Biomedical Engineering and Bioengineering Commons^™

Design And Development Of A Perfusable Hydrogel Platform With Bioprinted Human-Endothelialized Microvascular Channels, Calvin A. Chernyatinskiy

All Theses

We developed an integrated bioprinting and perfusion platform to generate vascularized hydrogel constructs that support perfusable microchannel networks. Multiple hydrogel formulations, sacrificial ink systems, device geometries, and perfusion conditions were systematically evaluated to optimize print fidelity, mechanical stability, and cellular compatibility. Internally gelling alginate–calcium carbonate hydrogels were identified as a robust matrix, providing tunable gelation kinetics and structural stability during embedded printing. In parallel, Pluronic F-127 fugitive ink enabled reliable fabrication of continuous hollow channels due to its shear-thinning behavior and efficient post-print removal.

The finalized platform integrates stereolithographically fabricated perfusion chambers with extrusion-based bioprinting to produce three-dimensional, perfusable vascular …

Development Of An Adhesive Emulsion Hydrogel For Soft Tissue Reconstruction, David J. Alpert

Dissertations and Theses

Soft tissue filling materials are most commonly associated with various aesthetic, cosmetic procedures, primarily using lightly cross-linked hyaluronic acid to fill wrinkles and give facial features a more youthful appearance. These natural materials are biocompatible but degrade over time while more persistent synthetic fillers may provoke a chronic inflammatory response. Migration from the injection site is also a key factor as this may not only render the implant non- functional but necessitate further procedures for removal of the foreign material. Such concerns are more pronounced for soft tissue reconstruction procedures (e.g., to treat congenital defects or traumatic injuries), which require …

Imine Crosslinked, Injectable, And Self-Healing Fucoidan Hydrogel With Immunomodulatory Properties, Asma Talib Qureshi, Shajia Afrin, Saad Asim, Muhammad Rizwan

Michigan Tech Publications

Biomaterials with inherent anti-inflammatory properties and the ability to foster a pro-regenerative environment hold significant promise for enhancing cell transplantation and tissue regeneration. Fucoidan, a sulfated polysaccharide with well-documented immune-regulatory and antioxidant capabilities, offers strong potential for creating such biomaterials. Yet, there is a lack of engineered fucoidan hydrogels that are injectable and provide tunable physicochemical properties. In this study, the ability of fucoidan to undergo periodate-mediated oxidation is leveraged to introduce aldehydes into backbone (oxidized fucoidan, OFu), enabling the formation of reversible, imine-crosslinks with amine-containing molecules such as gelatin. The imine-crosslinked OFu-gelatin hydrogel provided excellent control over gelation rate …

Nanofiber-Hydrogel Composite Scaffold Fabrication Methods For Peripheral Nerve Regeneration, Jacob Lee Carter

Theses and Dissertations

Nerve graft conduits (NGCs) are a rapidly advancing field for treating peripheral nerve injuries that aim to guide the growth of regenerating axons across damaged gaps. A more effective NGC can be manufactured by combining the use of nanofibers to act as guidewires within a 3-D hydrogel that imitates the extracellular matrix of nerve tissue. Several methods have been developed to embed aligned nanofibers in an ordered architecture within a hydrogel matrix. The first method involves layer-by-layer additive manufacturing to create NGCs with rows of polycaprolactone (PCL) nanofibers surrounded by a gelatin methacrylate (GelMe) hydrogel in a 3-D structure. A …

Development Of Glutathione-Responsive Disulfide-Containing Poly(Beta-Amino Esters) With Varied Hydrophilicity And Acrylate Functionality, Anastasiia Aronova

Theses and Dissertations--Chemical and Materials Engineering

Smart biomaterials are becoming promising for therapeutic deliveries due to their ability to respond to changes in the environment. Redox-responsive hydrogels are a promising type of smart polymer that can swell and degrade according to cellular oxidative stress levels. Glutathione, abundant in cells, is crucial in redox-responsive biomaterials, serving as a key reactive molecule. This study explored the degradation kinetics of glutathione-responsive poly(β-amino ester) (PBAE) polymers created through a single-step Michael addition. We examined how disulfide content influences the degradation kinetics of these PBAE networks. Additionally, we investigated how the hydrophilicity and functionality of acrylate affect the degradation of disulfide-containing …

Evaluation Of Silk Fibroin And Hylauronic Acid As Otic Drug Delivery System Additives; Investigation Of Silk Fibroins Responses To Enviromental Stimulii, Kolton Charles Sandau

Graduate Student Theses, Dissertations, & Professional Papers

The Serban lab has previously developed and reported on a single application drug delivery system for the treatment of otitis externa. Otitis externa also known as outer ear infections is a very common ailment that impacts large portions of both human and domestic animal populations. Typical treatment for otitis externa typically requires an extended dosing regimen over several days that is inconvenient and can lead to poor clinical outcomes due to poor patient compliance. Our delivery system employs a thixotropic gel to deliver a steady dose of medication over the duration of the infection.

Here we evaluated the reproducibility and …

The Effect Of Phase-Separated Microstructures On Cell Migration In 3d Dextran Hydrogels, Jenifer Sidhwa

Honors Theses and Capstones

No abstract provided.

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Improving Peripheral Nerve Regeneration Through Rehabilitation And Biomaterial-Based Drug Delivery Strategies, Yunfan Kong

Theses & Dissertations

Peripheral nerve injury (PNI) is a common problem worldwide, with trauma being a common cause. PNI can lead to loss of sensory and motor functions, chronic neuropathic pain, and mental health issues, significantly impacting patients' family life, work, and social situation. Recent studies revealed that beyond the topical injury site at peripheral nerves, PNIs can also induce dysfunctions in the central nervous system (CNS) by causing maladaptive plasticity, which will result in exaggeration and exacerbation of the pathological condition caused by primary injuries. The common therapy strategies for PNI treatment are using sutures, nerve autografts or conduits in cases requiring …

Self-Healing Properties Of Augmented Injectable Hydrogels Over Time, Connor Castro, Zachary R. Brown, Erik Brewer

Henry M. Rowan College of Engineering Departmental Research

Injectable polymers offer great benefits compared to other types of implants; however, they tend to suffer from increased mechanical wear and may need a replacement implant to restore these mechanical properties. The purpose of this experiment is to investigate an injectable hydrogel's self-healing ability to augment itself to a previously molded implant. This was accomplished by performing a tensile strength test to examine potential diminishing mechanical properties with increasing time, as well as dye penetration tests to examine the formation of interfacial bonds between healed areas of hydrogels. There were several time points in between injections that were explored, from …

3-Dimensional Muscle Constructs: Using Hydrogels In Order To Model The Effects Of Exercise In Disease Conditions, Mark Mchargue

Theses and Dissertations--Biomedical Engineering

Currently, there is no standard in vitro model for studying the effects of mechanical stimulation on muscle in type II diabetes. Existing models primarily utilize electrical stimulation, which does not fully recapitulate the effects of exercise. In this thesis, we create a standardized in vitro model of murine muscle that can recapitulate the benefits seen in exercise when mechanically stimulated. Moreover, we show that a type II diabetes environment has similar effects on the muscle in vitro as well as in vivo.

Sodium Hyaluronate Based Drug Delivery To The Outer And Inner Ear, Emma Barrett-Catton

Graduate Student Theses, Dissertations, & Professional Papers

We have developed two projects using sodium hyaluronate (HA)-based systems for drug delivery to the ear. First, we investigated an HA-based hydrogel for use as a single use antibiotic treatment for otitis externa. Otitis externa, also known as outer ear infection, is a frequent affliction in both humans and animals. The most prevalent treatment for otitis externa is ear drops, but it is difficult to adhere properly to this treatment, causing poor patient compliance and the potential for complications. As a result, we have developed an HA-based hydrogel for use as a single application treatment for otitis externa to increase …

A Novel Biomaterial Platform For Cardiac Tissue Engineering, Andrew House

Dissertations

Heart disease is one of the leading causes of death in the world. With a growing demand for in vitro cardiac models that can recapitulate the complex physiology of the cardiac tissue, there is a desire to create novel therapies and treatments. However, due to a lack of fundamental understanding of the heart's inflammatory response to myocardial infarction, the development of new therapies is both time consuming and costly. In this work, a novel approach to fabricating a dynamic hydrogel cardiac platform is reported. This platform better mimics the dynamic changes occurring in the native cardiac tissue microenvironment during cardiac …

Leveraging Isocyanate Chemistry For Low Cost And Highly Functional Hydrogels, Henry Beaman

Dissertations - ALL

The development of novel biomaterials is an important step in providing higher quality products for wound healing, drug delivery, and tissue engineering. Progress is consistently being made in the development of new polymers, yet new polymer systems are often expensive and/or involve complex multistep synthesis methods. These limitations could hinder the translation and scalability of functionalized materials. To address the issues of complex synthesis and high cost, we have devised strategies for polymeric modification using isocyanate chemistry. Isocyanates are used in the manufacturing of polyurethanes. Isocyanates are highly reactive with common functional groups, such as amines, hydroxyls, and carboxylic acids. …

Characterization Of Thermal Gelation Properties In Bioresorbable Thermally Activated Hydrogel Polymers For Hernia Surgery Applications, Alexander Mayfield

All Theses

Hydrogel adhesives are a new class of materials with excellent biocompatibility, which makes them very attractive for biomaterial applications. It has been previously shown that Tetronic T1107, a four-arm poly (propylene oxide)-poly (ethylene oxide) (PPO-PEO) block copolymer, is useful as a chemical crosslinking thermo-responsive hydrogel for bioadhesive applications. The end groups of this polymer are modified with acrylate and N-hydroxysuccinimide (NHS) functional groups. The acrylate end group gives the polymer cohesive properties with long-range chemical crosslinking using dithiothreitol (DTT), while the NHS end group gives the polymer adhesive properties through bonding with amines found in organic tissue. It was found …

Development Of A Decellularized Hydrogel Composite And Its Application In A Novel Model Of Disc-Associated Low Back Pain In Female Sprague Dawley Rats, David Lillyman

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Chronic low back pain is a global socioeconomic crisis compounded by an absence of reliable, curative treatments. The predominant pathology associated with chronic low back pain is degeneration of intervertebral discs in the lumbar spine. During degeneration, nerves can sprout into the intervertebral disc tissue and be chronically subjected to inflammatory and mechanical stimuli, resulting in pain. Pain arising from the intervertebral disc, or disc-associated pain, is a complex, multi-faceted disorder which necessitates valid animal models to screen therapeutics and study pathomechanisms of pain.

While many research teams have created animal models of disc degeneration, the translation of these platforms …

Design Of Self-Assembled Peptides For Wound Healing, Ka-Kyung Kim

Dissertations

According to the CDC, 15% of diabetic patients develop diabetic foot ulcers (DFU) and approximately 170,000 patients undergo non-traumatic amputation annually. DFU is a major complication of diabetes caused by non-healing full-thickness wounds through the dermis. The current treatments include blood sugar control, frequent debridement, offloading, moist wound care, infection treatment, and amputation. To achieve wound closure of DFU, appropriate wound care and antibiotic therapy are essential. Topical regimens include hydrocolloids, alginates, foam, silver-impregnated dressings, and hydrogels. Wound healing is a complex and dynamic interplay between the immune system, keratinocytes, and dermal cells (in case of cutaneous wound). Angiogenesis has …

Synthesis Of Thiol-Acrylate Hydrogels For 3d Cell Culture And Microfluidic Applications, Anowar Hossain Khan

LSU Doctoral Dissertations

Globally cell culture is an $18.98 billion industry as of 2020, with an 11.6 percent annual growth rate. Drug discovery has an estimated worth of $69.8 billion in 2020 and is predicted to grow to $110.4 billion by 2025. Three-dimensional (3D) cell culture of cancer cells is one of the rapidly growing felids since it better recapitulates in vivo conditions compared to two-dimensional (2D) models. However, it is challenging to grow 3D tumor spheroids outside the body, and some of the existing technology can generate these spheroids outside the human body but poorly mimic in vivo tumor models. Therefore, there …

Optimization Of A Novel Nipam-Based Thermoresponsive Copolymer For Intramuscular Injection As A Myoblast Delivery Vehicle To Combat Peripheral Artery Occlusive Disease, Quentin R. Klueter

Master's Theses

There is a need for a minimally invasive delivery method to enable cell therapies to combat peripheral artery occlusive disease (PAOD) in end stage patients. Myoblasts show promise as a cell mediated therapy but warrant an improved delivery method to increase cell retention in the region of interest because of their adherent nature, relative to previously used BM-MNC’s that are non-adherent. Contemporary issues with achieving successful cell therapies of vasculature can be mainly characterized by the lack of clinical translation from promising animal studies and absence of cell delivery scaffolding. Naturally, polymers have been widely experimented with as grafts to …

Novel Stimuli-Responsive Pectin-Pvp-Functionalized Clay Based Smart Hydrogels For Drug Delivery And Controlled Release Application, Shabnam Rehmat, Nayab Batool Rizvi, Saba Urooge Khan, Abdul Ghaffar, Atif Islam, Rafi Ullah Khan, Azra Mehmood, Hira Butt, Muhammad Rizwan

Michigan Tech Publications, Part 1

Stimuli-responsive drug delivery systems are urgently required for injectable site-specific delivery and release of drugs in a controlled manner. For this purpose, we developed novel pH-sensitive, biodegradable, and antimicrobial hydrogels from bio-macromolecule pectin, polyvinylpyrrolidone (PVP), 3-aminopropyl (diethoxy)methyl silane (3-APDEMS), and sepiolite clay via blending and solution casting technique. The purified sepiolite (40 um) was functionalized with 3-APDEMS crosslinker (ex-situ modification) followed by hydrogels fabrication. FTIR and SEM confirmed crosslinked structural integrity and rod-like morphology of hydrogels respectively. The swelling properties of hydrogels could be controlled by varying the concentration of modified clay in pectin/PVP blends. Moreover, the decrease in pH …

Mesenchymal Stromal Cell And Chondrocyte Mobility In 3d Bioprinted Hydrogel Constructs, Alesia Lokshina

Honors Undergraduate Theses

Osteoarthritis (OA) is a progressive cartilage degeneration disease with a complex pathologic mechanism. Although OA has devastating effects on patient quality of life and places a significant burden on the healthcare system, no disease-modifying drugs have been found, and surgical treatment options are often unsustainable. 3D bioprinting is a novel field within tissue engineering that focuses on developing biocompatible constructs that can be implanted to replace an organ or tissue. Such constructs have a great potential to become treatments for OA. Understanding cell mobility within hydrogels could play a vital role in advancing the development of biocompatible constructs. However, due …

Development Of Cellulose-Based, Semi-Interpenetrating Network Hydrogels As Tissue-Adhesive, Thermoresponsive, Injectable Implants, Jesse Martin

Dissertations and Theses

Abstract Development of Cellulose-Based, Semi-Interpenetrating Network Hydrogels as Tissue-Adhesive, Thermoresponsive, Injectable Implants

Hydrogels are three-dimensional polymer networks with high water content and tunable mechanical properties, which have been widely investigated as replacements for soft tissues, such as the intervertebral disc (IVD). Various derivatives of the plant polysaccharide, cellulose, have been explored for use as injectable hydrogel implants. Methylcellulose (MC), which exhibits thermogelation at temperatures above 32°C, and relatively hydrophilic carboxymethyl-cellulose (CMC), are versatile cellulosic polymers that have shown promise as base materials for such applications. In prior work, functionalization with methacrylate groups allowed for the formation of stable, covalently crosslinked …

Development And Characterization Of A Decellularized Neuroinhibitory Scaffold Containing Matrix Bound Nanovesicles, Logan Piening

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Chronic low back pain (LBP) is a leading cause of disability but treatments for LBP are limited. Degeneration of the intervertebral disc leads to loss of neuroinhibitory sulfated glycosaminoglycans (sGAGs) which allows nerves from dorsal root ganglia (DRG) to grow into the core of the disc, leading to pain. Current treatments for LBP involve drugs that do not target the source of the pain and lack long term efficacy or use invasive surgeries with high complication rates. Treatment with a decellularized tissue scaffold that contains neuroinhibitory components may inhibit nerve growth and prevent disc-associated LBP. Here, a decellularized nucleus pulposus …

Controlled Release Of Multiple Therapeutics From Silicone Hydrogel Contact Lenses For Post-Cataract/Post-Refractive Surgery And Uveitis Treatment., Stephen A Dipasquale, Biaggio Uricoli, Matthew C Dicerbo, Thea L Brown, Mark Byrne

Henry M. Rowan College of Engineering Departmental Research

PURPOSE: This work demonstrates seven-day controlled and extended in vitro physiological flow dual release of multiple post-ocular surgery therapeutics from extended-wear contact lenses as a dropless alternative for treatment of uveitis and corneal inflammation, pain, and infection. Lens replacement each week optimizes treatment matching patient recall time with the ability to increase or decrease dosage.

METHODS: Lenses were synthesized using molecular imprinting to create lenses with macromolecular memory for diclofenac sodium (DS) and dexamethasone sodium phosphate (DMSP), as well as bromfenac sodium (BS) and moxifloxacin (MOX). Drug uptake and release were analyzed, and physical properties were measured and compared to …

Poly(2-Hydroxyethyl Methacrylate) Hydrogels For Contact Lens Applications–A Review, Kushendarsyah Saptaji, Nurlaely Rohmatul Iza, Sinta Widianingrum, Vania Katherine Mulia, Iwan Setiawan

Makara Journal of Science

The emerging technology in biomedical engineering requires biocompatible materials, which are also referred to as biomaterials. For a material to be considered biocompatible, it should not interact with human tissues in a harmful way, and vice versa. Various properties of biocompatible materials, such as mechanical and optical properties, have to be considered for different biomedical applications. One of the most popular applications of biomaterials is for contact lenses. Hydrogels, specifically poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels, are among the most popular ones in ophthalmologic applications, especially in soft contact lenses. This paper reviews the use of PHEMA hydrogels as one of the …

Localized Treatment Of Malignant Melanoma Using A Modified Cellulose-Based Hydrogel Loaded With Temozolomide With Increased Safety Of Human Dermal Fibroblasts And The Mechanisms Behind The Effect, Joseph Wolf

Bioengineering Dissertations - Archive

Melanoma pathophysiology is highly varied, and the initial cause of tumorigenesis is still unknown, but it is likely a combination of both epigenetic and genetic means. Further, melanoma tumors have one of the highest mutational burdens of all cancers and are largely composed of varied subpopulations within the same tumor. These two factors provide insight into why melanoma is so difficult to treat medicinally. Dacarbazine is the gold-standard of metastatic melanoma treatment, yet only has an overall response rate of 22% and no impact on survival. Temozolomide (TMZ), an analog of dacarbazine, is often viewed as a more ideal choice …

Silk Hydrogels Incorporated With Melanin, Anne Lutz

Browse all Theses and Dissertations

Melanin is a naturally produced pigment found within the human body. Melanin is known for its ability to protect against Ultra Violet light, but also its ability to allow for mechanical protection. Making melanin a good addition to biomedical devices such as hydrogels. Silk hydrogels are weak in their load bearing capabilities but are known for their biocompatibility, biodegradability, and porosity. This makes the silk hydrogel a good material to incorporate melanin into in order to improve the mechanical properties. For the silk solution to form a solid, there must be a presence of both a catalyst and an oxidizer …

Injectable Gelatin-Silk Fibroin Composite Hydrogels For In Situ Cell Encapsulation, Ryann D. Boudreau

Honors Theses and Capstones

Hydrogels are widely used tools for tissue engineering and regenerative medicine. Characterized as biofunctional, water-based polymer matrices with tunable mechanical properties, hydrogels have promising but limited applications in biomedical engineering, due to poor and static matrix strength. Here we plan to rectify this issue by introducing a new hydrogel made from a composite of gelatin and silk fibroin crosslinked by microbial transglutaminase (mTG) instantly and beta sheet formation gradually, respectively. This interpenetrating network (IPN) shows enhanced mechanical stiffness and strength compared to gelatin hydrogels, and is capable of encapsulating human cells with high viability demonstrated by the encapsulation of human …

Development Of Novel Inks And Approaches For Printing Tissues And Organs, Shen Ji

Dissertations

Tissue engineering is a multidisciplinary field that investigates and develops new methods to repair, regenerate and replace damaged tissues and organs, or to develop biomaterial platforms as in vitro models. Tissue engineering approaches require the fabrication of scaffolds using biomaterials or fabrication of living tissues using cells. As the demands of customized, implantable tissue/organs are increasing and becoming more urgent, conventional scaffold fabrication approaches are difficult to meet the requirements, especially for complex large-scale tissue fabrication. In this regard, three-dimensional (3D) printing attracted more interest over the past decades due to its unrivaled ability to fabricate highly customized tissues or …

Small Molecule Drug Release Form In Situ Forming Degradable Scaffolds Incorporating Hydrogels And Bioceramic Microparticles, David A. Puleo, Todd A. Milbrandt, J. Zach Hilt, Paul Fisher, Vishwas Talwalkar

Biomedical Engineering Faculty Patents

The present invention relates to an injectable system combining a hydrogel, a bioceramic and a degradable matrix that provides for sustained drug delivery and structural support to recovering tissue, such as bone and the periodontium.