Edinburgh Research Explorer From laboratory to clinic

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Introduction
C ommercializing scientific discoveries are a com- plex process.Taking these discoveries from the laboratory to the clinic, especially for life science inventions, involves commitment from and interactions by individual agents with a myriad of organizational support entities and institutions.Scientific discoveries often emanate from universities (i.e., institutions); technology transfer offices (TTOs) (i.e., organizational support entities) working alongside academics (i.e., individual agents) facilitate the translation of these discoveries across the universityindustry boundary to the marketplace (Rothaermel et al., 2007).This interplay of individual agents, organizational support entities, and institutions form the basis of a university-centered entrepreneurial ecosystem (UCEE).
Research on UCEEs as a distinctive entity remains scarce, especially their role as a facilitator of or obstructer to possible commercialization pathways.Since science commercialization is characterized by multifaceted agent-organization-institution interactions, studying science commercialization from a UCEE perspective is critical.UCEEs have been described as a fulcrum for commercial activity, characterized by the dynamic relationship between agents, organizations, and institutions, which facilitates technology transfer activities (Johnson et al., 2019).This multitude of agents, organizational support entities, and institutions within UCEEs suggests the need for richer theory (Chang et al., 2016;Fini et al., 2017), which can model their divergent interactions, particularly when commercialization uncertainties exist (Neves and Franco, 2016;Johnson and Bock, 2017).
To account for these agent-organizationinstitution interactions, research has expanded beyond single-level studies to investigate multi-level studies.Recent research has investigated the complex relationship between individual and university institutional factors on entrepreneurial behavior and commercial activity (Huyghe and Knockaert, 2015;Wu et al., 2015;Eesley et al., 2016).Yet, this research has limits since it generally considers individual and university institutional factors in isolation, failing to recognize the bi-directional relationship of academic entrepreneurship.We address the limitations of both single-and multi-level research by investigating the bi-directional relationship between individual agents and their institutional environments to understand how this influences science commercialization within UCEEs.This bi-directional relationship is important, and our multi-level study affords us the opportunity to unpack both sides of UCEE engagement, specifically, how institutions act on agents and how agents act on institutions.While empirical research has confirmed how entrepreneurial institutions act on agents to promote or hinder science commercialization activities (Rothaermel et al., 2007), less is known about the other side of this dynamic relationshiphow UCEE agents act on institutions.Accordingly, we ask: how do UCEE agents respond and adapt to institutional commercialization mandates during science commercialization?
Scholars have emphasized the importance of science commercialization as a rich context to develop and test theory (Fini et al., 2019), including the critical role of individual agents in science commercialization (Hmieleski and Powell, 2018).Therefore, we focus our study on a cross-national investigation of regenerative medicine commercialization.To address our research question, we employ an inductive, qualitative methodology consisting of 47 narrative interviews with a variety of agents -that is, scientists, entrepreneurs, executive-level individuals from organizational support entities -embedded in a UCEE and involved in the commercialization of regenerative medicine across three universities, one each in the United States (US), United Kingdom (UK), and Russia.
Our study makes two important contributions to the academic entrepreneurship and science commercialization literature.First, it highlights the dynamic interactions between UCEE agents and institutions during science commercialization within UCEEs.This bi-directional relationship between individual agents and institutions, as well as a focus on UCEEs, facilitates a much-needed multi-level perspective on academic entrepreneurship research (Klingbeil et al., 2019).We reveal how UCEE agents respond and adapt to institutional science commercialization mandates.Specifically, we show how UCEE agents act on institutions through a variety of behavioral responses to prevailing rules and norms ranging from adhering (i.e., strictly following), sidestepping (i.e., partly following), to violating them (i.e., strictly ignoring).This enables UCEE agents to pursue an established or create a new path toward science commercialization.This provides us with the opportunity to delineate how aligned agent-institution engagements within UCEEs reflects an ecosystem that is engineered while misaligned agent-institution engagements underscore an ecosystem that coevolves (Ritala and Almpanopoulou, 2017).
Second, our focus on UCEE agents affords us the opportunity to address the limited efforts to unpack the microfoundations of science commercialization (Fini et al., 2018;Hmieleski and Powell, 2018) and entrepreneurial ecosystems (Wurth et al., 2021), as well as bring multiple agent voices from within the UCEE to the forefront of ecosystem research (Hakala et al., 2020).We reveal how behavioral responses by UCEE agents to institutional influences (e.g., constraints) related to commercialization support mechanisms affect science venturing.This is important since these behavioral responses influence the science commercial pathway chosen and entrepreneurial pursuits within UCEEs.Further, these behavioral responses provide feedback to UCEE institutions, which act as signals to adapt its structures, processes, and governance mechanisms.This finding builds upon prior research connecting entrepreneurial processes with entrepreneurial ecosystems (O'Shea et al., 2021).In particular, O'Shea et al. ( 2021) suggests that entrepreneurial ecosystem formation is centered on a process of opportunity co-evolution.We extend their framework by moving beyond the earlier opportunity evolution stage of the entrepreneurial process and, instead, explore the latter stages of the entrepreneurial process -how (science-based) opportunities are commercialized within UCEEs.
In the next section, we review the literature on science commercialization within UCEEs.Next, we detail the methods and data utilized to address our research question.Following this, we present our study findings.We further elaborate upon these observations in our discussion and advance our contributions to theory.Finally, we consider the implications of our findings and provide areas for future research.

Entrepreneurial ecosystems: toward a UCEE
Commercializing science is an inherently risky process; it involves multiple parties with divergent goals that operate across organizational boundaries.Only a few exemplar studies fully describe and explain how entrepreneurial agents act during this process, especially within diverse UCEE settings (cf.Johnson et al., 2019).Investigating the distinctive characteristics of science commercialization associated with entrepreneurial behavior within a UCEE is timely because it helps to explain the complex dynamics of various agents and institutions.The evolution and performance of an entrepreneurial ecosystem is dependent upon the interactions between three critical components -individual agents, organizations (including their organizational agents), and institutions (Brown and Mason, 2017;Spigel, 2017).The behavior and actions of individual agents are central to explaining how entrepreneurial ecosystems function (Stam, 2015;Wurth et al., 2021).Investigating how individual agents dynamically interact with institutions is important to our understanding of entrepreneurial ecosystem evolution.Unfortunately, the interactions between agents, organizations, and institutions remains fuzzy (Alvedalen and Boschma, 2017).
The evolutionary pathway of an entrepreneurial ecosystem depends heavily on individual ecosystem agents but emerges from a highly institutionalized framework.Despite their importance, the dynamics and evolution of entrepreneurial ecosystems are poorly understood (Cho et al., 2021;Dedehayir et al., 2018).Of particular interest, is a greater understanding of 'which parts of the ecosystem are (and can be) engineered and which parts are self-organized or co-evolve' (Ritala and Almpanopoulou, 2017, p. 41).Understanding the role of ecosystems agents in shaping ecosystem evolution is, therefore, timely.While research exploring entrepreneurial ecosystems has been the subject of recent conversations (c.f.Alvedalen and Boschma, 2017;Spigel, 2017;Cho et al., 2021;Wurth et al., 2021), with a few exceptions (c.f.Miller and Acs, 2017;Hayter et al., 2018;Johnson et al., 2019), studies investigating UCEEs are limited.Given the importance of UCEEs to science commercialization activities (Johnson et al., 2019), this limited understanding of UCEEs is problematic.
Science commercialization is, generally, characterized by specialized knowledge requirements, high discovery costs, technological uncertainties, and long gestation periods.Accordingly, science commercialization favors centralization, especially around research universities.UCEEs are embedded networks of agents, supporting organizations, and institutions that reinforce specific technologies.A UCEE forms when these embedded networks of agents, supporting organizations, and institutions respond to (and possibly adapt) institutional commercialization mandates and engage in technology transfer, driving science commercialization and a cluster of new ventures (Johnson et al. 2019).
In knowledge-intensive sectors, such as regenerative medicine, technology transfer activities are challenging (Bock and Johnson, 2018).To make scientific and commercial progress, UCEE agents must navigate institutional mandates.While institutional mandates have been shown to influence UCEE agents to drive science commercialization (Rothaermel et al., 2007), it is unclear how UCEEs remain vibrant and evolve when individual efforts appear frustrated or are deadlocked.We have limited knowledge of how UCEE agents act on institutional mandates when they challenge, or are perceived to challenge, science commercialization.Research has detailed how agents operating in suboptimal institutional environments can still act entrepreneurially to drive commercial activity (Lucas and Fuller, 2017), including strategies to bypass institutional mandates (Gianiodis et al., 2016) and directly engage agents with the UCEE/region (Pugh et al., 2018).Similarly, in some instances of R&D activity, like-minded agents may escape the constraints of institutional mandates, or break with institutional norms, to act entrepreneurially via bootlegging efforts (Criscuolo et al., 2014).Therefore, to understand how UCEE agents respond and adapt to institutional commercialization mandates during science commercialization, a multi-level approach is required.

Multi-level relationships within UCEEs
Entrepreneurial ecosystems evolve based on the dynamic characteristics and interactions between and among agents and institutions (Pitelis, 2012).In this study, we apply a systems view to the behavior of UCEE agents and their interactions with UCEE institutions.Building upon Hakala et al. (2020), we bring in multiple voices and more main characters from within multiple ecosystems.Specifically, we take a much-needed microfoundations approach to entrepreneurial ecosystems (Wurth et al., 2021) to understand how UCEE agents interact with institutions during science commercialization activities.
From an individual-level perspective, behaviors and attitudes of the academic scientist are important in predicting commercialization outcomes (Azagra-Caro and Llopis, 2017;Holley and Watson, 2017).There is an extensive literature that investigates how individual agents influence science commercialization, especially within a university setting (cf.Perkmann et al., 2013;Hmieleski and Powell, 2018;Civera et al., 2020).How individual scientists perceive institutional support may influence their entrepreneurial intention to engage in science commercialization.
At the organizational level, science commercialization is dependent on support functions and intermediaries (Villani et al., 2017;Clayton et al., 2018;Iacobucci et al., 2020).While the literature relies heavily on the study of formal mechanisms, more recent research suggests that commercialization can occur via informal 'back-door' mechanisms, when individuals bypass established TTO commercialization pathways (Markman, 2015;Gianiodis et al., 2016), or via bootlegging activities (Criscuolo et al., 2014).
From an institutional-level perspective, we adopt the approach of Huyghe and Knockaert (2015) and view the organization as institution.In doing so, we recognize that institutional elements surface from within the organization itself and operate across multiple levels (Zucker, 1987;Scott, 2008).At each of these levels -e.g., the UCEE (Johnson et al., 2019), the university (Huyghe and Knockaert, 2015), individual university departments (Rasmussen et al., 2014), or the TTO (Baglieri et al., 2018) -there is either support or barriers to science commercialization activity.
Within UCEEs, universities implement institutional policies, processes, norms, and mandates that seek to support science commercialization in theory but may not always in practice.Despite institutional science commercialization barriers (Bock and Johnson, 2016), research has also found that, even in institutional challenging contexts, scientists still find ways to pursue entrepreneurial activities (Meoli and Vismara, 2016).This suggests that while institutions affect entrepreneurial behavior, individual entrepreneurial activity both influences the institutional environment and/or overcomes its limitations (Lucas and Fuller, 2017).Yet, our understanding of this bi-directional relationship within a UCEE remains limited, especially within the context of academic entrepreneurship.Given this gap in knowledge, our departure is centered on the dynamic between institutions influencing entrepreneurial behavior and institutions being influenced by individual agents.

Methodology
To explore agent-institution dynamics, we investigated science commercialization in the field of stem cell-based regenerative medicine.Since regenerative medicine research is predominantly situated within research institutions, and involves interactions between multiple agents, organizational stakeholders, and institutions, this provided the necessary conditions to explore agent-institution dynamics within a UCEE.At the same time, given the scientific and translational complexities inherent to science commercialization in this field (see Bock and Johnson, 2018), regenerative medicine commercialization represents an excellent context for building and testing theory predicting science commercialization outcomes.
We studied regenerative medicine commercialization activity across three research-intensive universities within three countries: the United States, the United Kingdom, and Russia.To preserve the anonymity of the UCEEs under investigation, we do not directly identify them.The UCEEs that we studied included a large US research institution and its associated UCEE (UCEE US); a large UK research institution and its associated UCEE (UCEE UK); and a large Russian research institution and its associated UCEE (UCEE Russia).We provide further information relating to the selection of UCEEs in Appendix A.

Data collection: narrative interviews
We employed a long-form narrative interview format (McCraken, 1988;Jovchelovitch and Bauer, 2000).A narrative interview approach was particularly suited to this inductive investigation since it enabled reflective meaning-making (Jovchelovitch and Bauer, 2000) and deeper theorizing (Larty and Hamilton, 2011).Selection of informants was purpose-based (Morse et al., 2002), focusing on informants that were directly involved in regenerative medicine commercialization activities and had close connections with their respective UCEE.This resulted in three categories of UCEE agents: (1) regenerative medicine entrepreneurs (ENT); (2) regenerative medicine academic scientists (AS); and (3) executive-level agents from regenerative medicine supporting entities (SEA) who were directly involved in science commercialization activities.Further information relating to the three categories of UCEE agents is provided in Appendix A.
Consistent with a narrative interview approach, target informants were asked to 'describe your role in regenerative medicine commercialization'.Across the three UCEEs, the lead author conducted 47 narrative interviews between November 2012 and May 2015.A full list of informants is reported in Table 1.

Data analysis procedures
Our data analysis began with a fine-grained review of the transcripts.The analysis involved three phases following prior inductive methods (Strauss and Corbin, 1990;Charmaz, 2006;Gioia et al., 2012).All coding was performed using NVIVO software.
Phase I. We began by carefully reviewing the transcripts, along with the field notes.Initially, we open-coded the data developing first-order codes (Strauss and Corbin, 1990).As themes emerged, we compared them both within and across transcripts, and with the field notes.Throughout this process, we were careful not to lose sight of the intact narratives and strove to preserve their depth and richness by staying close to informants' interpretations.
Phase II.We then progressed with axial-coding.This involved structuring the first-order codes into second-order themes, which relied on searching for relationships between codes and grouping them into common themes (Strauss and Corbin, 1990).We moved back and forth between our data and extant theory to develop themes that were grounded in our data but expanded upon with the help of existing concepts.During this process, we employed the constant comparative method (Glaser, 1965).
Phase III.The final phase of data analysis involved the identification of theoretical dimensions from the second-order themes.In developing these dimensions, we engaged in inductive and deductive reasoning, connecting our inductive codes and themes with extant concepts and frameworks.

Findings
Figure 1 illustrates the data structure that emerged from our analysis of the 47 narrative interviews.In Appendix B, we show 'proof' quotes (Pratt, 2008) from the interview narratives that led to the development of the second-order themes and theoretical dimensions.We discuss our findings, paying close attention to the theoretical dimensions that surface the institutional science commercialization support mechanisms, UCEE science venturing, and most importantly, UCEE agent-institution dynamics.

Institutional science commercialization support mechanisms
Commercialization support mechanisms are critical for science commercialization activities.Across the three UCEEs, we witnessed significant differences between their commercialization policies and processes.Yet, consistent across the UCEEs, was that each research institution had strong mandates to commercialize regenerative medicine.For example, the creation of purpose-built regenerative medicine centers within each UCEE, whose core mission is to foster science commercialization and translate stem cell research from the laboratory to the clinic/market, further supported institutional-wide mandates and commercialization activities.In addition, there were numerous entrepreneurial training and educational programs across the UCEEs.Some of these programs were embedded at the university-level, where we witnessed programs offered by the university's TTO or Business School.Other programs were focused at the UCEElevel and were typically overseen by state-funded innovation organizations.Additionally, each UCEE offered various platforms to support science commercialization activities.Informants talked about translational programs and proof-of-concept programs to assist regenerative medicine commercialization activities.Others talked about physical infrastructure, including platforms such as incubators or accelerators, as a support during the long gestation period.Despite these mechanisms and platforms, we observed deviances from commercialization mandates across the UCEEs, with agents in the form of some senior academics discouraging science commercialization activities -see Table 2, example A. Others spoke about institutional mandates to engage in commercialization activities as being nothing more than 'lip-service' -see Table 2, example B. This provided evidence of goal misalignment across the UCEEs, which created potential conflicts for agents engaging in commercializing activities, as highlighted in Table 2, example C. In example C, we observe a scientist-turned-entrepreneur utilizing  language (e.g., publications, research, and grant funding) that is more aligned to an academic identity rather than a commercialization-focused entrepreneurial identity.
We also witnessed preferences toward the vehicle for translational activities across the three UCEEs.Specifically, UCEE US favored spinout ventures, UCEE UK emphasized licensing, while UCEE Russia was more flexible and had no preference between spinout or licensing.These variances suggest varied UCEE priorities and/or limited commercialization options, which placed pressure on individual scientists who sought commercial pathways that differed from the intuitional norms.
In sum, our study found several contradictions across the research settings.While all UCEEs had formal mechanisms to promote science commercialization, UCEE agents' perceptions of the legitimacy of these mechanisms differed greatly for each UCEE, which had important influences on agent commercialization behavior and commercialization pathway choices.In part, commercialization activities require academic scientists to first identify any individualinstitutional conflicts toward science commercialization and then be adept at overcoming them.

UCEE science venturing
Our findings across the UCEEs revealed the uncertainties inherent to science venturing.UCEE agents consistently spoke of the ethical uncertainties and challenges surrounding regenerative medicine, which created tension with the University's TTO mission.Others spoke of regulatory uncertainties associated with regenerative medicine venturingsee Table 3, example A. At the same time, many spoke, more generally, of the institutional challenges to commercializing regenerative medicine innovations and science commercialization.The guidance provided by the university and TTO to these institutional challenges helps to form the UCEE agent-institution dynamics and commercialization pathway.
A critical element of the commercialization pathway was the regenerative medicine venture's business model.Across the UCEEs, our findings illustrate informants discussing both current and future business models.Legitimizing these business models was an important factor of the commercialization pathway within our dataset across the UCEEs.Yet, the commercialization pathway was constrained by the availability of resources.All UCEEs faced significant financial capital constraints because they operated in capital deficient institutional environments.However, resource munificence is not solely about financial capital; UCEE Russia, much like new ventures, faced significant human capital constraints, which required UCEE agents to look beyond the immediate UCEE and attract international human capital to enable science commercialization activities -see Table 3, example B. Such activities emphasize the requirement of UCEEs to have porous boundaries, where people and knowledge can ebb and flow.For science commercialization, this is imperative since life science venturing, especially in nascent markets, requires ventures to leverage knowledge capabilities within and across the UCEE.As such, and encouragingly, our findings revealed the importance of planned collaborations and partnerships as a necessary requirement and strategy for science commercialization activities.Similarly, our findings also revealed the importance of networks in fostering science commercialization within the UCEE.While some of these networks were formal and as a result of established science commercialization mandates, others were more informal, as shown in Table 3, example C. Again, in Table 3, example C, we witness a scientist-turned-entrepreneur struggling with a commercialization-focused entrepreneurial identity.

UCEE agent-institution dynamics
The idiosyncratic nature of science commercialization influenced how UCEE agents responded to institutional mandates.While we know that entrepreneurial action is driven by individual agents'

Sidestepping (UCEE UK)
Within UCEE UK, despite institutional mandates being in place to support science commercialization activities, UCEE agents repeatedly spoke about challenges and conflicts in their efforts to commercialize their regenerative medicine innovations.For example, some spoke of the institutional challenges toward science commercialization and their fear of agents leaving the UCEE, prior to even commercialization their innovations, due to these challenges: …if I look at the colleagues that I work with, they're kind of young, and they're very keen [to commercialize] to get it out there and really wanting to make a difference.But they're being stifled --so many boulders are being put in their way…I fear they will leave sooner rather than later because they feel that they can't do anything.And that is because the university is standing in their way…It's extremely frustrating!(Informant #22 -UCEE UK AS) Others focused on the misalignment of academic and commercial goals and outcomes: Part of the funding for that was on the basis that there was a commercial aspect to the activities in this building.That's slightly at odds with what the university interests are…So, you have a bit of a disconnect between the university who wanted this fantastic research facility and some of the funders who say, 'well hang on a minute, we want to commercialize it, we want to see this thing exploited.

(Informant #8 -UCEE UK SEA)
As a consequence, within UCEE UK, we observed agents acting upon the institution and sidestepping science commercialization institutional mandates to drive forwards commercial activity.Specifically, sidestepping reflects the translation of scientific innovations through political means and lobbying to change/adapt/shape existing technology transfer and commercialization structures and policies:

…we fortunately had an extremely good and influential backer…he heads up the [name of Centre], he's also Chief Executive of [name of organization], plus he's a clinician…he was keen and supportive of the idea…he was our main sponsor within the university…he said, 'if you wait for them [the
University TTO] you'll never do it,' he said 'just do it.'So, we did it, we created the company, and we did it on the basis that the university would, hopefully at due course, join the party once the venture was es-tablished…we managed to persuade them…and this was the key I guess, we persuaded them that it was in their interest or the UK's interest in developing this regenerative medicine capability.

Some three and a half years ago, the [university collaboration] initiative began… Eventually, he got made Director of [role withheld to preserve anonymity of individual]…and he said that he doesn't want to commercialize anymore! (Informant #38 -UCEE Russia AS)
As such, within UCEE Russia, we witnessed UCEE agents acting upon the institution and violating science commercialization institutional mandates to drive forward science commercialization pathways.Here, agents were translating scientific innovations by operating and engaging in science commercialization activities outside the existing technology transfer and commercialization structures and policies: …concerning the translational part, we just have to do it ourselves in Russia…the greatest challenge for us is to overcome this instability and know the rules, and to elaborate our own strategy and to find reliable industrial partners…so I have some fundamental research and that's why I have to commercialize with abroad laboratories and companies in Sweden, in US, and in the UK.(Informant #41 -UCEE Russia AS) More specifically, within UCEE Russia, we witnessed UCEE agents driving science commercialization activities through reliance on institutions external to the immediate UCEE.In essence, the UCEE was serving as a proxy: …we started to develop a collaboration with Germans and invest money…Also, we have some collaborations with a lipoxin company on the AIM in UK…we developed this drug together, with our collaborator company in the US…and together with another collaborator in Germany, developed this drug.
(Informant #37 -UCEE Russia ENT) At the same time, we witnessed a strong reliance on expertise and support from outside of UCEE Russia (particularly overseas expertise and support) since this was not available within the proximate UCEE: …It's especially important inside Russia because what we realize is that people who are doing innovations here, they feel quite alone, they still don't have strong networks…We're trying to invite people from outside…so now we have a community of mentors from US, and other countries… (Informant #40 -UCEE Russia SEA) Furthermore, there was a heavy reliance on a transplanted-in operating business model:

We are working very closely with [external US institution]…this is the mother of our model…it's a really important factor for us 'cause' we've learned most of what we've learned from [external US institution]… Every week we have a call with a Manager from [external US institution]
, who is a good friend of ours by now, and we discuss cases, approaches, their practices, how would they go around this case or that case, even policy development…we implement their principles and models here.(Informant #42 -UCEE Russia SEA) Ultimately, across the different stages of UCEE development within our dataset, we observe a range of agent-institution dynamic interactions distinct to each UCEE.These findings have important implications for science commercialization pathways.We now discuss these implications and offer possible avenues for future research.

Discussion
Taking a systems view, we extend earlier work that proposed frameworks and empirically tested conditions when entrepreneurial scientists carved out commercialization pathways under conditions of misaligned and/or limited institutional mandates (Criscuolo et al. 2014;Markman, 2015;Drivas et al., 2018;Klingbeil et al., 2019).Specifically, we discuss the idiosyncrasies of science commercialization within a UCEE, reflecting on the institutional mandates that support (or hinder) UCEE agents advancing science by undertaking commercialization activities.Since this reflects only one part of the dynamicinstitutions acting on agents -we continue our discussion to consider the second part of the dynamic -how agents act on institutions during science commercialization, which is an equally important element in determining commercial pathways since this has important implications for how UCEEs evolve.

Science commercialization within a UCEE
Our findings highlight factors that influence (i.e., positively or negatively) science commercialization at the individual, organizational, and institutional levels of analysis.At the individual agent level, our findings recognize the importance of UCEE agent behavior.We reveal tensions between how individuals interpret institutional mandates that balance teaching and research with translational activities.In doing so, we recognize the potential role-identity conflicts (Jain et al., 2009) during science commercialization, especially when the commercial path does not follow institutional norms.In some instances, we observe some entrepreneurs struggling with identity, using language more aligned to their prior role as an academic (e.g., publication process and outcomes) rather than commercialization-focused entrepreneurial language.While these scientist-turned-entrepreneurs identify themselves as 'entrepreneurs,' they may still be transitioning from a scientific identity to a commercialization-focused entrepreneurial identity (Hayter et al., 2021).In some instances, they may have not completely transitioned and retain a hybrid academic-entrepreneur identity (Jain et al., 2009), which has been shown to complement science commercialization (Wang et al., 2021).
In translating regenerative medicine innovations from laboratory to the clinic (and even the market), our findings revealed multiple discussions from UCEE agents relating to navigating business model formation and structure within the prevailing institutional mandates.The configuration of the structural elements of the venture's business model will determine how ventures pursue the entrepreneurial opportunity (George and Bock, 2011).Legitimization of the regenerative medicine venture's business model is important too (Jain and George, 2007;Bock and Johnson, 2018).
Additionally, our findings reveal the importance of individual agents in the form of human capital availability, which differed greatly across the UCEEs.Findings revealed the exodus of promising scientists and entrepreneurs in UCEE Russia.While human capital deficiencies are not a new phenomenon, such deficiencies casts doubt on innovation (Michailova et al., 2013), which is problematic for science commercialization and the development of UCEEs.Yet, agents in UCEE Russia were addressing this concern by expanding the boundaries of the UCEE; they actively recruited individuals external to the immediate UCEE, particularly returnee Russian nationals who had spent time in more developed economies, to assist in the development of knowledge capabilities, international knowledge spillovers, and social capital (Liu et al., 2010).This activity is especially important during the early stages of entrepreneurial ecosystem evolution (Schaefer, 2018).
Organizationally, prior research has highlighted how TTOs with clearer policies are better placed to support commercialization activities (Lockett et al., 2003).At the same time, those that incentivize commercialization activities foster venturing (Macho-Stadler and Pérez-Castrillo, 2010).In some instances, our findings revealed that translational activities were driven by the TTO rather than driven by market opportunities.Training for UCEE agents was one norming process TTOs employed.Recent studies have emphasized the importance of TTOs as providers of science and technology entrepreneurship education (Bolzani et al., 2021).Additionally, our findings reveal the importance of dedicated, purpose-built science commercializing centers, as well as incubators and accelerators, and their role in translational activities, emphasizing the importance of organizational infrastructure to science commercialization and UCEE evolution (Kolympiris and Klein, 2017;Clayton et al., 2018;Breznitz and Zhang, 2019;Johnson et al., 2019).
At the institutional-level, institutions can support or hinder science commercialization activity (Huyghe and Knockaert, 2015;Escobar et al., 2017).Our findings revealed that when institutional mandates supported knowledge exchange activities within and across the UCEE, increased collaborations and partnerships were observed.Our observations revealed these collaborations and partnerships to be planned strategic activities (c.f.Mintzberg and Waters, 1985).More specifically, across the UCEEs, there were differences between the emphasis placed by the institution toward encouraging and supporting knowledge exchange activities.This is important to science commercialization since knowledge exchange activities enable the development of knowledge capabilities and absorptive capacity, which are essential for venturing activities and entrepreneurial ecosystems (Alnuaimi and George, 2016;Miller et al., 2016).Yet, while institutions and institutional mandates are important to UCEE science venturing, we also recognize the importance of UCEE agent behavior in driving science commercialization.This agent-institution bi-directional relationship is important and speaks to the wider literature on institutional work (Lawrence et al., 2011), specifically the role of collective agent behaviors in institutional creation work (Farny et al., 2019).Therefore, we now turn our attention to this agent-institution bi-directional relationship.

UCEE agents and institutions:
a bi-directional relationship Second, within UCEEs that are still evolving (i.e., UCEE UK), and with perceived challenging institutional mandates toward entrepreneurship, we witness UCEE agents acting upon institutions and adapting and sidestepping institutional mandates to drive science commercialization.For the most part, this behavior is incremental in nature and does not fundamentally challenge the rules of the game.Recent research has highlighted that academics within the life sciences are more likely to bypass formal university commercialization structures (Goel and Goktepe-Hulten, 2018).While confirming individual motivation remains an empirical challenge, (i.e., bypassing formal university commercialization structures may be as a result of ignorance to these structures), in the life sciences, bypassing cannot be explained solely by a lack of knowledge toward university commercialization structures (Huyghe et al., 2016).
Third, in UCEEs at the early stages of development (i.e., UCEE Russia), we observe a fast-evolving UCEE but one with perceived institutional challenges toward science commercialization.As a consequence, we witness UCEE agents acting upon the institution by violating rules/norms and purposely avoiding the immediate UCEE to drive science commercialization activities.More specifically, agents placed a strong emphasis on both external institutions and external expertise, as well as a transplanted-in operating business model during science commercialization.Such activity reflects an attempt to create a parallel commercialization system outside of the existing UCEE, at least in the immediate term, while the UCEE further evolves.This parallel UCEE is externally legitimized and resourced and does not engage with the proximate UCEE (other than the UCEE serving as a proxy to receive and distribute financial capital).It also facilitates entrepreneurial behavior akin to bypassing (c.f.Gianiodis et al., 2016) and bootlegging (c.f.Criscuolo et al., 2014), but goes further in an attempt to completely avoid the proximate UCEE in order to successfully drive science commercialization pathways.
Further, our findings of agent behavior, and subsequent science commercialization pathways developed by influencing existing UCEE institutions, suggest important implications for the evolution of UCEEs.Enhancing our understanding of ecosystem evolution is especially timely (Dedehayir et al., 2018;Cho et al., 2021) and best observed by investigating the behaviors of multiple ecosystem agents across several ecosystems (Hakala et al., 2020;Wurth et al., 2021).Accordingly, our findings suggest that when UCEE agents align and adhere to institutional rules, norms, and mandates, this reflects an ecosystem that evolves through an engineered process (Ritala and Almpanopoulou, 2017).Yet, when ecosystems are at the early stages of evolution, it is important not to overlook the importance of ecosystem agents.For example, despite planned institutional mandates designed to engineer ecosystems in a particular way, ecosystem agents can (and do) play a critical role in shaping the direction and evolutionary pathway of the ecosystem (Lowe and Feldman, 2017;Feldman and Lowe, 2018).In particular, the entrepreneurial ecosystem co-evolves (Ritala and Almpanopoulou, 2017) as a consequence of agent behavior.Specifically, when institutional science commercialization mandates challenge venturing activity, UCEE agents can still act entrepreneurially to drive commercial activity (Lucas and Fuller, 2017).
How entrepreneurial processes influence ecosystem emergence and development remains a significant limitation to entrepreneurial ecosystem research (Spigel and Harrison, 2018).At the formative stages of the entrepreneurial process -opportunity development -ecosystem agents have been shown to engage in three distinct opportunity co-evolution phases: cointuiting, co-interpreting, and co-integrating (O'Shea et al., 2021).In our study, we build upon O'Shea et al.'s (2021) work by exploring the latter stages of the entrepreneurial process -opportunity commercialization.While O'Shea et al. ( 2021) considers potential commercialization pathways during opportunity co-evolution within entrepreneurial ecosystems, we reveal how UCEE agents enact science commercialization pathways based on their behavioral responses to science commercialization mandates (i.e., adhering, sidestepping, violating).In doing so, we highlight how UCEEs evolve based on distinct behavioral responses to science commercialization mandates.As such, we contribute to the limited research connecting (phases of) the entrepreneurial process (e.g., opportunity commercialization) to entrepreneurial ecosystems emergence (Spigel and Harrison, 2018;O'Shea et al., 2021).
From laboratory to clinic R&D Management 2022 13

Limitations and future research
As with all research, there are certain limitations to our study, which future research should address.First, the complex legal, regulatory, ethical, funding, technological, and operational uncertainties inherent to regenerative medicine commercialization (Bock and Johnson, 2018) may have unique consequences for science commercialization activities, which may be otherwise absent/different for less controversial and complex technologies.Further studies could explore other scientific fields, such as nanotechnology or synthetic biology, to observe whether we see the same behavioral responses to science commercialization mandates and UCEEs evolution.Further, our findings may not be generalizable to wider entrepreneurial ecosystems.For example, within UCEEs, entrepreneurial activities are not the sole/predominant role of universities, unlike more traditional entrepreneurial ecosystems (Canter et al., 2021).Within UCEEs, commercialization success may come at the expense of academic success (George and Bock, 2008).Future research should examine entrepreneurial ecosystems with a limited university presence to observe if our research findings hold true.
Second, ecosystems are dynamic in time and space (Canter et al., 2021).Yet, we rely on a static, cross-sectional dataset.However, during the interviews, UCEE informants did recall historic information regarding science commercialization activities within the UCEE.Related, this static focus prevents us from examining how UCEE agent behavior changes over time.Therefore, researchers should employ longitudinal methodologies that capture changes in agent behavior and organizational and institutional arrangements.This may shed light onto whether we see shifts in UCEE agent-institution dynamics.For example, future research could investigate whether we see shifts from sidestepping or violating behaviors to adhering behaviors if/when the UCEE has better science commercialization support mechanisms in place.This will build upon recent work exploring the role of agency and institutional creation work (Farny et al., 2019).
Third, given that, ultimately, the end goal for the different actors was the commercialization of a stem cell innovation, we dealt with the three different groups of UCEE agents in our study as a collective since all had the same end goal in sight.Therefore, we should be mindful that our findings are not specific to each distinct agent role.At the same time, we should be mindful that our dataset includes some scientistturned-entrepreneurs.Our findings hint toward these agents taking a hybrid scientist-entrepreneur identity (Jain et al., 2009;Hayter et al., 2021), which warrants further investigation prior to generalizing our findings more broadly to entrepreneurial agency.Further research should explore these different UCEE agents in further detail, perhaps developing psycho-social models of individual behavior.

Conclusion
Our study examined agent-institutional dynamics during science commercialization activities and represents an important step forward in our understanding of entrepreneurial behavior within UCEEs.We reveal the idiosyncrasies of science commercialization activities across three UCEEs at differing stages of development.First, by investigating science commercialization within a UCEE, as well as exploring agent-institution dynamics, we address both the limitations of uni-level studies and studies that fail to consider the bi-directional relationship between agents and institutions.In our study, by adopting a multilevel approach and investigating how institutions act on agents and how agents act on institutions, we close this gap in the literature.In doing so, we reveal important implications for UCEE evolution.From a policy perspective, this is important since it reveals the need to align institutional science commercialization mandates to agent entrepreneurial behaviors, motivations, and intentions.Doing so may prevent the unintended outcome of bypassing (Gianiodis et al., 2016) or bootlegging (Criscuolo et al., 2014).
Second, by taking a microfoundations approach, we demonstrate the behavioral responses of UCEE agents to institutional expectations and pressures.Specifically, we capture the nuances of the science commercial mode choice -how UCEE agents seek possible commercial pathways given perceived benefits and limits in their institutional environment.This finding has policy implications; crafting strong yet flexible institutions that better align individual interests are likely to prevent UCEE agents from enacting extraordinary quasi-institutions.

Richard T. Harrison is Emeritus Professor of
Entrepreneurship and Innovation at the University of Edinburgh Business School.He researches the nature of the entrepreneurial process -in social, corporate, and new venture settings -as it is reflected in business development (particularly in the financing by business angels and VCs, of innovation and growth), and in the implications of research theorizing for practice and public policy.
Adam J. Bock is a Lecturer at the Wisconsin School of Business, University of Wisconsin-Madison.He is also a venture financier and serial entrepreneur.As an academic, he studies entrepreneurship, business models, and technology venturing.Bock has co-founded four life science companies spun out of university research.
APPENDIX A Additional information relating to the selection of UCEEs and UCEE agents We chose our research settings based on three criteria: first, given that the formation of UCEEs is a global phenomenon, we wanted a sample of UCEEs across multiple countries.Second, we wanted different types of universities -that is, driven by both explicit and implicit missions and strategies.Third, we required UCEEs to span different stages of regenerative medicine commercialization activity.
We began our search of appropriate research contexts by investigating UCEEs with dedicated stem cell research centers/institutes.Complementing this search, we studied stem cell/regenerative medicine patent data, and journal and news articles, to catalog UCEEs that were active in regenerative medicine commercialization.Our search surfaced many suitable UCEEs from across the globe.From this sample frame, we selected three institutions where the authors had current relationships, which could contribute to a secured access to the different agents operating in the UCEEs.
Each of the UCEEs under investigation have sufficient similarities (e.g., a dedicated stem cell center/institute, world renown scientists, etc.) and differences (e.g., at different stages of regenerative medicine commercialization, level of endowed resources, etc.), in addition to being geographically dispersed.Of the three locations, the UCEE US has the longest history of regenerative medicine commercialization.The UCEE UK reflects a UCEE that has a less established history of regenerative medicine commercialization in comparison to UCEE US.Finally, UCEE Russia, while less established than the other two UCEEs, was created with a key strategic focus to foster an entrepreneurial ecosystem.
Within our dataset, the entrepreneurs were founders of regenerative medicine spinouts from the respective university but also included more established ventures that were connected to the UCEE in some way.For example, some of the more established ventures were operating from the university science park, while others had technologies through research collaborations with the university.Some of the entrepreneur informants were prior academic scientists, as indicated in Table 1.All the academic scientists were Principal Investigators operating out of the stem cell labs of the university.Support entities were either directly linked to the university (i.e., the university TTO) or operated closely with the university (i.e., provided regional support for stem cell scientists and entrepreneurs).This support ranged from grants for research and/or venturing activities, business training, assistance with industry collaborations, and/or assistance in connecting the scientists and ventures with investors.Additionally, support entities included venture capitalist firms and angel investor networks.We interviewed senior executives from these support entities.
Johnson is an Assistant Professor in Entrepreneurship at the Adam Smith Business School, University of Glasgow.His research explores university-centered entrepreneurial ecosystems, science-based entrepreneurship, technology transfer, and academic entrepreneurs.Peter T. Gianiodis is a Professor of Strategy and Entrepreneurship at the Palumbo Donahue School of Business, Duquesne University and the inaugural holder of the Merle E. Gilliand Professor in Entrepreneurial Finance.Gianiodis' research explores market entry across several contexts, including new venture entry into mature markets, and technology commercialization from university start-ups.

Table 1 .
Informant information 1 AS: Academic Scientist; ENT: Entrepreneur; SEA: Support Entity Agent.2Indicatesinstances where the entrepreneur was a prior academic scientist.

Table 2 .
Institutional science commercialization support mechanisms: UCEE agent quotes A'…I find that extremely difficult to encourage…spinouts take a lot of time and a huge amount of work… academics are judged by their papers and grants, not commercial activities.(Informant#9 -UCEE UK AS) B '…they have funded very significantly our research and we could take this research into the clinic…it is surprising because we have everything, we have all the technology to create, for example, tissue banks, skin banks, or draft banks…and I do not know why they do not want to help commercialize, I cannot answer this question…they have funds and the policies, but they do not support the commercialization of this scientific work.' (Informant #41 -UCEE Russia AS) C'…And I view that as being critical because the way that our scientific environment is structured, we publish papers, research, and get proposals funded…we cannot have impact…we are unable to commercialize fundamental discoveries…' (Informant #33 -UCEE US ENT)

Table 3 .
UCEE science venturing: UCEE agent quotes countries and ask if they have the possibility to come work here in Russia.We go to States, to Germany, to Holland…we need these guys to have advantage in this technology.'(Informant #39 -UCEE Russia ENT) C 'I've been going to as many of the informal local entrepreneurial network meetings.You know, trying to meet people…to kind of get some insight as to what it takes.It's still a foreign world to me 'cause' none of my training to this point has been in this area (entrepreneurship).' (Informant #26 -UCEE US ENT) …She really urged me to talk to [The TTO] and file an IDR…I talked with them…they were so support-ive…they're like, 'Yes, file something.You know, this is really cool.'And so, I put it in, and they said, 'we want to move this forward,' and I feel like all of a sudden, I have this opportunity that is not likely going to happen elsewhere.(Informant #25 -UCEE US ENT)