A scaffold-free, collagen-guided self-assembling adipose construct for functional soft tissue reconstruction

Area of Science:

• Biomaterials Engineering
• Tissue Engineering
• Plastic and Reconstructive Surgery

Background:

• Autologous fat grafting for soft tissue defects often results in poor volume retention and slow vascularization.
• Current biomaterial strategies face challenges with biocompatibility, foreign-body responses, and limited integration.
• A need exists for improved, scaffold-free adipose constructs with enhanced regenerative potential.

Purpose of the Study:

• To develop and characterize a collagen-guided, self-assembling adipose construct (SAF) from clinical lipoaspirate.
• To investigate the effects of exogenous collagen supplementation (SAF⁺) on construct properties and regenerative capacity.
• To elucidate the underlying molecular mechanisms of collagen-driven adipose tissue self-assembly and repair.

Main Methods:

• Utilized clinical lipoaspirate to create self-assembling adipose constructs (SAF) driven by intrinsic type I collagen crosslinking.
• Supplemented constructs with exogenous type I collagen (SAF⁺) to enhance mechanical and biological properties.
• Conducted in vitro studies for adipogenic differentiation and stem cell recruitment, and in vivo studies for tissue repair, angiogenesis, and macrophage polarization.
• Investigated the role of the integrin α2β1-FAK/Src signaling pathway.

Main Results:

• SAF⁺ constructs demonstrated enhanced stiffness, elasticity, and resilience compared to SAF.
• In vitro, SAF⁺ promoted adipogenic differentiation and stem cell recruitment.
• In vivo, SAF⁺ significantly accelerated tissue repair, M2 macrophage polarization, angiogenesis, and stem cell homing.
• The integrin α2β1-FAK/Src pathway was identified as a key mediator of these regenerative effects.

Conclusions:

• Collagen-guided self-assembly provides a scaffold-free strategy for engineering stable adipose constructs.
• SAF⁺ enhances mechanical properties and promotes a pro-regenerative microenvironment for soft-tissue repair.
• This autologous approach offers improved handling, stability, and translational potential, bypassing limitations of synthetic scaffolds.