Engineering Spatiotemporal Osteochondral Tissue Formation with Tunable 3D-Printed Scaffolds
使用可调谐 3D 打印支架工程设计时空骨软骨组织形成
基本信息
- 批准号:10629168
- 负责人:
- 金额:$ 19.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:3D PrintAddressAdultAffectAgeAmericanBMP2 geneBindingBiochemicalBiocompatible MaterialsBone MarrowCartilageCartilage injuryCell Culture TechniquesCellsChemistryChondrocytesChondrogenesisClinicalClinical EngineeringCuesDefectDegenerative polyarthritisDepositionDevelopmentDiseaseEarly treatmentEconomic BurdenEngineeringEventFibrocartilagesGrowth FactorHealthcare SystemsHumanImplantIn SituIn VitroInferiorInkInterventionJointsLifeLocationMechanicsMedicareMedicineMesenchymal Stem CellsNatural regenerationOperative Surgical ProceduresOrthopedicsOsteoblastsOsteogenesisOutcomePainPathologyPatientsPeptidesPolymersProteinsQuality of lifeReactionRepeat SurgeryReplacement ArthroplastyResearchResolutionSecond Look SurgerySurfaceTechniquesTestingTherapeuticTimeTissue EngineeringTissue constructsTissuesTransforming Growth Factor betaTransforming Growth FactorsUnited StatesWorkadult stem cellarticular cartilagebiodegradable scaffoldbonecartilage developmentcartilage regenerationcartilage repairclinically relevantdebilitating paindesigndrug discoveryfunctional improvementhuman old age (65+)improvedin vitro Modelinnovationjoint destructionjoint functionknowledge integrationosteochondral tissueosteogenicpatient mobilitypeptidomimeticspreventprogramsrepairedreplacement tissueresponsescaffoldspatiotemporalstem cell differentiationstem cellssuccess
项目摘要
PROJECT SUMMARY
Osteoarthritis is a degenerative joint disease that affects 70% of adults over age 65, but the initial cartilage injury
usually occurs much earlier in life. Progressive joint degeneration during adulthood continues because cartilage
has very limited ability to self-repair. Current surgical interventions to repair cartilage defects at early stages
result in low quality tissue with limited long-term success. The new tissue degrades over time, which increases
exposure of the underlying bone and leads to debilitating pain. Many patients ultimately seek relief through total
joint replacement to regain mobility and improve quality of life. However, over half of all joint replacement patients
in the United States are under age 65. These younger patients are expected to outlive their implants and may
require one or more revision surgeries over their lifetime. This places a significant burden on the healthcare
system, especially the Medicare program.
The objective of this project is to develop a promising biomaterials-based approach that addresses a persistent
challenge in orthopaedic medicine—the need for long-lasting treatments for early-stage cartilage defects. This
work involves an innovative combination of 3D printing and biomaterials design to fabricate biodegradable
scaffolds for functional cartilage repair. To achieve this, the scaffolds are engineered to guide regeneration of
the entire osteochondral tissue to improve bone-cartilage integration and durability. Scaffolds will be fabricated
by 3D printing polymer-based “inks” that include special chemistries to localize specific biochemical cues called
peptides. These peptides can be designed to direct formation of bone or cartilage tissue. The inks will be spatially
deposited using 3D printing to create distinct bone-promoting and cartilage-promoting regions within a
continuous construct. Notably, the bioactive peptides can be introduced over time to mimic compositional
changes that occur during articular cartilage development.
The proposed research plan includes two specific aims designed to study how human mesenchymal stem cells
(adult stem cells found in bone marrow) respond to scaffolds presenting bone-promoting and cartilage-promoting
peptides. We hypothesize that spatially presenting these peptides over time to mimic events that occur during
development will promote stable osteochondral tissue formation. The first aim will investigate how modifying the
presentation of these peptides over time in the presence of stem cells influences their differentiation, or transition,
into bone-like or cartilage-like states. The second aim will examine how spatially presenting both peptides in the
same scaffold guides local stem cell differentiation into bone-like and cartilage-like tissue regions. The proposed
approach is powerful because it exploits high-resolution 3D printing to produce scaffolds with highly tunable
compositions designed to direct osteochondral interface regeneration. This is a key requirement for long-term
functional cartilage repair. This work will lead to breakthroughs in the ability to engineer clinically relevant tissue
replacements that prevent the onset or debilitating progression of osteoarthritis.
项目总结
项目成果
期刊论文数量(0)
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{{ truncateString('Lesley W Chow', 18)}}的其他基金
Engineering Spatiotemporal Osteochondral Tissue Formation with Tunable 3D-Printed Scaffolds
使用可调谐 3D 打印支架工程设计时空骨软骨组织形成
- 批准号:
10373762 - 财政年份:2022
- 资助金额:
$ 19.25万 - 项目类别:
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