Decellularized extracellular matrix scaffolds and biological constructs as a paradigm shift in orchestrating recapitulative tissue regeneration for complex hand reconstruction

Abstract

The inherent limited regenerative capacity of composite tissues in the human hand, frequently compromised by trauma, oncological resection, or degenerative pathologies, presents a formidable challenge in restorative surgery. Conventional autografts are constrained by donor site morbidity, finite availability, and suboptimal structural integration, while synthetic implants often fail to provide the requisite biological cues for true histogenesis. This has precipitated a translational pivot towards bioengineered strategies leveraging decellularized extracellular matrix (dECM) scaffolds. These biological frameworks, derived from allogeneic or xenogeneic tissues, are meticulously processed to remove immunogenic cellular antigens while preserving the intricate ultrastructural architecture and native bioactive signaling molecules, including glycosaminoglycans, proteoglycans, and conserved growth factors. Upon implantation, these biomimetic scaffolds act as instructive three-dimensional blueprints, facilitating host cell recruitment, proliferation, and spatially organized differentiation—a process known as guided tissue regeneration.  Critical applications in hand surgery include the use of dECM nerve conduits for bridging digital nerve gaps, chondrogenic scaffolds for articular cartilage restoration in the metacarpophalangeal and interphalangeal joints, and tendon augmentation grafts. Furthermore, the advent of bioprinting and organoid culture technologies enables the pre-seeding of these scaffolds with autologous progenitor cells, such as mesenchymal stem cells or tenocytes, creating advanced tissue-engineered constructs. The overarching objective is to transcend mere mechanical repair and achieve true biological integration and functional restitution, thereby restoring the intricate biomechanics and sensorimotor repertoire of the human hand. This manuscript will elucidate the foundational science of dECM scaffolds, delineate their current clinical applications in hand surgery, and discuss the translational hurdles and future trajectories of this burgeoning field.