Aims. The success of anterior cruciate ligament reconstruction (ACLR)
depends on osseointegration at the graft-tunnel interface and intra-articular
ligamentization. Our aim was to conduct a systematic review of clinical
and preclinical studies that evaluated biological augmentation of
graft healing in ACLR. . Materials and Methods. In all, 1879 studies were identified across three databases.
Following assessment against strict criteria, 112 studies were included
(20 clinical studies; 92 animal studies). . Results. Seven categories of biological interventions were identified:
growth factors, biomaterials, stem cells, gene therapy, autologous
tissue, biophysical/environmental, and pharmaceuticals. The methodological
quality of animal studies was moderate in 97%, but only 10% used
clinically relevant outcome measures. The most interventions in
clinical trials target the graft-tunnel interface and are applied
intraoperatively. Platelet-rich plasma is the most studied intervention,
but the clinical outcomes are mixed, and the methodological quality
of studies was suboptimal. Other biological therapies investigated
in clinical trials include: remnant-augmented ACLR; bone substitutes;
calcium phosphate-hybridized grafts; extracorporeal
Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article: