The David Kaplan Lab
Biomaterials Engineering & Regenerative Medicine
Our focus is on biopolymer engineering to understand structure-function relationships, with emphasis on studies related to self-assembly, biomaterials engineering and regenerative medicine. His lab has extensively studied silk-based biomaterials in regenerative medicine, starting from fundamental studies of the biochemistry, molecular biology and biophysical features of this novel class of fibrous proteins. These studies have led to inquiries into the impact of silk biomaterials on stem cell functions and complex tissue formation. The result has been the emergence of silk as a new option in the degradable polymer field with biocompatibility, new fundamental understanding of control of water to regulate structure and properties, and new tissue-specific outcomes with silk as scaffolding in gel, fiber, film or sponge formats. Additional technological directions in optics, electronics, adhesives and many related areas have emerged from these studies.
Figure 1. Biomimetic processing of silk protein to produce new materials and devices. The image depicts processing of natural materials and illustrates the various uses of these materials.
The group has a longstanding interest in the study of biopolymers (structural proteins, polysaccharides), particularly the use of biological approaches to the synthesis and modification of these material systems. Genetic engineering and metabolic engineering strategies are employed to control chemistry and thus function, along with selective chemical modifications. Materials science and engineering approaches are utilized to explore structure-function relationships from processing. Questions of self-assembly, biological interfaces and degradation are studied, along with utility in cell and tissue systems. Specific polymers of interest include: silks (silkworm, spider), collagens, resilin, elastins, bacterial cellulose.
Figure 2. Fibrous proteins in nature that can be used to fabricate new materials.
The group takes a multi-fold approach to the challenges of tissue regeneration. Traditional biochemical factors are utilized to direct stem cell and tissue outcomes in selective (temporal, regional, interfacial) approaches. In addition, a major focus is on biophysical factors (membrane potential Vmem, external electric fields, mechanical forces) on cell and tissue outcomes. The orchestrated suite of inputs to cell and tissue functions is considered towards desired fundamental goals, for building quantitative metabolic models of tissue functions and regeneration in vitro, and to generate useful tissue systems for in vitro study and in vivo utility. Example tissues under study: bone, cartilage, small diameter vasculature, neurological tissues, cervical, kidney, adipose, among others.
Figure 3. Silk scaffolds can be used to produce tissue engineered bone. The figure illustrates the generation of tissue engineered bone using silk scaffolds.
Developing Tissue-based Disease Models
The two categories above (tissue regeneration, biopolymers) are exploited to develop human tissue models for relevance to the study of disease mechanisms as well as for therapeutic screening. These systems are designed to account for complex cell mixtures, vascular needs and relevant cell types to recapitulate structure and functional features of the target tissue, as well as sustainability of these tissues over extended time frames (weeks to months) for use in both acute and chronic drug screens. Example disease systems under study include: kidney, breast, prostate, obesity, diabetes, among others.
Figure 4. Application of tissue engineering to diseases affecting the eye. The illustration depicts the generation of corneas using tissue engineering techniques.
Silk-based drug delivery systems are studied to exploit the all-water processing, the ability to regulate beta sheet (crystalline) content for control of lifetime in vivo (days to years), to control medical device format (e.g., coating, fibers, tablets, gels, etc.), to deliver small or large molecules that are hydrophilic or hydrophobic, and to exploit the stabilization influence of silk on labile compounds. We approach the challenge from both a fundamental design approach (genetically engineered block copolymers) to direct delivery systems from reprocessed silkworm silk. In vitro and in vivo studies are conducted to understand and optimize the various systems.
Figure 5. Bioengineered silk-based delivery systems. The illustration depicts silk-based fibers that can be used to deliver genes to cells.