Native tissue structures possess elaborate extracellular matrix (ECM) architectures that inspire the design of fibrous structures in the field of regenerative medicine. We review the literature with respect to the successes and failures, as well as the future promise of biopolymer microthreads as scaffolds to promote endogenous and exogenous tissue regeneration. Biomimetic microthread tissue constructs have been proposed for the functional regeneration of tendon, ligament, skeletal muscle, and ventricular myocardial tissues. To date, biopolymer microthreads have demonstrated promising results as materials to recapitulate the hierarchical structure of simple and complex tissues and well as biochemical signaling cues to direct cell-mediated tissue regeneration. Biopolymer microthreads have also demonstrated exciting potential as a platform technology for the targeted delivery of stem cells and therapeutic molecules. Future studies will focus on the design of microthread-based tissue analogs that strategically integrate growth factors and progenitor cells to temporally direct cell-mediated processes that promote enhanced functional tissue regeneration.

A challenge for the design of scaffolds in tissue engineering is to determine a terminal sterilization method that will retain the structural and biochemical properties of the materials. Since commonly used heat and ionizing energy-based sterilization methods have been shown to alter the material properties of protein-based scaffolds, we evaluate the effects of ethanol and ethylene oxide (EtO) sterilization on the cellular compatibility and the structural, chemical, and mechanical properties of uncrosslinked, UV crosslinked, or carbodiimide crosslinked fibrin microthreads in neutral (EDCn) or acidic (EDCa) buffers. EtO sterilization significantly reduces the tensile strength of uncrosslinked microthreads. Surface chemistry analyses show that EtO sterilization induces alkylation of EDCa microthreads leading to a significant reduction in myoblast attachment. The material properties of EDCn microthreads do not appear to be affected by sterilization method. These results significantly enhance the understanding of how sterilization or crosslinking techniques affect the material properties of protein scaffolds.

ObjectiveEvaluation of early compositional changes in healing articular cartilage is critical for understanding tissue repair and for therapeutic decision-making. Fourier transform infrared imaging spectroscopy (FT-IRIS) can be used to assess the molecular composition of harvested repair tissue. Furthermore, use of an infrared fiber-optic probe (IFOP) has the potential for translation to a clinical setting to provide molecular information in situ. In the current study, we determined the feasibility of IFOP assessment of cartilage repair tissue in a rabbit model, and assessed correlations with gold-standard histology.DesignBilateral osteochondral defects were generated in mature white New Zealand rabbits, and IFOP data obtained from defect and adjacent regions at 2, 4, 6, 8, 12, and 16 weeks postsurgery. Tissues were assessed histologically using the modified O’Driscoll score, by FT-IRIS, and by partial least squares (PLS) modeling of IFOP spectra.ResultsThe FT-IRIS parameters of collagen content, proteoglycan content, and collagen index correlated significantly with modified O’Driscoll score (P = 0.05, 0.002, and 0.02, respectively), indicative of their sensitivity to tissue healing. Repair tissue IFOP spectra were distinguished from normal tissue IFOP spectra in all samples by PLS analysis. However, the PLS model for prediction of histological score had a high prediction error, which was attributed to the spectral information being acquired from the tissue surface only.ConclusionThe strong correlations between FT-IRIS data and histological score support further development of the IFOP technique for clinical applications, although further studies to optimize data collection from the full sample depths are required.

Introduction The global increase in number in severity of traumatic and degenerative musculoskeletal diseases affects the quality of life and increases health-care costs and resource expenditure. Facing an epidemic of orthopaedic tissue pathology in all ages and economic surroundings, modern medicine is challenged to improve strategy to deliver efficient and affordable treatments. Regenerative medicine has been identified as able to offer revolutionary solutions and to enable complete structural and functional rehabilitation of tissues, organs and bodily systems. This article reviews current regenerative medicine strategies for musculoskeletal diseases of bone, tendon and cartilage, which made their way to clinical application. Stage-related disease regenerative medicine planning and phenotypic mesenchymal stem cell biomarker characterisation are identified as potential factors accelerating the clinical applicability of mesenchymal stem cell-based therapies for musculoskeletal regeneration. Conclusion Cell source profiling using biomarkers for proliferation and differentiation towards the desired lineage would be the next step in improving the regenerative medicine strategy.

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