The long-term success of surgical repair of rotator cuff tears is largely dependent on restoration of a functional tendon-to-bone interface. We implemented micro-precise spatiotemporal delivery of growth factors in three-dimensional printed scaffolds for integrative regeneration of a fibrocartilaginous tendon-to-bone interface. Sustained and spatially controlled release of tenogenic, chondrogenic and osteogenic growth factors was achieved using microsphere-based delivery carriers embedded in thin membrane-like scaffolds. In vitro, the scaffolds embedded with spatiotemporal delivery of growth factors successfully guided regional differentiation of mesenchymal progenitor cells, forming multiphase tissues with tendon-like, cartilage-like and bone-like regions. In vivo, when implanted at the interface between the supraspinatus tendon and the humeral head in a rat rotator cuff repair model, these scaffolds promoted recruitment of endogenous tendon progenitor cells followed by integrative healing of tendon and bone via re-formation of strong fibrocartilaginous interfaces. Our findings demonstrate the potential of in situ tissue engineering of tendon-to-bone interfaces by endogenous progenitor cells. The in situ tissue engineering approach shows translational potential for improving outcomes after rotator cuff repair.
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http://dx.doi.org/10.1088/1758-5090/ab48ca | DOI Listing |
Nat Methods
January 2025
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries.
View Article and Find Full Text PDFCryobiology
January 2025
ICAR-National Bureau of Plant Genetic Resources, New Delhi-110 012 INDIA.
Ex situ conservation of plant genetic resources (PGR) plays a crucial role in sustainable growth and development, as highlighted by the Global Strategy for Plant Conservation (GSPC). Seed genebanks, a key component of ex situ conservation, have been instrumental in preserving plant diversity. However, challenges arise with the conservation of non-orthodox (recalcitrant and intermediate) seeds and vegetative tissues, which are not amenable to storage in traditional genebanks at temperatures of -20°C.
View Article and Find Full Text PDFStroke
February 2025
Neurovascular Research Unit, Pharmacology Department, Complutense Medical School, Instituto Investigación Hospital 12 Octubre, Madrid, Spain (G.D., B.D., A.M., J.M.P., I.L.).
Background: Acute ischemic stroke treatment typically involves tissue-type plasminogen activator (tPA) or tenecteplase, but about 50% of patients do not achieve successful reperfusion. The causes of tPA resistance, influenced by thrombus composition and timing, are not fully clear. Neutrophil extracellular traps (NETs), associated with poor outcomes and reperfusion resistance, contribute to thrombosis.
View Article and Find Full Text PDFCureus
December 2024
Department of Breast, Plastic and Reconstructive Surgery, Royal Hallamshire Hospital, Sheffield, GBR.
Background The incidence of margin re-excision following breast conserving surgery (BCS) is a quality measure in the National Health Service. The threshold is less than 20% of all BCS procedures. Despite three decades of studies and a wealth of literature identifying multiple factors associated with increased risk for margin involvement, an accepted threshold rate affecting one in five procedures remains high.
View Article and Find Full Text PDFMater Today Bio
February 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
Inspired by the initial mineralization process with bone matrix vesicles (MVs), this study innovatively developed a delivery system to mediate mineralization during bone regeneration. The system comprises nanofibrous chitosan microspheres (NCM) and poly (allylamine hydrochloride)-stabilized amorphous calcium phosphate (PAH-ACP), which is thereafter referred to as NCMP. NCM is synthesized through the thermal induction of chitosan molecular chains, serving as the carrier, while PAH-ACP functions as the mineralization precursor.
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