"Introduction: Soft tissue-engineered constructs (sTECs) require tailored dynamic changes in their structure-properties-process (SPP) relations to preserve their functionality throughout the tissue regenerative process. At the initial stages of regeneration, a highly interconnected architecture is recommended to accelerate plaque adhesion and blood clot formation. At later stages of regeneration, a dense lattice structure is not entirely needed whereas a mechanically supportive structure with a greater extent of free space for newly formed tissue is recommended to avoid bridging and capsular contraction. Mechanical stability of sTECs, which plays a critical role in minimizing load transfer to new tissue, should remain until subsequent remodelling stages occur. Otherwise, at the cellular level, excessive stress and strain inhibit cell proliferation and differentiation, and at the tissue level, the lack of a physical substrate to withstand external loads leads to incomplete, inadequate and compromised large volume regeneration. Another positive impact of long-term mechanical integrity is enhancing shape retention of the structure and facilitating tissue formation towards complex anatomical shapes, especially in a large scale where larger tractional forces exist. Lack of attention to these SPP relations is one of the underlying reasons for failure of sTECs in large tissue volumes where complex inter-scale relations between mechanics, biology and topology exist. This study aims to establish a transplantable workflow from materials to design, optimization, and manufacturing in an effort to tailor and customize structural/mechanical properties and behaviours for sTECs under different loading conditions.
Methods: Based on well-understood properties of new medical-grade polymers, novel rational design strategies were established to modulate the local degradation profile of composite structures and address required SPP relations essential for sustained large-volume soft tissue regeneration. Programming-assisted dual printing was utilized to deposit materials in pre-designed patterns and go beyond bulk properties of single-material structures. Comprehensive in vitro and in vivo analyses were performed on non-degraded and degraded composites.
Results: The design-dependent workflow allowed to locally tune the degradation profile of the composites and address long-term mechanical stability and shape retention to minimize excessive external loads applied to newly formed tissue at early as well as later stages of regeneration. It also allowed modulating an increase in mechanical compliance and free volume expansion which respectively led to a higher compliant deformation as well as larger free spaces for growing tissue. The other highlighted outcome of this platform was a controllable tissue guidance pathway and subsequently, organized tissue and blood vessels formation within the expanded pores which appears to support later stages of tissue formation and angiogenesis.
Conclusion: Multi-material printing of medical-grade polymers combined with rational design strategies and well-understood material properties provides a transplantable customization pathway to develop multi-functional scaffolds with tailored structural-mechanical properties which address multifaceted challenges associated with large-volume soft tissue regeneration. The proposed methodologies open new windows towards sustained large-volume soft tissue regeneration."