. Finally, the article explores technical challenges hindering successful translation into clinical applications.
Rational design of poly(peptide-ester) block copolymers for enzyme-specific surface resorption
Journal of Materials Chemistry B · 2023-01-01 · 8 citations
articleOpen accessCorrespondingTissue resorption and remodeling are pivotal steps in successful healing and regeneration, and it is important to design biomaterials that are responsive to regenerative processes in native tissue. The cell types responsible for remodeling, such as macrophages in the soft tissue wound environment and osteoclasts in the bone environment, utilize a class of enzymes called proteases to degrade the organic matrix. Many hydrophobic thermoplastics used in tissue regeneration are designed to degrade and resorb passively through hydrolytic mechanisms, leaving the potential of proteolytic-guided degradation underutilized. Here, we report the design and synthesis of a tyrosol-derived peptide-polyester block copolymer where protease-mediated resorption is tuned through changing the chemistry of the base polymer backbone and protease specificity is imparted through incorporation of specific peptide sequences. Quartz crystal microbalance was used to quantify polymer surface resorption upon exposure to various enzymes. Aqueous solubility of the diacids and the thermal properties of the resulting polymer had a significant effect on enzyme-mediated polymer resorption. While peptide incorporation at 2 mol% had little effect on the final thermal and physical properties of the block copolymers, its incorporation improved polymer resorption significantly in a peptide sequence- and protease-specific manner. To our knowledge, this is the first example of a peptide-incorporated linear thermoplastic with protease-specific sensitivity reported in the literature. The product is a modular system for engineering specificity in how polyesters can resorb under physiological conditions, thus providing a potential framework for improving vascularization and integration of biomaterials used in tissue engineering.
Regenerative Engineering and Translational Medicine · 2023-05-25 · 4 citations
articleSenior authorBiomicrofluidics · 2023-03-01 · 7 citations
articleOpen accessTissue regeneration-promoting and drug-eluting biomaterials are commonly implanted into animals as a part of late-stage testing before committing to human trials required by the government. Because the trials are very expensive (e.g., they can cost over a billion U.S. dollars), it is critical for companies to have the best possible characterization of the materials' safety and efficacy before it goes into a human. However, the conventional approaches to biomaterial evaluation necessitate sacrificial analysis (i.e., euthanizing a different animal for measuring each time point and retrieving the implant for histological analysis), due to the inability to monitor how the host tissues respond to the presence of the material in situ. This is expensive, inaccurate, discontinuous, and unethical. In contrast, our manuscript presents a novel microfluidic platform potentially capable of performing non-disruptive fluid manipulations within the spatial constraints of an 8 mm diameter critical calvarial defect—a “gold standard” model for testing engineered bone tissue scaffolds in living animals. In particular, here, addressable microfluidic plumbing is specifically adapted for the in vivo implantation into a simulated rat's skull, and is integrated with a combinatorial multiplexer for a better scaling of many time points and/or biological signal measurements. The collected samples (modeled as food dyes for proof of concept) are then transported, stored, and analyzed ex vivo, which adds previously-unavailable ease and flexibility. Furthermore, care is taken to maintain a fluid equilibrium in the simulated animal's head during the sampling to avoid damage to the host and to the implant. Ultimately, future implantation protocols and technology improvements are envisioned toward the end of the manuscript. Although the bone tissue engineering application was chosen as a proof of concept, with further work, the technology is potentially versatile enough for other in vivo sampling applications. Hence, the successful outcomes of its advancement should benefit companies developing, testing, and producing vaccines and drugs by accelerating the translation of advanced cell culturing tech to the clinical market. Moreover, the nondestructive monitoring of the in vivo environment can lower animal experiment costs and provide data-gathering continuity superior to the conventional destructive analysis. Lastly, the reduction of sacrifices stemming from the use of this technology would make future animal experiments more ethical.
Annals of Biomedical Engineering · 2023 · 6 citations
Senior authorCorresponding- Biophysics
- Chemistry
- Biomedical engineering
PLoS ONE · 2022 · 11 citations
- Medicine
- Biomedical engineering
- Anatomy
Osteoarthritis and rheumatoid arthritis are debilitating conditions, affecting millions of people. Both osteoarthritis and rheumatoid arthritis degrade the articular cartilage (AC) at the ends of long bones, resulting in weakened tissue prone to further damage. This degradation impairs the cartilage's mechanical properties leading to areas of thinned cartilage and exposed bone which compromises the integrity of the joint. No preventative measures exist for joint destruction. Discovering a way to slow the degradation of AC or prevent it would slow the painful progression of the disease, allowing millions to live pain-free. Recently, that the articular injection of the polyphenol epigallocatechin-gallate (EGCG) slows AC damage in an arthritis rat model. It was suggested that EGCG crosslinks AC and makes it resistant to degradation. However, direct evidence that intraarticular injection of EGCG crosslinks cartilage collagen and changes its compressive properties are not known. The aim of this study was to investigate the effects of intraarticular injection of EGCG induced biomechanical properties of AC. We hypothesize that in vivo exposure EGCG will bind and crosslink to AC collagen and alter its biomechanical properties. We developed a technique of nano-indentation to investigate articular cartilage properties by measuring cartilage compressive properties and quantifying differences due to EGCG exposure. In this study, the rat knee joint was subjected to a series of intraarticular injections of EGCG and contralateral knee joint was injected with saline. After the injections animals were sacrificed, and the knees were removed and tested in an anatomically relevant model of nanoindentation. All mechanical data was normalized to the measurements in the contralateral knee to better compare data between the animals. The data demonstrated significant increases for reduced elastic modulus (57.5%), hardness (83.2%), and stiffness (17.6%) in cartilage treated with injections of EGCG normalized to those treated with just saline solution when compared to baseline subjects without injections, with a significance level of alpha = 0.05. This data provides evidence that EGCG treated cartilage yields a strengthened cartilage matrix as compared to AC from the saline injected knees. These findings are significant because the increase in cartilage biomechanics will translate into resistance to degradation in arthritis. Furthermore, the data suggest for the first time that it is possible to strengthen the articular cartilage by intraarticular injections of polyphenols. Although this data is preliminary, it suggests that clinical applications of EGCG treated cartilage could yield strengthened tissue with the potential to resist or compensate for matrix degradation caused by arthritis.
Regenerative Engineering and Translational Medicine · 2022
Senior authorCorresponding- Materials science
- Biomedical engineering
- Composite material
<scp>Self‐actuating</scp> multilayer scaffold for skeletal muscle tissue engineering
Polymers for Advanced Technologies · 2022-07-03 · 5 citations
articleOpen accessSenior authorCorrespondingAbstract Electroactive polymers (EAP) can alter and change their shape when subjected to an electric field, they have been investigated for a variety of purposes including smart drug delivery and artificial muscles. However, approaches to design electroactive hydrogel structures can be hindered by low polymeric conductivity, which then requires high electrical input to induce movement and results in low cellular viability. Our purpose in this study, was to reduce the input voltage required for movement by layering electroactive PEGDA:Acrylic acid (PEGDA:AA) with poly(ethylene glycol) diacrylate (PEGDA) modified with a conductive nanocomposite of colloidal poly(3,4 ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) and graphene oxide (GO). In this study PEDOT:PSS/GO was a flexible electrode that stimulated the PEGDA:AA. The multilayered hydrogel was evaluated for angular movement, electrical properties, and biocompatibility with C2C12 myoblast cells. The data showed that increasing the PEDOT:PSS/GO in the hydrogel decreased the conductivity, potentially due to the presence of GO. The addition of PEDOT:PSS/GO increased scaffold movement compared with PEGDA:AA alone when stimulated at 1 V. Fewer scaffolds displayed significantly more movement with increased voltage, but the 10% PEDOT:PSS/GO group experienced more movement at each tested voltage. C2C12 cells on the 10% PEDOT:PSS/GO were more metabolically active than cells on scaffolds with increased concentrations of PEDOT:PSS/GO. This work is an initial step in creating biocompatible scaffolds capable of actuation for tissue engineering.
Recent grants
NIH · $344k · 2015
Microelectronically Stimulating and Actuating Nanofibers for Muscle Replacement and Regeneration
NSF · $328k · 2014–2018
NSF · $206k · 2010–2012
BRIGE: The Fabrication of a Novel, Full Thickness, Artificial Bone Graft for Bone Tissue Engineering
NSF · $202k · 2009–2011
NSF · $205k · 2011–2014
Frequent coauthors
- 16 shared
Kristin M. Fischer
Hampden–Sydney College
- 16 shared
Emmanuel C. Ekwueme
Harvard University
- 15 shared
Albert L. Kwansa
North Carolina State University
- 14 shared
Daniel P. Browe
Rutgers, The State University of New Jersey
- 14 shared
Brittany Taylor
University of Florida
- 14 shared
Marissa Nichole Rylander
Walker (United States)
- 14 shared
Frederick H. Silver
Rutgers, The State University of New Jersey
- 14 shared
Cato T. Laurencin
California Institute for Regenerative Medicine
Labs
Musculoskeletal Tissue Regeneration LaboratoryPI
Education
Other, Chemical Engineering
Princeton University
Ph.D., Biomedical Engineering
Rutgers University and The University of Medicine and Dentistry of New Jersey
Awards & honors
- Ford Foundation Fellow
- NIH Training Program Fellow
- Johnson & Johnson Graduate Fellow
- NIH Interdisciplinary Biotechnology Ph.D. Training Program F…
- New Jersey Center-Whitaker for Biomaterials Fellow
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