R-3 Repository :: Browsing by Author "Hartgerink, Jeffrey D"

Browsing by Author "Hartgerink, Jeffrey D"

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All-Conjugated Block Copolymers for Organic Photovoltaic Applications
(2014-12-03) Smith, Kendall Allen; Verduzco, Rafael; Chapman, Walter G; Hartgerink, Jeffrey D
Conventional inorganic solar technologies are expensive due to the high cost of processing, while organic materials have significant cost advantages in the raw materials and ease of processing. Unfortunately, organic devices suffer from low efficiency due to difficulty in transporting charges to the electrodes. Typical devices mix the donor and acceptor components and anneal them to allow for phase separation. However, because the phase separation is uncontrolled, domains may be larger than optimal and isolated domains can be formed reducing efficiency. All-conjugated block copolymers have the potential to improve efficiency by creating an ordered structure with controlled domains and continuous pathways through self-assembly. In this work, the relationships between structure, optoelectronic properties, and processing conditions for these materials are systematically investigated using two routes to obtain the materials. In one route, functionalized catalysts are used to initiate controlled polymerizations of two different polymers. These well functionalized precursors are then joined together using copper catalyzed azide alkyne click chemistry. In a second route, a sequential polymerization route is employed where one polymer is synthesized with a well-defined end-group. The polymer is then used as a macroreagent to end-cap a Suzuki polycondensation reaction, yielding materials with direct conjugation between the blocks. The first route yields well-defined materials, whereas the second can access a broader variety of polymers. For all these materials, processing conditions are varied and the morphology of the all-conjugated block copolymers are analyzed by a combination of grazing-incidence X-ray scattering, neutron scattering and reflectivity, atomic force microscopy, and transmission electron microscopy. Materials are found to self-assemble into thermodynamically stable structures with well-defined length scales. It is found that crystallization of either block is predominant in all block copolymers studied, but at intermediate ratios crystallization of both blocks is observed. Processing conditions such as casting temperature, annealing duration, and speed of quenching to room temperature are found to have important effects on thin film crystallinity and orientation of the π-π stacking direction of polymer crystallites. By varying the annealing duration and quenching speed, crystallization of either or both block can be obtained.
Design and Synthesis of Biologically Relevant Collagen Mimetic Peptides
(2022-04-18) Hulgan, Sarah Annette Hahn; Hartgerink, Jeffrey D
The triple helix is a unique and important protein fold present in the collagen family of proteins, a large family of extracellular matrix proteins abundant in the human body. Collagen mimetic peptides (CMPs) are currently of great utility for studying the structure and biological functions of the collagen triple helix. Chapter 1 is a review of recent advances in the field of collagen mimetic peptide design with an overview of CMPs in structural, biological, and biomaterial applications. Chapter 2 will discuss pairwise amino acid interactions studied in a methodical manner for deconvoluting the stability each interaction contributes to the triple helix. This study both increased our understanding of the collagen triple helix structure as well as contributed to the training set for an algorithm which predicts the stability and specificity of triple helices with great accuracy for natural amino acids. This algorithm allows one to utilize pairwise interactions to design heterotrimers with predictable stability and specificity of assembly. Chapter 3 presents covalent capture methodology as a means for stabilizing CMP triple helices. This method uses the pairwise interactions K-D and K-E studied in Chapter 1 to first direct helix assembly, followed by amide bond formation to cross-link the helix. Covalent capture removes the problematic monomer to trimer equilibrium that causes slow folding rates, mixtures of triple helix compositions, and limits in vivo applications of CMPs. Applications of CMPs is next explored, by studying protein interactions with collagen and designing collagen targeting peptides. Chapter 4 utilizes covalent capture to limit the degradation of a CMP by matrix metalloproteinas-1 (MMP-1). Covalent capture limits the rotational movement of the individual CMP peptide strands; therefore, comparison of this covalently captured to a supramolecular peptide gives valuable insight into the collagenolytic mechanism of MMPs. Additionally, development of a peptide with limited degradation by MMPs would be of utility for peptide biomaterial applications. Finally, Chapter 5 will discuss our recent advances towards a collagen targeting peptide (CTP) with specificity for a single collagen type. CTPs have been shown in the literature to be useful for targeting collagen for imaging and drug delivery but with no specificity for collagen type. We design CTPs to target collagen types 1-3 using rational design of pairwise interactions and a scoring function (from Chapter 2) and evaluate these CTP designs via folding with CMPs, binding to extracted natural collagens, and histological staining. CMP helices are of great utility for the continued study of the natural collagen structure and its many protein interactions and diseases. Advances in all these areas have resulted in significant improvements to our understanding and control of this important class of protein.
Design, Structure and Applications of Collagen-Mimetic Peptides
(2017-04-25) Acevedo-Jake, Amanda M; Hartgerink, Jeffrey D; Matsuda, Seiichi P
The collagen triple helix is a unique protein fold found in all domains of life where is has diverse roles from imparting structure and strength to tissue, to initiating an immune response. While many factors affecting the structure and stability of the triple helix have previously been elucidated, much remains unknown about collagen. Using collagen-mimetic peptides, it is possible to investigate the molecular structure of the triple helix, determine new pairwise interactions of amino acids, characterize disease models and also create designer collagens that will preferentially hybridize to natural collagen-rich tissue. First a selective labeling scheme is used to thoroughly characterize a well-folded triple helical region, and then to determine the degree of localized unfolding at the N- and C-termini. Though terminal fraying extends farther than previously shown, small sequence alterations at the N-terminus have a drastic influence on local stability (~15C). Next, a single register heterotrimeric mimic of the type I collagen disease Osteogenesis Imperfecta is used to investigate single point glycine mutations in the B chain, the A chain or both chains. Unlike past reports, a combination of NMR analysis and molecular modelling is used to generate structures of the mutated helices and visualize the underlying mechanisms of helix destabilization in OI. For the first time it is proven that these mutations cause compositional as well as structural disruptions. Additionally, while several hundred pairwise interactions are possible in the triple helix, to date only two interactions are wellunderstood and commonly incorporated into CMP design. To expand on the library of known interactions, the structure and stability of helices containing serine, threonine, phospho-serine and phospho-threonine were investigated. Notably, when phospho-serine is paired with lysine a new highly stabilizing (49.5 C) axial interaction is possible. Finally, the design of a collagen type II targeting peptide is described, and NMR, CD and confocal microscopy are used to investigate the hybridization of the synthetic peptide with the natural partner strands.
Development of Bioactive Collagen Mimetic Peptides (CMPs) Using Supramolecular and Covalent Techniques
(2023-04-20) Peterson, Caroline M; Hartgerink, Jeffrey D
Collagen mimetic peptides (CMPs) are an excellent tool for studying both the structure and function of natural collagen. Total synthetic control of the amino acid sequence allows for the deliberate manipulation of the triple helical structure. The ability to engineer CMPs with structural modifications directly influences the ability to mimic collagen biological function. In Chapter 1 the use of CMPs to model collagen primary, secondary, tertiary and quaternary structures is evaluated. The utility of CMPs to model collagen-receptor interactions and the current uses of CMPs in biomaterials are discussed. The synthesis of highly specific and stable heterotrimeric triple helices is very challenging. Chapter 2 details the principles that guide the design of these peptides. Elements of positive and negative design, including supramolecular charge pairs and single residue substitutions were used in combination with a computational algorithm to obtain a single register and composition ABC heterotrimer. This peptide design was then used as a heterotrimeric template to evaluate the utility of new pairwise interactions. Although supramolecular interactions are a great tool for driving the assembly of the triple helix, frequently it is desirable to form covalent bonds between the strands to increase the stability and fasten the folding of CMPs. Chapter 3 is a detailed study of the covalent capture of CMPs. The effects of the number and placement of isopeptide bonds are evaluated. Also, for the first time the differences between covalently linked frame shifted CMPs are studied. Several trends are identified, which will inform the ideal use of covalent bonds in CMPs. Chapter 4 details a study on how the structure of CMPs directly impacts biological activity. A CMP with the integrin binding motif “GFOGER” is designed and tested for cell adhesion before and after covalent capture. The establishment of covalent bonds between the strands of the triple helix results in increased integrin binding, demonstrating the need for synthetic methods to “lock” the triple helical structure. Chapter 5 describes the efforts to incorporate this integrin binding CMP into two different materials. To functionalize a peptide hydrogel with the CMP, a click chemistry approach is used. The sequence of the CMP was modified with an alkyne, which does not disrupt the tertiary structure. After covalent capture, this CMP can be conjugated to an azide bearing peptide fragment. To functionalize liposomes with the integrin binding CMP, a peptide amphiphile was designed. Despite the presence of the hydrophobic tail, this CMP can still successfully undergo covalent capture. Incorporation of the CMP into these materials may increase their interactions with cells. Finally, in Chapter 6 covalent capture is used to synthesize a library of stabilized peptide mimics of Surfactant Protein A (SP-A). These peptides are screened for cell adhesion, and several important residues are identified. CMPs can successfully mimic the interactions between innate immune proteins and their receptors.
Development of Multidomain Peptide Hydrogels for Tissue Engineering Applications
(2017-04-10) Moore, Amanda Noel; Hartgerink, Jeffrey D
Over the past decade, multidomain peptides (MDP) have been designed, synthesized, and customized for tissue engineering applications. The goals of this work were twofold: 1) to develop novel MDP hydrogels with unique chemical properties 2) to evaluate previously developed MDP hydrogels for biocompatibility. By utilizing the principle of covalent capture, an MDP hydrogel with enhanced rheological properties was developed and characterized. The incorporation of cysteine residues into the MDP sequence allowed for covalent bonding between adjacent peptide nanofibers, which ultimately resulted in a hydrogel with increased rheological properties. Through in vitro, ex vivo, and in vivo experimentation, biological response to several MDP hydrogels was evaluated. This work highlights the immense importance of systemic factors in the physiological response to the MDP. Ex vivo experiments performed on the dental pulp of extracted rat mandibles showed little cellular infiltration, and sequestration of key proteins in the MDP hydrogel was noted. Hydrogels injected near odontoblast cells absorbed dentin sialophosphoprotein, a protein with key applications in regenerative dentistry. When MDP hydrogel was injected into the core of pulpal soft tissue, extracellular matrix deposition, scaffold remodeling, and biodegradation were seen. These results support potential use of the MDP as a scaffold for tissue engineering of the dental pulp. In vivo subcutaneous injection experiments contrasted ex vivo results with rapid cellular infiltration of the MDP hydrogel. The MDP hydrogel quickly becomes highly vascularized, and a high density of nerve fascicles from the peripheral nervous system are found within the MDP implant. A cytokine array elucidated key proteins secreted by cells into the MDP hydrogel that may be responsible for these effects, and it is hypothesized that the immune system plays a significant role in defining these responses. Lastly, an attempt to mimic the function of bone morphogenetic protein-2 (BMP-2) using the MDP hydrogel is described. The BMP-2 mimetic MDP hydrogel demonstrated cytocompatibility with pre-osteoblast cells, but failed to induce ectopic calcification after subcutaneous injection. Through a variety of experiments, including ex vivo, in vitro, and in vivo analysis, advances were made in understanding the physiological response to MDPs and its dependency on MDP sequence.
Multidomain Peptide Biomaterials for Enhanced Delivery of Anti-Cancer Immunotherapies
(2020-04-22) Leach, David Gilbert; Hartgerink, Jeffrey D
In cancer research, it is increasingly clear that standard drug administration strategies are insufficient to resolve advanced disease states. While monotherapies using systemically delivered drugs can effectively treat many classes of diseases, cancer represents a uniquely complex challenge that demands a sophisticated response. One strategy researchers are using combines anti-cancer immunotherapies with biomaterial-based delivery vehicles. Biomaterials, such as preformed implantable scaffolds and injectable soft materials, possess powerful synergies with immunotherapies. Immunotherapies on their own typically have poor delivery properties, and often require repeated high-dose injections that result in serious off-tumor effects and/or limited efficacy. Rationally designed biomaterials can allow for discrete localization and controlled release of immunotherapeutic agents, and have been shown to improve outcomes in the treatment of cancers. In this thesis, we developed biomaterial systems to control the release and presentation of anti-cancer therapeutics, with the goal of overcoming many of the problems limiting cancer immunotherapy. Multidomain peptide (MDP) biomaterials were optimized for localized delivery of both small molecules and biologics, allowing for focused dose concentrations and extended therapy presentation. In the first project, a Stimulator of Interferon Genes (STING) agonist was delivered from a cationic MDP hydrogel via intratumoral injection, showing direct cancer cell cytotoxicity and 6-fold enhanced tumor treatment efficacy compared to STING agonist alone. More advanced formulations were also developed, allowing for co-delivery of STING agonists and checkpoint inhibitor antibodies from a single intratumoral hydrogel injection. In a second project, a drug-mimicking hydrogel was developed as a novel anti-cancer biomaterial without any exogenously loaded factors. Specifically, the hydrogel was designed to mimic a small molecule inhibitor of inducible Nitric Oxide Synthase (iNOS) called N6-(1-iminoethyl)-L-lysine (L-NIL). The ‘L-NIL-MDP’ hydrogel had comparable bioactivity to L-NIL, able to inhibit iNOS and affect tumor biology over an extended period of time. In ongoing work, the L-NIL-MDP was combined with STING agonists and immunotherapeutic antibodies to create a superior second-generation anti-tumor formulation termed SynerGel. Fundamentally, the work described herein expands the toolbox of available biomaterial designs that can be used for enhanced drug delivery applications.
Multidomain Peptide Hydrogels for Transected Nerve Regeneration
(2022-10-20) Lai, Cheuk Sun Edwin; Hartgerink, Jeffrey D; Grande-Allen, K. Jane
Transected peripheral nerve injury (PNI) is caused by traumatic accidents or medical interventions, leading to the loss of motor and sensory functions in patients. While autografts and FDA-approved nerve guidance conduits (NGCs) are partially eﬀective in treating transected PNI, they suﬀer from multiple constraints that confine their use to human nerve defects < 3 cm. Hence, further research is conducted to create bioengineered NGCs that strive for accelerated axonal growth, which correlates to better surgical outcome. Recent tissue engineering strategies consist of neurotrophic factors delivery, stem cell encapsulation, and inner structural support. Multidomain peptide (MDP) hydrogels are of interest due to their extracellular matrix-like architecture and bioactive nature that recapitulate native nerve tissues. In this thesis, the neuroregenerative capability of MDP hydrogels and NGCs was vigorously investigated by bridging 10 mm in vivo rat nerve defects and performing functional characterizations at sacrificial timepoints. In chapter 1, the background information of self-assembling peptide hydrogels was reviewed, followed by the previous and current developments of NGCs. In chapter 2, an electrospun poly(ϵ-caprolactone) (PCL) nerve conduit was successfully developed to hold MDP hydrogels and nerve segments in place. In chapter 3, preliminary in vitro and in vivo studies were conducted to optimize the experimental design and to perform initial evaluation on MDPs. Chapter 4 focuses on assessing the efficacy of cationic and anionic MDP hydrogels in restoring motor and electrical functions after rat sciatic nerve transections. Anionic MDP outperforms its cationic counterpart 16 weeks post operation. In chapter 5, the acrylamidation and nucleobase-conjugation on MDPs were examined with potential application in promoting peripheral nerve regeneration. Despite its poor biocompatibility, photo-responsive peptide material can be created by incorporating acrylamides in cationic MDPs. The research on nucleobase modification remains in progress. Fundamentally, the objective of this research is to determine whether MDP hydrogels, when placed within PCL nerve conduits, can accelerate nerve regeneration after sciatic nerve injury and to explore the additional functionalities of MDPs with two modifications.
Peptide nanostructured materials: Expanding their chemical diversity and understanding their biological activity
(2020-04-21) Lopez Silva, Tania Lizeth; Hartgerink, Jeffrey D
Self-assembling multidomain peptide (MDP) hydrogels have shown great promise as biomaterials for regenerative medicine. In this work, we explored three main areas to understand the inherent activity of these materials further and expand their biomedical applications. First, we developed a non-ionic self-assembling peptide hydrogel, in which assembly is controlled by balancing aggregation of the amphiphilic core and steric interactions within the peptide termini. From a series of neutral peptides containing helical oligo-hydroxyproline termini, we determined that five hydroxyproline residues in the N and C termini of the MDP provide the required solubility, aggregation, and nanofibrous structure to form a compliant injectable hydrogel. This non-ionic peptide hydrogel is biocompatible and easily degraded in vivo and retains cell viability and induces cell quiescence in vitro. Second, we evaluated how the chemical functionality and ionic charge of different MDP hydrogels impacted the overall host immune response. Using a subcutaneous injection model, we characterized the cellular infiltrate of four peptide hydrogels with similar structural and mechanical properties, but with different chemical functionalities and charge. Peptides bearing carboxylate groups evoke minimal inflammation and are quickly remodeled and degraded by tissue-resident macrophages. The lysine-based peptide hydrogel induces acute inflammatory responses that resolve over time. This immune response characterized by blood vessel formation, macrophage infiltration, and collagen deposition may be ideal for tissue regeneration applications. On the other hand, peptide hydrogel containing guanidinium ions causes higher inflammation with a constant presence of granulocytes, which could lead to chronic inflammation and fibrous encapsulation. The characterization of the host responses to these different peptide hydrogels serves as a valuable resource for the rational design of materials for biomedical applications. Lastly, we explored the efficacy of lysine-based peptide hydrogels to promote peripheral nerve regeneration after a crush injury. We developed several peptide candidates containing short peptide mimics from extracellular matrix proteins. We then evaluated the neurite outgrowth promoting activity of all peptide candidates in vitro and their capacity to promote recovery in a sciatic nerve crush injury model. MDP hydrogels were infiltrated by macrophages and degraded over time, and a few candidates accelerated nerve regeneration and functional recovery. This work demonstrates the versatility of the MDP design and biological responses, and the enormous potential of these biomaterials in tissue regeneration and wound healing.
Prediction, Design, and Control of Self-Assembling Collagen Emulating Peptides
(2021-03-24) Walker, Douglas R; Hartgerink, Jeffrey D
Collagen-emulating peptides possess a high potential for applications ranging from in vivo treatment and imaging to materials design. While this potential is highest for peptides intended for heterotrimer formation, it is these peptides that are still the most difficult to control and design predictably. This difficulty is due to a dearth of known assembly-directing interactions, a wealth of competing assemblies, and an absence of reliable prediction algorithms to assess the possible arrangements. Herein we approach this problem through a cyclic method of studying amino acid substitutions and pairwise interactions in collagen-like triple helices, translating this information to stabilizing effects for use in a thermal stability prediction algorithm, using old peptides from the literature to test the algorithm’s performance, designing new peptides with the algorithm, and recycling this information to expand our understanding of sequence effects. Chapter 1 will describe the state of the field, and discuss, in-depth, eight factors which effect the stability of collagen triple helices including triple helix structure, peptide length, peptide termini, prolyl amino acids, amino acid substitutions, amino acid pairwise interactions, alternative registrations, and helical tip effects. The chapter will also examine current prediction algorithms for assessing collagen stability and if and how they assess each of the eight factors. Directions for potential improvements in the field are discussed for each of the areas. Chapter 2 details our initial investigations of amino acid substitutions and pairwise interactions in regards to collagen. We investigate the quantitative effect of known charge-pair interactions in addition to searching for new interactions by evaluating cation-π amino acid pairs and hydrophobic amino acid pairs. This information is then applied in the design of an algorithm which predicts the thermal stability of collagen mimetic peptide triple helices. Next, this algorithm is used to analyze a library of published triple helices to test its accuracy and is then retrained by machine learning to increase its accuracy and precision of prediction. Finally, the algorithm was utilized to aid in the design of a collagen-emulating heterotrimeric triple helix. This triple helix is fully characterized using CD and multiple NMR experiments to confirm that the composition and register of the folded triple helix match the intended triple helical arrangement. Chapter 3 contains an investigation of the first charge-free interaction employed for collagen triple helix design by using an amide-π pair of amino acids. This interaction was examined, along with a few others, by CD analysis of homotrimers and molecular dynamics simulations. Glutamine was determined to be the appropriate length for interacting with a phenylalanine while asparagine is too short. This interaction was applied in the design of a heterotrimer which was also fully characterized by CD and NMR. Subsequently, the data from these complete characterizations of the homotrimers and the designed heterotrimer was used to retrain the algorithm presented in chapter 2. Chapter 4 discusses a genetic algorithm created to computationally design heterotrimeric triple helices. The synthesis and characterization of five triple helices generated by the algorithm over a span of time are discussed. This work is ongoing and NMR results for two of the generated helices are not yet collected. After the conclusion of this work, the results of the five generated triple helices will be used to further train the algorithm presented in chapter 2. Chapter 5 revisits the themes of chapter 1 and describes the advances in each of the eight factors effecting the stability of collagen triple helices achieved within this thesis.
Self-Assembling MultiDomain Peptides as Scaffolds for Tissue Engineering
(2015-03-12) Kang, Marci KMH; Hartgerink, Jeffrey D; Grande-Allen, K. Jane; Wilson, Lon J
Creating a new generation of biomaterials to support tissue engineering efforts is critical to the development of functional tissues. This thesis describes the initial phases of biomaterial development of seven new MultiDomain Pepties (MDPs): from their design and characterization, to the study of how sequential modifications affect dental stem cell response, and finally examines how different cell lines respond to the same MDP sequence. Four of the new sequences, K3(SL)6K3, K3(SL)7K3, K3(SL)8K3, and K4(SL)6K4, were designed to study the effect of lengthening either the amphiphilic region or charged domains of MDPs. Characterization of the peptides by multiple techniques showed anti- parallel !-sheet structure that forms porous nanofiber hydrogels related to the MDP sequence. The remaining three new MDPs, K2(TL)6K2, K2(TL)6K2GRGDS, and K(TL)2SLRG(TL)3KGRGDS, were used as cell culture scaffolds and were compared to their previously published serine-based counterparts to examine the impact of MDP chemistry on the morphology and proliferation of stem cells from human exfoliated deciduous teeth (SHEDs). Fluorescent staining and confocal microscopy indicated that the serine-based hydrogels were more proliferative; the SHEDs did not require the integrin-binding RGDS sequence to attach and proliferate throughout the hydrogel. The threonine-based gels were more selective as the SHEDs were seen to remain rounded throughout the duration of the experiment in K2(TL)6K2. These results highlighted the difference that scaffold chemistry can make on cell response. NIH/3T3 fibroblasts, and EpH4-Ev mammary epithelial cells were encapsulated and cultured in K2(SL)6K2GRGDS hydrogels. All cell lines proliferated significantly by day eleven. Both the NIH/3T3 cells and the EpH4-Ev cells exhibit typical morphology, with the EpH4-Ev cells even forming organotypic structures. Taken together, the results from this study indicate that MDPs can tolerate a number of sequence modifications and are effective scaffolds for a wide range of cell types, even supporting the formation of organotypic structures when the appropriate bioactive cues are present.
Tailored Release of Bioactive Factors from Composite Multidomain Peptide Hydrogels
(2016-03-28) Wickremasinghe, Navindee Charya; Hartgerink, Jeffrey D; Marti, Angel A; Mikos, Antonios G
Multidomain peptides (MDP) self-assemble to form nanofibrous scaffolds well suited to tissue engineering and regeneration strategies. MDPs can present bioactive cues that promote vital biological responses. Orthogonal self-assembly of MDP and growth factor-loaded liposomes generate supramolecular composite hydrogels. This thesis demonstrates the ability to create a unique hydrogel, developed by stepwise self-assembly of multidomain peptide fibers and liposomes, and presents its potential for in vivo applications. Chapter One of the thesis presents an introduction to the above work with background spanning from the role of self-assembling peptides and hydrogels in tissue engineering, to current strategies for therapeutic angiogenesis and wound healing. Chapter Two addresses the design and characterization of a composite hydrogel containing MDP and liposomes. Results showed that structural and mechanical integrity of the peptide nanofibers, lipid vesicles and the composite gel are retained. The two-component gel allows for controlled release of bioactive factors at multiple time points and indicates bimodal release of two growth factors from the same system. These MDP-Liposome Composites (MLCs) were injected in vivo for targeted, localized delivery of growth factors, and Chapter Three details how they functioned in vivo. Placental growth factor-1 (PlGF-1) was shown to temporally stimulate VEGF-receptor activation in vitro in endothelial cells, and robust vessel formation in vivo. MLCs provide a novel method for the time controlled delivery of growth factors from within highly biocompatible and injectable hydrogels. Time controlled release guided by MLCs induces an unprecedented level of growth factor-mediated neovascular maturity. Use of cytokine-loaded MDP hydrogels to accelerate diabetic wound healing is another in vivo application explored in Chapter Four of this thesis. Delivery of a pro-healing cytokine IL-4 via MDP hydrogels have resulted in enhanced healing of full-thickness dermal wounds on the backs of genetically diabetic mice. Compared to controls, wounds treated with IL-4-MDP composite gels showed higher wound closure, M2 macrophage polarization, re-epithelialization, granulation tissue formation and angiogenesis. The conclusion chapter, Chapter Five, discusses how the above in vivo success of composite MDP hydrogels speaks to their potential to function as a unique protein delivery platform for tissue regeneration.

Browsing by Author "Hartgerink, Jeffrey D"

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