Abstract

The socioeconomic impact of osteochondral (OC) damage has been increasing steadily over time in the global population, and the promise of tissue engineering in generating biomimetic tissues replicating the physiological OC environment and architecture has been falling short of its projected potential. The most recent advances in OC tissue engineering are summarised in this work, with a focus on electrospun and 3D printed biomaterials combined with stem cells and biochemical stimuli, to identify what is causing this pitfall between the bench and the patients’ bedside. Even though significant progress has been achieved in electrospinning, 3D-(bio)printing, and induced pluripotent stem cell (iPSC) technologies, it is still challenging to artificially emulate the OC interface and achieve complete regeneration of bone and cartilage tissues. Their intricate architecture and the need for tight spatiotemporal control of cellular and biochemical cues hinder the attainment of long-term functional integration of tissue-engineered constructs. Moreover, this complexity and the high variability in experimental conditions used in different studies undermine the scalability and reproducibility of prospective regenerative medicine solutions. It is clear that further development of standardised, integrative, and economically viable methods regarding scaffold production, cell selection, and additional biochemical and biomechanical stimulation is likely to be the key to accelerate the clinical translation and fill the gap in OC treatment.

Highlights

  • It uses allogeneic articular cartilage (AC) harvested from juvenile donors and divided into chondral fragments that are secured into focal cartilage defects in a single-stage procedure using fibrin adhesive [43,46]

  • While the chondral section should resemble the native AC with its dense ECM of collagen type II fibres and hyaluronic acid molecules organised along the different AC sublayers, the osseous section should replicate the complex micro/nano anatomical bone structure including the nanoscale hydroxyapatite composites deposited along the collagen type I bundles

  • Such combinatory approaches may be of particular interest for osteochondral tissue engineering (OCTE), enabling the simultaneous delivery of factors involved in both subchondral bone (SB) and AC repair [155,156,157], even though obtaining positive results with dual growth factor delivery may not be straightforward [158,159]

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Summary

Osteochondral Damage

Synovial or diarthrodial joints comprise most of the body’s articulations and are characterised by wide ranges of near-frictionless motion, as well as load transferring capabilities during weight-bearing [1]. In these joints, two articulating bones glide smoothly through each other due to the presence of a composite system known as the osteochondral (OC) unit. There is healthy homeostatic crosstalk between cartilage and bone that leads to regulated tissue remodelling and joint integrity maintenance [6]. Upon any damage, joint homeostasis is disturbed, and a catabolic unhealthy crosstalk is developed, leading to dysregulated bone remodelling, imbalanced cartilage regulation and progressive OC degeneration [8]. Traumatic injuries and degenerative diseases (usually associated with ageing, inflammatory disorders and underlying genetic predisposition) account for the most common causes of OC damage [9,10]

Aetiology and Epidemiology
Current Therapies
The Need for Improved Osteochondral Regenerative Solutions
Osteochondral Unit
Articular Cartilage
Cartilage–Bone Interface
Subchondral Bone
Osteochondral Tissue Engineering
Incorporation of Biochemical Stimuli
Building Block Assembly
Electrospinning
Additive Manufacturing
From Practice Back to Theory
Findings
Conclusions
Full Text
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