Market valuation of environmental performance

This research investigated the general association between corporate environmental performance and the firms’ annual returns independent of any particular environmental event. The association analysis was based on the most recent environmental data for the years 2006, 2007, and 2008. The results indicated that while some environmental variables were significantly associated with firms’ returns, the majority were not. The results also indicated that environmental concerns were more likely to be associated with increase in the firm value than were environmental strengths; however, there were no mean differences between firms whose environmental performance increased as compared with those whose performance deteriorated. Overall, the results provided support for the perspective that environmental strengths require firm expenditures that place additional financial burdens on firms, resulting in lower stock returns.^

An examination of accounting and auditing issues related to strategic environmental initiatives

Although corporate environmental accountability is receiving unprecedented attention in the United States from policy makers, the capital market, and the public at large, extant research is limited in its examination of the implications of strategic corporate environmental initiatives on accounting and auditing. The purpose of my dissertation is to address these implications by examining the association between firm environmental initiatives and audit fees, capital expenditures, and earnings quality using multivariate regression analysis. I find that firms engaged in more strategic environmental initiatives tend to have significantly higher audit fees and capital expenditures, and significantly lower levels of earnings manipulation measured using discretionary accruals. These results support the notion that auditors do recognize the importance of environmental initiatives when conducting the year-end financial statement audit, an idea that positively reflects upon the auditor’s monitoring role. The results also demonstrate the increased amount of capital resources required to participate in strategic environmental initiatives, an anecdotal notion that had yet to be empirically supported. This empirical support provides valuable insights on how environmental initiatives materially impact corporate financial statements. Finally, my results extend the extant literature by demonstrating that the superior financial performance reported by environmentally active firms is less likely driven by earnings manipulation by management, and by implication, more likely a result of real economic gains. Taken together, my dissertation establishes a strong and timely foundation for current and future research to explore corporate environmental initiatives in the United States and globally, a topic increasingly gaining momentum in today’s more eco-conscious world.^

Investigating the outcomes of two chronic disease self-management programs and understanding the correlates of completion for each program

Chronic disease affects 80% of adults over the age of 65 and is expected to increase in prevalence. To address the burden of chronic disease, self-management programs have been developed to increase self-efficacy and improve quality of life by reducing or halting disease symptoms. Two programs that have been developed to address chronic disease are the Chronic Disease Self-Management Program (CDSMP) and Tomando Control de su Salud (TCDS). CDSMP and TCDS both focus on improving participant self-efficacy, but use different curricula, as TCDS is culturally tailored for the Hispanic population. Few studies have evaluated the effectiveness of CDSMP and TCDS when translated to community settings. In addition, little is known about the correlation between demographic, baseline health status, and psychosocial factors and completion of either CDSMP or TCDS. This study used secondary data collected by agencies of the Healthy Aging Regional Collaborative from 10/01/2008–12/31/2010. The aims of this study were to examine six week differences in self-efficacy, time spent performing physical activity, and social/role activity limitations, and to identify correlates of program completion using baseline demographic and psychosocial factors. To examine if differences existed a general linear model was used. Additionally, logistic regression was used to examine correlates of program completion. Study findings show that all measures showed improvement at week six. For CDSMP, self-efficacy to manage disease (p = .001), self-efficacy to manage emotions (p = .026), social/role activities limitations (p = .001), and time spent walking (p = .008) were statistically significant. For TCDS, self-efficacy to manage disease (p = .006), social/role activities limitations (p = .001), and time spent walking (p = .016) and performing other aerobic activity (p = .005) were significant. For CDSMP, no correlates predicting program completion were found to be significant. For TCDS, participants who were male (OR=2.3, 95%CI: 1.15–4.66), from Broward County (OR=2.3, 95%CI: 1.27–4.25), or living alone (OR=2.0, 95%CI: 1.29-–3.08) were more likely to complete the program. CDSMP and TCDS, when implemented through a collaborative effort, can result in improvements for participants. Effective chronic disease management can improve health, quality of life, and reduce health care expenditures among older adults.

Defense Expenditure: Central America and The Dominican Republic

It is often speculated that the high allocation of funds to retirement pension systems has influenced the capacity of Central American and Dominican Republic military to modernize. Yet, the comparative study of the allocation of pension and social funds in these particular countries suggest that there is not direct linkage between the poor funding of military modernization plans and the allocation of funds to military pension systems. The research conducted on this subject shows the following results: 1. The Dominican Republic is the only country that has embarked on a considerable procurement of modern equipment and still reports the largest proportion of social expenditures. 2. El Salvador’s defense budget allocates minimal funding to Social Welfare Institute, which as alternative sources of funding. In 2009, El Salvador increased 15 percent funding to the military to respond to increased role in domestic security issues. 3. The Guatemalan defense expenditure on social programs is fairly low, but it has grown during the past six years due to processes of demobilization. However, the Military Social Welfare Institute is administered by a decentralized institution funded directly by the Ministry of Finance. If it were to be considered as a part of the defense budget, its social expenses would account for almost 16% of it. 4. The Honduran Defense Budget has faced a considerable enlargement during the past four years, with social spending expenses taken precedence over modernization efforts. 2 5. The Nicaraguan system of military pensions is administered by a decentralized entity (IPSM) through a system of salary deductions. Information on the funding of this entity is inconclusive. The Nicaraguan Defense spending on social services has reported a drastic 90% drop since the year 2007.

Essays in economic growth, political economy and institutions

This dissertation analyzes the effects of political and economic institutions on economic development and growth.^ The first essay develops an overlapping-generations political economy model to analyze the incentives of various social groups to finance human capital accumulation through public education expenditures. The contribution of this study to the literature is that it helps explain the observed differences in the economic growth performance of natural resource-abundant countries. The results suggest that the preferred tax rates of the manufacturers on one hand and the political coalition of manufacturers and landowners, on the other hand, are equal to the socially optimal tax rate. However, we show that owners of natural resources prefer an excessively high tax rate, which suppresses aggregate output to a suboptimal level.^ The second essay examines the relationship between the political influence of different social classes and public education spending in panel data estimation. The novel contribution of this paper to the literature is that I proxy the political power and influence of the natural resource owners, manufacturers, and landowners with macroeconomic indicators. The motivation behind this modeling choice is to substantiate the definition of the political power of social classes with economic fundamentals. I use different governance indicators in the estimations to find out how different institutions mediate the overall impact of the political influence of various social classes on public education spending. The results suggest that political stability and absence of violence and rule of law are the important governance indicators.^ The third essay develops a counter argument to Acemoglu et al. (2010) where the thesis is that French institutions and economic reforms fostered economic progress in those German regions invaded by the Napoleonic armies. By providing historical data on urbanization rates used as proxies for economic growth, I demonstrate that similar different rates of economic growth were observed in the regions of France in the post-Napoleonic period as well. The existence of different economic growth rates makes it hard to argue that the differences in economic performance in the German regions that were invaded by the French and those that were spared a similar fate follow from regional differences in economic institutions.^

Conceptualizing American power and security in a post -9/11 security context: Conflict, resistance, and global security, 2001–present

In a post-Cold War, post-9/11 world, the advent of US global supremacy resulted in the installation, perpetuation, and dissemination of an Absolutist Security Agenda (hereinafter, ASA). The US ASA explicitly and aggressively articulates and equates US national security interests with the security of all states in the international system, and replaced the bipolar, Cold War framework that defined international affairs from 1945-1992. Since the collapse of the USSR and the 11 September 2001 terrorist attacks, the US has unilaterally defined, implemented, and managed systemic security policy. The US ASA is indicative of a systemic category of knowledge (security) anchored in variegated conceptual and material components, such as morality, philosophy, and political rubrics. The US ASA is based on a logic that involves the following security components: (1) hyper militarization, (2) intimidation,(3) coercion, (4) criminalization, (5) panoptic surveillance, (6) plenary security measures, and (7) unabashed US interference in the domestic affairs of select states. Such interference has produced destabilizing tensions and conflicts that have, in turn, produced resistance, revolutions, proliferation, cults of personality, and militarization. This is the case because the US ASA rests on the notion that the international system of states is an extension, instrument of US power, rather than a system and/or society of states comprised of functionally sovereign entities. To analyze the US ASA, this study utilizes: (1) official government statements, legal doctrines, treaties, and policies pertaining to US foreign policy; (2) militarization rationales, budgets, and expenditures; and (3) case studies of rogue states. The data used in this study are drawn from information that is publicly available (academic journals, think-tank publications, government publications, and information provided by international organizations). The data supports the contention that global security is effectuated via a discrete set of hegemonic/imperialistic US values and interests, finding empirical expression in legal acts (USA Patriot ACT 2001) and the concept of rogue states. Rogue states, therefore, provide test cases to clarify the breadth, depth, and consequentialness of the US ASA in world affairs vis-à-vis the relationship between US security and global security.

Altered Landscape or Arms Race? Making Sense of Military Spending in South America

In 2009, South American military spending reached a total of $51.8 billion, a fifty percent increased from 2000 expenditures. The five-year moving average of arms transfers to South America was 150 percent higher from 2005 to 2009 than figures for 2000 to 2004.[1] These figures and others have led some observers to conclude that Latin America is engaged in an arms race. Other reasons, however, account for Latin America’s large military expenditure. Among them: Several countries have undertaken long-prolonged modernization efforts, recently made possible by six years of consistent regional growth.[2] A generational shift is at hand. Armed Forces are beginning to shed the stigma and association with past dictatorial regimes.[3] Countries are pursuing specific individual strategies, rather than reacting to purchases made by neighbors. For example, Brazil wants to attain greater control of its Amazon rainforests and offshore territories, Colombia’s spending demonstrates a response to internal threats, and Chile is continuing a modernization process begun in the 1990s.[4] Concerns remain, however: Venezuela continues to demonstrate poor democratic governance and a lack of transparency; neighbor-state relations between Colombia and Venezuela, Peru and Chile, and Bolivia and Paraguay, must all continue to be monitored; and Brazil’s military purchases, although legitimate, will likely result in a large accumulation of equipment.[5] These concerns can be best addressed by strengthening and garnering greater participation in transparent procurement mechanism.[6] The United States can do its part by supporting Latin American efforts to embrace the transparency process. _________________ [1] Bromley, Mark, “An Arms Race in Our Hemisphere? Discussing the Trends and Implications of Military Expenditures in South America,” Brookings Institution Conference, Washington, D.C., June 3rd, 2010, Transcript Pgs. 12,13, and 16 [2] Robledo, Marcos, “The Rearmament Debate: A Chilean Perspective,” Power Point presentation, slide 18, 2010 Western Hemisphere Security Colloquium, Miami, Florida, May 25th-26th, 2010 [3] Yopo, Boris, “¿Carrera Armamentista en la Regiόn?” La Tercera, November 2nd, 2009, http://www.latercera.com/contenido/895_197084_9.shtml, accessed October 8th, 2010 [4] Walser, Ray, “An Arms Race in Our Hemisphere? Discussing the Trends and Implications of Military Expenditures in South America,” Brookings Institution Conference, Washington, D.C., June 3rd, 2010, Transcript Pgs. 49,50,53 and 54 [5] Ibid., Guevara, Iñigo, Pg. 22 [6] Ibid., Bromley, Mark, Pgs. 18 and 19

The relationship between higher education curricular variables and human flight performance in a preliminary flying training program

The ability of the United States Air Force (USAF) to sustain a high level of operational ability and readiness is dependent on the proficiency and expertise of its pilots. Recruitment, education, training, and retention of its pilot force are crucial factors in the USAF's attainment of its operational mission: defense of this nation and its allies. Failure of a student pilot during a training program does not only represent a loss of costly training expenditures to the American public, but often consists of loss of human life, aircraft, and property. This research focused on the Air Force Reserve Officer Training Corps' (AFROTC) selection method for student pilots for the light aircraft training (LATR) program. The LATR program is an intense 16 day flight training program that precedes the Air Force's undergraduate pilot training (UPT) program. The study subjects were 265 AFROTC cadets in the LATR program. A variety of independent variables from each subject's higher education curricular background as well as results of preselection tests, participation in varsity athletics, prior flying experience and gender were evaluated against subsequent performance in LATR. Performance was measured by a quantitative performance score developed by this researcher based on 28 graded training factors as well as overall pass or fail of the LATR program. Study results showed participation in university varsity athletics was very significantly and positively related to performance in the LATR program, followed by prior flying experience and to a very slight degree portions of the Air Force Officers Qualifying Test. Not significantly related to success in the LATR program were independent variables such as grade point average, scholastic aptitude test scores, academic major, gender and the AFROTC selection and ranking system.

A study of the top executive conference centers in the United States and an examination of the corresponding corporate meetings market

Introduction: The United States today has become "meeting-conscious." The complexity of conducting business has led to the need for sophisticated coordination of decision-making processes on all levels of the organization. Company meetings have played an increasingly important role in the success and future of many companies. Strategies and decisions are developed at meetings that can determine future policies of crucial importance. Executive training can mean the difference in whether the company will even survive. Large and growing companies have increased their off-premise meeting budgets annually in spite of the state of the economy. however, the rising costs of travel and lodging have made management monitor these budgets more closely than ever. Thus, the need to use every dollar efficiently has compelled companies to examine newer methods of running meetings and alternatives to the usage of typical off-premise meeting facilities. The importance of off-premise meetings in the United States economy has greatly increased due to the billions of dollars spent annually. These factors make it vital to explore the effectiveness of time and monetary expenditures. Up until the mid-1960's, company meetings were held in facilities of various design and purpose, none of which were specifically designed for the small to medium corporate meeting. Upon gathering information concerning the meetings market and the corporate meeting planner, certain individuals endeavored to change the situation. This study is designed to investigate this new concept, which will hereafter be referred to as "conference center." For the purpose of this study, the following two definitions will be used. 1. Conference center - that meeting facility primarily marketing its facilities for the small to medium-sized corporate meeting. The center is operated by specialists aware of market needs in as much detail as are those people working for the company involved. On-premise sleeping rooms are not mandatory provided such facilities are within easy access. 2. Meeting planner - that person within an organization who has primary responsibility for arranging off-premise meetings and all other related items necessary for meeting effectiveness. This person may spend anywhere from 10 to 100l of his time in this capacity. The conference center has effectively satisfied the need for specialized corporate meeting facilities. This study will show the depth of the corporate meetings market and trace the growth and development of this relatively new conference center concept. Information will also be compiled on the top centers in the country. It is hoped that by presenting this research meeting planners will become more aware of the nature and location of these centers, especially for use by the small to medium-sized company. Such exposure of the centers will hopefully increase existing demand and enable the construction of new, innovative centers.

Conceptualizing American power and security in a post-9/11 security context : conflict, resistance, and global security, 2001-present

In a post-Cold War, post-9/11 world, the advent of US global supremacy resulted in the installation, perpetuation, and dissemination of an Absolutist Security Agenda (hereinafter, ASA). The US ASA explicitly and aggressively articulates and equates US national security interests with the security of all states in the international system, and replaced the bipolar, Cold War framework that defined international affairs from 1945-1992. Since the collapse of the USSR and the 11 September 2001 terrorist attacks, the US has unilaterally defined, implemented, and managed systemic security policy. The US ASA is indicative of a systemic category of knowledge (security) anchored in variegated conceptual and material components, such as morality, philosophy, and political rubrics. The US ASA is based on a logic that involves the following security components: 1., hyper militarization, 2., intimidation, 3., coercion, 4., criminalization, 5., panoptic surveillance, 6., plenary security measures, and 7., unabashed US interference in the domestic affairs of select states. Such interference has produced destabilizing tensions and conflicts that have, in turn, produced resistance, revolutions, proliferation, cults of personality, and militarization. This is the case because the US ASA rests on the notion that the international system of states is an extension, instrument of US power, rather than a system and/or society of states comprised of functionally sovereign entities. To analyze the US ASA, this study utilizes: 1., official government statements, legal doctrines, treaties, and policies pertaining to US foreign policy; 2., militarization rationales, budgets, and expenditures; and 3., case studies of rogue states. The data used in this study are drawn from information that is publicly available (academic journals, think-tank publications, government publications, and information provided by international organizations). The data supports the contention that global security is effectuated via a discrete set of hegemonic/imperialistic US values and interests, finding empirical expression in legal acts (USA Patriot ACT 2001) and the concept of rogue states. Rogue states, therefore, provide test cases to clarify the breadth, depth, and consequentialness of the US ASA in world affairs vis-a-vis the relationship between US security and global security.

A tributação como instrumento de proteção ambiental no Brasil

The Federal Constitution of 1988 gave special treatment to the issue of the environment, raising this diffuse right to the status of a fundamental right. In order to preserve it, the constitutional order is provided with various means to this purpose, including the possibility of using taxation. Several principles both constitutional, as infraconstitucional, support the use of taxation as a legal instrument to protect the environment. There is an intense legal debate about the suitability, characteristics, purposes and principles which underlie and restrict the environmental taxation. Discussions and proposals for reform of the tax system in order to include the ecological aspect at its core have been developed. The use of taxation as a way to fund public expenditures related to environmental causes, promote the internalization of negative externalities and as a way to induce behavior to benefit the environment finds support in the Brazilian legal system. This paper seeks to demonstrate that the national tax system is fully able to act as a tool available to the state for the implementation of the fundamental right to an ecologically balanced environment, whether through the taxes fiscal role or due, mainly, through the phenomenon of extrafiscality. Also, it is intended, through doctrinal, jurisprudential analysis and concrete cases, to investigate whether the tax system can be effective in protecting the environment in the way it is currently constructed, or if there is need to proceed with changes in its structure in order to achieve this goal

Os rumos do fundo público no capitalismo contemporâneo: uma análise sobre o financiamento da Política de saúde no estado do Rio Grande do Norte

This work analizes the financing of Health Policies on the state of Rio Grande Do Norte, starting at the presumption that SUS is “Bombarded” by fiscal ajustments, as a neoliberal strategy to face capital crises.The trafectory of the financing of SUS demands the comprehension of two principles which are, in essence, contradictory: the “principle of universatility”, which is caracterized by the uncompromising defence of the fundaments of the Sanitary Reform, and the “principle of containment of social costs”, articulating the macroeconomic policy that has being developed in Brazil since the 1990s and which substantiantes itself on the 2000s.This last defends the reduction of the social costs, the maintanance of primary surplus and the privatization of public social services. Considering these determinations, the objective of this research constitues in bringing a critical reflection sorrounding the financing of the Health Policies on the state of Rio Grande do Norte, on the period from 2004 to 2012.Starting from a bibliografic and documentary research, it sought out to analyze the budget planning forseen on the Budget Guideline Law (LDO) and on the Multiannual Plans (PPA), investigating the reports of the Court of Auditors of the State of RN and gathering information about expenses with health, available on the System of Information About Public Budgeting in Health (SIOPS).The Analises of the data obtained, in light of the theoretic referece chosen, reveals trends in the public budget setting for health on the State of Rio Grande do Norte, which are: a tiny share of investment expenditure on health, when compared to other expenses, the amount used in daily fees and advertising; the high expense in personnel expenses, especially for hiring medical cooperatives;the strong dependence of the state on revenue transferences from the Union; the aplication of resources in actions of other nature considered as health, in exemple of the expenditures undertaken by the budgeting unit Supplying Center S/A (CEASA) on the function of health and subfunction of prophylactic and therapeutic and on the Popular Pharmacy program. Since 2006, expenses refering to Regime Security Servers (RPPA) on the area of health also have being considered as public actions and services in health for constitutional limit ends, beyond the inconsistencies on the PPAs with the actions performed efectively.

Malaria prevention in north-eastern Tanzania: patterns of expenditure and determinants of demand at the household level.

Objective. This study aims to provide a better understanding of the amounts spent on different malaria prevention products and the determinants of these expenditures. Methods. 1,601 households were interviewed about their expenditure on malaria mosquito nets in the past five years, net re-treatments in the past six months and other expenditures prevention in the past two weeks. Simple random sampling was used to select villages and streets while convenience sampling was used to select households. Expenditure was compared across bed nets, aerosols, coils, indoor spraying, using smoke, drinking herbs and cleaning outside environment. Findings. 68% of households owned at least one bed net and 27% had treated their nets in the past six months. 29% were unable to afford a net. Every fortnight, households spent an average of US $0.18 on nets and their treatment, constituting about 47% of total prevention expenditure. Sprays, repellents and coils made up 50% of total fortnightly expenditure (US$0.21). Factors positively related to expenditure were household wealth, years of education of household head, household head being married and rainy season. Poor quality roads and living in a rural area had a negative impact on expenditure. Conclusion. Expenditure on bed nets and on alternative malaria prevention products was comparable. Poor households living in rural areas spend significantly less on all forms of malaria prevention compared to their richer counterparts. Breaking the cycle between malaria and poverty is one of the biggest challenges facing malaria control programmes in Africa.

Beyond the Convent Walls: The Local and Japan-wide Activities of Daihongan’s Nuns in the Early Modern Period (c. 1550–1868)

This dissertation examines the social and financial activities of Buddhist nuns to demonstrate how and why they deployed Buddhist doctrines, rituals, legends, and material culture to interact with society outside the convent. By examining the activities of the nuns of the Daihongan convent (one of the two administrative heads of the popular pilgrimage temple, Zenkōji) in Japan’s early modern period (roughly 1550 to 1868) as documented in the convent’s rich archival sources, I shed further light on the oft-overlooked political and financial activities of nuns, illustrate how Buddhist institutions interacted with the laity, provide further nuance to the discussion of how Buddhist women navigated patriarchal sectarian and secular hierarchies, and, within the field of Japanese history, give voice to women who were active outside of the household unit around which early modern Japanese society was organized.

Zenkōji temple, surrounded by the mountains of Nagano, has been one of Japan’s most popular pilgrimage sites since the medieval period. The abbesses of Daihongan, one Zenkōji’s main sub-temples, traveled widely to maintain connections with elite and common laypeople, participated in frequent country-wide displays of Zenkōji’s icon, and oversaw the creation of branch temples in Edo (now Tokyo), Osaka, Echigo (now Niigata), and Shinano (now Nagano). The abbesses of Daihongan were one of only a few women to hold the imperially sanctioned title of eminent person (shōnin 上人) and to wear purple robes. While this means that this Pure Land convent was in some ways not representative of all convents in early modern Japan, Daihongan’s position is particularly instructive because the existence of nuns and monks in a single temple complex allows us to see in detail how monastics of both genders interacted in close quarters.

This work draws heavily from the convent’s archival materials, which I used as a guide in framing my dissertation chapters. In the Introduction I discuss previous works on women in Buddhism. In Chapter 1, I briefly discuss the convent’s history and its place within the Zenkōji temple complex. In Chapter 2, I examine the convent’s regular economic bases and its expenditures. In Chapter 3, I highlight Daihongan’s branch temples and discuss the ways that they acted as nodes in a network connecting people in various areas to Daihongan and Zenkōji, thus demonstrating how a rural religious center extended its sphere of influence in urban settings. In Chapter 4, I discuss the nuns’ travels throughout the country to generate new and maintain old connections with the imperial court in Kyoto, confraternities in Osaka, influential women in the shogun’s castle, and commoners in Edo. In Chapter 5, I examine the convent’s reliance upon irregular means of income such as patronage, temple lotteries, loans, and displays of treasures, and how these were needed to balance irregular expenditures such as travel and the maintenance or reconstruction of temple buildings. Throughout the dissertation I describe Daihongan’s inner social structure comprised of abbesses, nuns, and administrators, and its local emplacement within Zenkōji and Zenkōji’s temple lands.

Exploring these themes sheds light on the lives of Japanese Buddhist nuns in this period. While the tensions between freedom and agency on the one hand and obligations to patrons, subordination to monks, or gender- and status-based restrictions on the other are important, and I discuss them in my work, my primary focus is on the nuns’ activities and lives. Doing so demonstrates that nuns were central figures in ever-changing economic and social networks as they made and maintained connections with the outside world through Buddhist practices and through precedents set centuries before. This research contributes to our understanding of nuns in Japan’s early modern period and will participate in and shape debates on the roles of women in patriarchal religious hierarchies.

Bioengineered Approaches to Prevent Hypertrophic Scar Contraction

Burn injuries in the United States account for over one million hospital admissions per year, with treatment estimated at four billion dollars. Of severe burn patients, 30-90% will develop hypertrophic scars (HSc). Current burn therapies rely upon the use of bioengineered skin equivalents (BSEs), which assist in wound healing but do not prevent HSc. HSc contraction occurs of 6-18 months and results in the formation of a fixed, inelastic skin deformity, with 60% of cases occurring across a joint. HSc contraction is characterized by abnormally high presence of contractile myofibroblasts which normally apoptose at the completion of the proliferative phase of wound healing. Additionally, clinical observation suggests that the likelihood of HSc is increased in injuries with a prolonged immune response. Given the pathogenesis of HSc, we hypothesize that BSEs should be designed with two key anti-scarring characterizes: (1) 3D architecture and surface chemistry to mitigate the inflammatory microenvironment and decrease myofibroblast transition; and (2) using materials which persist in the wound bed throughout the remodeling phase of repair. We employed electrospinning and 3D printing to generate scaffolds with well-controlled degradation rate, surface coatings, and 3D architecture to explore our hypothesis through four aims.

In the first aim, we evaluate the impact of elastomeric, randomly-oriented biostable polyurethane (PU) scaffold on HSc-related outcomes. In unwounded skin, native collagen is arranged randomly, elastin fibers are abundant, and myofibroblasts are absent. Conversely, in scar contractures, collagen is arranged in linear arrays and elastin fibers are few, while myofibroblast density is high. Randomly oriented collagen fibers native to the uninjured dermis encourage random cell alignment through contact guidance and do not transmit as much force as aligned collagen fibers. However, the linear ECM serves as a system for mechanotransduction between cells in a feed-forward mechanism, which perpetuates ECM remodeling and myofibroblast contraction. The electrospinning process allowed us to create scaffolds with randomly-oriented fibers that promote random collagen deposition and decrease myofibroblast formation. Compared to an in vitro HSc contraction model, fibroblast-seeded PU scaffolds significantly decreased matrix and myofibroblast formation. In a murine HSc model, collagen coated PU (ccPU) scaffolds significantly reduced HSc contraction as compared to untreated control wounds and wounds treated with the clinical standard of care. The data from this study suggest that electrospun ccPU scaffolds meet the requirements to mitigate HSc contraction including: reduction of in vitro HSc related outcomes, diminished scar stiffness, and reduced scar contraction. While clinical dogma suggests treating severe burn patients with rapidly biodegrading skin equivalents, these data suggest that a more long-term scaffold may possess merit in reducing HSc.

In the second aim, we further investigate the impact of scaffold longevity on HSc contraction by studying a degradable, elastomeric, randomly oriented, electrospun micro-fibrous scaffold fabricated from the copolymer poly(l-lactide-co-ε-caprolactone) (PLCL). PLCL scaffolds displayed appropriate elastomeric and tensile characteristics for implantation beneath a human skin graft. In vitro analysis using normal human dermal fibroblasts (NHDF) demonstrated that PLCL scaffolds decreased myofibroblast formation as compared to an in vitro HSc contraction model. Using our murine HSc contraction model, we found that HSc contraction was significantly greater in animals treated with standard of care, Integra, as compared to those treated with collagen coated-PLCL (ccPLCL) scaffolds at d 56 following implantation. Finally, wounds treated with ccPLCL were significantly less stiff than control wounds at d 56 in vivo. Together, these data further solidify our hypothesis that scaffolds which persist throughout the remodeling phase of repair represent a clinically translatable method to prevent HSc contraction.

In the third aim, we attempt to optimize cell-scaffold interactions by employing an anti-inflammatory coating on electrospun PLCL scaffolds. The anti-inflammatory sub-epidermal glycosaminoglycan, hyaluronic acid (HA) was used as a coating material for PLCL scaffolds to encourage a regenerative healing phenotype. To minimize local inflammation, an anti-TNFα monoclonal antibody (mAB) was conjugated to the HA backbone prior to PLCL coating. ELISA analysis confirmed mAB activity following conjugation to HA (HA+mAB), and following adsorption of HA+mAB to the PLCL backbone [(HA+mAB)PLCL]. Alican blue staining demonstrated thorough HA coating of PLCL scaffolds using pressure-driven adsorption. In vitro studies demonstrated that treatment with (HA+mAB)PLCL prevented downstream inflammatory events in mouse macrophages treated with soluble TNFα. In vivo studies using our murine HSc contraction model suggested positive impact of HA coating, which was partiall impeded by the inclusion of the TNFα mAB. Further characterization of the inflammatory microenvironment of our murine model is required prior to conclusions regarding the potential for anti-TNFα therapeutics for HSc. Together, our data demonstrate the development of a complex anti-inflammatory coating for PLCL scaffolds, and the potential impact of altering the ECM coating material on HSc contraction.

In the fourth aim, we investigate how scaffold design, specifically pore dimensions, can influence myofibroblast interactions and subsequent formation of OB-cadherin positive adherens junctions in vitro. We collaborated with Wake Forest University to produce 3D printed (3DP) scaffolds with well-controlled pore sizes we hypothesized that decreasing pore size would mitigate intra-cellular communication via OB-cadherin-positive adherens junctions. PU was 3D printed via pressure extrusion in basket-weave design with feature diameter of ~70 µm and pore sizes of 50, 100, or 150 µm. Tensile elastic moduli of 3DP scaffolds were similar to Integra; however, flexural moduli of 3DP were significantly greater than Integra. 3DP scaffolds demonstrated ~50% porosity. 24 h and 5 d western blot data demonstrated significant increases in OB-cadherin expression in 100 µm pores relative to 50 µm pores, suggesting that pore size may play a role in regulating cell-cell communication. To analyze the impact of pore size in these scaffolds on scarring in vivo, scaffolds were implanted beneath skin graft in a murine HSc model. While flexural stiffness resulted in graft necrosis by d 14, cellular and blood vessel integration into scaffolds was evident, suggesting potential for this design if employed in a less stiff material. In this study, we demonstrate for the first time that pore size alone impacts OB-cadherin protein expression in vitro, suggesting that pore size may play a role on adherens junction formation affiliated with the fibroblast-to-myofibroblast transition. Overall, this work introduces a new bioengineered scaffold design to both study the mechanism behind HSc and prevent the clinical burden of this contractile disease.

Together, these studies inform the field of critical design parameters in scaffold design for the prevention of HSc contraction. We propose that scaffold 3D architectural design, surface chemistry, and longevity can be employed as key design parameters during the development of next generation, low-cost scaffolds to mitigate post-burn hypertrophic scar contraction. The lessening of post-burn scarring and scar contraction would improve clinical practice by reducing medical expenditures, increasing patient survival, and dramatically improving quality of life for millions of patients worldwide.