Multiscale Design and Synthesis of Bioinspired Protein/Mineral Systems
Guo, Jin.
2018
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Abstract: Natural
systems often outperform synthetic materials for their heterogeneous hierarchical
architectures. These biological composites are usually comprised of soft and hard phases
in complex pattern and structures, with dimension ranging from nanoscale to macroscale,
although built in ambient environments from limited components. The resulting systems
enable distinct integration of ... read morestrength and toughness, leading to elegant structures
with tissue-specific functions. For example, continuous macroscale gradients present at
the osteochondral tissue interface with nano-/micro-scale patterns, reflect complex
biological functions and involve changes in extracellular matrix (ECM) composition, cell
types and mechanical properties. To mimic these natural gradient hierarchical
architectures, this dissertation provides bioinspired mineralization strategies to
create novel protein/mineral composite systems via hierarchical assembly of
nano-building blocks onto polymeric templates. Silk protein-based composites, coupled
with selective peptides R5 with mineralization domains, were created to mimic the
soft-to-hard transition in osteochondral interfaces. The gradient composites supported
continuous transition in composition and structural and mechanical properties
corresponding to the spatial concentration gradient of the mineralization domains. The
biocompatible and biodegradable gradient silicified silk/R5 composites promoted and
regulated osteogenic and chondrogenic differentiation of human mesenchymal stem cells in
an osteoinductive and chondroinductive environment in vitro, respectively, in a manner
consistent with the cellularity and ECM gradients at osteochondral interfaces. In
addition, natural composites are usually complex and anisotropic at the microscopic
scale. Well-designed micropatterns present in native tissues and organs involve changes
in ECM compositions, cell types and mechanical properties to reflect complex biological
functions. However, the design and fabrication of these micropatterns in vitro to meet
task-specific biomedical applications remains a challenge. In this dissertation, I also
present a de novo design strategy to code bio-functional micropatterns to engineer cell
alignment through integration of aqueous-peptide inkjet printing and site-specific
biomineralization. Inkjet printing allows for the direct writing of macroscopic R5
peptide patterns with microscale resolution on the surface of silk hydrogels. This is
combined with in situ biomineralization of the R5 peptide for site-specific growth of
silica nanoparticles on the micropatterns, while avoiding the use of harsh chemicals or
complex processing. The resulting mineralized micropatterned systems were used to align
human mesenchymal stem cells and bovine serum albumin in vitro. In conclusion, this
dissertation explored the feasibility of using silk as a template to combine selective
mineralization domains to mimic the hierarchical architecture in biological systems from
the molecular level to microscale and ultimately macroscale. The bioinspired multiscale
design of mineral assembles on polymeric templates offers a useful approach to develop
complex heterogeneous organic/inorganic composites for a wide range of applications in
tissue engineering and regenerative medicine, especially osteochondral tissue
engineering.
Thesis (Ph.D.)--Tufts University, 2018.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: David Kaplan.
Committee: Gordana Vunjak-Novakovic, Qiaobing Xu, and Ayse Asatekin.
Keyword: Chemical engineering.read less - ID:
- j3860k041
- Component ID:
- tufts:24966
- To Cite:
- TARC Citation Guide EndNote
