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Scott J Hollister

Publications and source records attributed to Scott J Hollister.

12 recordsLinked to original sources
PubMed2006

Framework for optimal design of porous scaffold microstructure by computational simulation of bone regeneration.

In bone tissue engineering using a biodegradable scaffold, geometry of the porous scaffold microstructure is a key factor for controlling mechanical function of the bone-scaffold system in the regeneration process as well as after the regeneration. In this study, we propose a framework for the optimal design of the porous scaffold microstructure by three-dimensional computational simulation of bone tissue regeneration that consists of scaffold degradation and new bone formation. The rate of scaffold degradation due to hydrolysis, that leads to decrease in mechanical properties, was simply assumed to relate to the water content diffused from the surface to the bulk material. For the new bone formation on both bone and scaffold surfaces, the rate equation of trabecular surface remodeling driven by mechanical stimulation was applied. Solving these two phenomena in the same time frame, the bone regeneration process in the bone-scaffold system was predicted by computational simulation using a voxel finite element method. The change in the mechanical function of the bone-scaffold system during the regeneration process was quantitatively evaluated by measuring the change in total strain energy, and this was used for the evaluation function to optimize the scaffold microstructure that provides the desired mechanical function during and after the bone regeneration process. A case study conducted for the scaffold with a simple microstructure demonstrated that the proposed simulation method could be applied to the design of a porous scaffold microstructure. In addition, the regeneration process was found to be very complex even though the simple rate equations for scaffold regeneration and new bone formation were used because of the coupling effects of these phenomena.

Animals↗
PubMed2005

Combined use of designed scaffolds and adenoviral gene therapy for skeletal tissue engineering.

While tissue engineering remains the most researched alternative to conventional therapies for repair and regeneration, how to optimally combine two of the most promising techniques, designed solid scaffolds and localized gene therapy, is largely unknown. We have conducted a systematic screening of several variables that may affect generation of bone via adenoviral gene therapy vector delivery, on image-based designed and solid freeform-fabricated scaffolds. These variables included: gene therapy type (ex vivo or in vivo); scaffold base material (sintered hydroxyapatite or a polypropylene fumarate/ tricalcium phosphate (PPF/TCP) composite), secondary carrier used to attach the biofactor to the scaffold (fibrin gel or a poly-lactic acid sponge), and scaffold pores size (300 or 800 microm). The in vivo formation of bone following implantation of these scaffolds was then analyzed. Gene therapy method had the largest effect, with ex vivo gene therapy yielding significant amounts of bone on nearly all the implants and in vivo gene therapy failing to produce any bone on most implants. Secondary carrier was the next most important variable, with fibrin gel consistently producing bone encompassing the implants and producing 2-4 times as much bone as the polymer sponge, which triggered only isolated bone growth. Though both scaffold base materials allowed bone growth, hydoxyapatite scaffolds generated twice as much bone as PPF/TCP scaffolds. The pore sizes tested had no significant effect on tissue generation.

Adenoviridae↗
PubMed2005

Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering.

Polycaprolactone (PCL) is a bioresorbable polymer with potential applications for bone and cartilage repair. In this work, porous PCL scaffolds were computationally designed and then fabricated via selective laser sintering (SLS), a rapid prototyping technique. The microstructure and mechanical properties of the fabricated scaffolds were assessed and compared to the designed porous architectures and computationally predicted properties. Scaffolds were then seeded with bone morphogenetic protein-7 (BMP-7) transduced fibroblasts and implanted subcutaneously to evaluate biological properties and to demonstrate tissue in-growth. The work done illustrates the ability to design and fabricate PCL scaffolds with porous architecture that have sufficient mechanical properties for bone tissue engineering applications using SLS. Compressive modulus and yield strength values ranged from 52 to 67 MPa and 2.0 to 3.2 Mpa, respectively, lying within the lower range of properties reported for human trabecular bone. Finite element analysis (FEA) results showed that mechanical properties of scaffold designs and of fabricated scaffolds can be computationally predicted. Histological evaluation and micro-computed tomography (microCT) analysis of implanted scaffolds showed that bone can be generated in vivo. Finally, to demonstrate the clinical application of this technology, we designed and fabricated a prototype mandibular condyle scaffold based on an actual pig condyle. The integration of scaffold computational design and free-form fabrication techniques presented here could prove highly useful for the construction of scaffolds that have anatomy specific exterior architecture derived from patient CT or MRI data and an interior porous architecture derived from computational design optimization.

Animals↗
PubMed2005

Porous scaffold design for tissue engineering.

A paradigm shift is taking place in medicine from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous material scaffolds integrated with biological cells or molecules to regenerate tissues. This new paradigm requires scaffolds that balance temporary mechanical function with mass transport to aid biological delivery and tissue regeneration. Little is known quantitatively about this balance as early scaffolds were not fabricated with precise porous architecture. Recent advances in both computational topology design (CTD) and solid free-form fabrication (SFF) have made it possible to create scaffolds with controlled architecture. This paper reviews the integration of CTD with SFF to build designer tissue-engineering scaffolds. It also details the mechanical properties and tissue regeneration achieved using designer scaffolds. Finally, future directions are suggested for using designer scaffolds with in vivo experimentation to optimize tissue-engineering treatments, and coupling designer scaffolds with cell printing to create designer material/biofactor hybrids.

Animals↗
PubMed2004

Interbody fusion cage design using integrated global layout and local microstructure topology optimization.

STUDY DESIGN: An approach combining global layout and local microstructure topology optimization was used to create a new interbody fusion cage design that concurrently enhanced stability, biofactor delivery, and mechanical tissue stimulation for improved arthrodesis. OBJECTIVE: To develop a new interbody fusion cage design by topology optimization with porous internal architecture. To compare the performance of this new design to conventional threaded cage designs regarding early stability and long-term stress shielding effects on ingrown bone. SUMMARY OF BACKGROUND DATA: Conventional interbody cage designs mainly fall into categories of cylindrical or rectangular shell shapes. The designs contribute to rigid stability and maintain disc height for successful arthrodesis but may also suffer mechanically mediated failures of dislocation or subsidence, as well as the possibility of bone resorption. The new optimization approach created a cage having designed microstructure that achieved desired mechanical performance while providing interconnected channels for biofactor delivery. METHODS: The topology optimization algorithm determines the material layout under desirable volume fraction (50%) and displacement constraints favorable to bone formation. A local microstructural topology optimization method was used to generate periodic microstructures for porous isotropic materials. Final topology was generated by the integration of the two-scaled structures according to segmented regions and the corresponding material density. Image-base finite element analysis was used to compare the mechanical performance of the topology-optimized cage and conventional threaded cage. RESULTS: The final design can be fabricated by a variety of Solid Free-Form systems directly from the image output. The new design exhibited a narrower, more uniform displacement range than the threaded cage design and lower stress at the cage-vertebra interface, suggesting a reduced risk of subsidence. Strain energy density analysis also indicated that a higher portion of total strain energy density was transferred into the new bone region inside the new designed cage, indicating a reduced risk of stress shielding. CONCLUSION: The new design approach using integrated topology optimization demonstrated comparable or better stability by limited displacement and reduced localized deformation related to the risk of subsidence. Less shielding of newly formed bone was predicted inside the new designed cage. Using the present approach, it is also possible to tailor cage design for specific materials, either titanium or polymer, that can attain the desired balance between stability, reduced stress shielding, and porosity for biofactor delivery.

Algorithms↗
PubMed2004

A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity.

An often-proposed tissue engineering design hypothesis is that the scaffold should provide a biomimetic mechanical environment for initial function and appropriate remodeling of regenerating tissue while concurrently providing sufficient porosity for cell migration and cell/gene delivery. To provide a systematic study of this hypothesis, the ability to precisely design and manufacture biomaterial scaffolds is needed. Traditional methods for scaffold design and fabrication cannot provide the control over scaffold architecture design to achieve specified properties within fixed limits on porosity. The purpose of this paper was to develop a general design optimization scheme for 3D internal scaffold architecture to match desired elastic properties and porosity simultaneously, by introducing the homogenization-based topology optimization algorithm (also known as general layout optimization). With an initial target for bone tissue engineering, we demonstrate that the method can produce highly porous structures that match human trabecular bone anisotropic stiffness using accepted biomaterials. In addition, we show that anisotropic bone stiffness may be matched with scaffolds of widely different porosity. Finally, we also demonstrate that prototypes of the designed structures can be fabricated using solid free-form fabrication (SFF) techniques.

Animals↗
PubMed2004

Delivery and protection of adenoviruses using biocompatible hydrogels for localized gene therapy.

Localized gene delivery for repair of bone defects requires appropriate carriers for the gene therapy vectors. The objective of this study was to determine if hydrogels can control temporal and spatial delivery of adenovirus for localized gene therapy. Adenovirus expressing beta-galactosidase was suspended in liquid or fibrin or collagen gels of varied concentrations and incubated prior to testing its bioactivity. The bioactivity of the virus was determined by exposing fibroblasts to the medium, the gels, or the elution medium from the gels. Bioactivity of adenovirus suspended in medium or collagen decreased to half-maximal activity after 15 h of incubation. In contrast, virus suspended in fibrin exhibited a threefold extension of bioactivity and did not reach half-maximal activity for 45 h. Bioactivity of adenovirus in hydrogels was determined to be a function of the gel concentration. In vivo experiments involved intramuscular implantation of BMP-7-expressing adenovirus in collagen, fibrin, or liquid in nude mice for 1, 2, or 4 weeks. Bone formation was observed only after 4 weeks, with bone formation occurring in 80% of muscles implanted with fibrin or collagen and 50% of muscles implanted with liquid. Fibrin gel also led to significantly larger ossicles, indicating that fibrin may offer protection from loss of infectivity both in vivo and in vitro. These results demonstrated that hydrogels may be used as carriers to control delivery of the virus and resultant tissue regeneration.

Adenoviridae↗
PubMed2004

Osteocyte lacuna size and shape in women with and without osteoporotic fracture.

Osteocytes have been hypothesized to control the amount and location of bone tissue which is resorbed or formed, based on the strain magnitude they perceive, and therefore may play a role in the bone loss of osteoporosis. The shape of osteocyte lacunae influences the mechanical strain applied to the osteocyte; thus, it is important to quantify their shape to further understand the mechanical environment of this cell. Previous studies of the size and shape of lacunae have been contradictory and limited to two-dimensional measurements on iliac crest biopsies. This investigation measured the size and shape of osteocyte lacunae in trabecular bone near a typical fracture site from three-dimensional image sets obtained by confocal microscopy. Bone tissue specimens were obtained from individuals undergoing hip replacement subsequent to fracture, and matched cadaveric specimens without fracture. After extensive image processing to differentiate the lacunae from the matrix, the volume and anisotropy of the lacuna were determined. No significant difference was found in the size (volume) or shape (anisotropy) of the lacunae between women with and without osteoporotic fracture, although there was a large range of sizes and shapes in both groups. These results suggest that the size or shape of the lacunae, which influences the strain in osteocytes, does not play a role in osteoporotic fracture. In addition, this study provides geometric measures of lacunae that are important in computational modeling of the mechanical environment of osteocytes.

Aged↗
PubMed2002

Mechanical and in vivo performance of hydroxyapatite implants with controlled architectures.

Internal architecture has a direct impact on the mechanical and biological behaviors of porous hydroxyapatite (HA) implant. However, traditional processing methods provide minimal control in this regard. To address the issue, we developed a new processing method combining image-based design and solid free-form fabrication. We have previously published the processing method showing fabricated HA implants and their chemical properties. This study characterized the mechanical and the in vivo performance of designed HA implants. Thirteen HA implants with orthogonal channels at 40% porosity were tested on an Instron machine. The compressive strength and compressive modulus measured were 30+/-8 MPa and 1.4+/-0.4 GPa, comparable to coralline porous HA. Twenty-four cylindrical HA implants with two architecture designs, orthogonal and radial channels, were implanted in the mandibles of four Yucatan minipigs for 5 and 9 weeks. Normal bone regeneration occurred in both groups. At 9 weeks, bone penetrated 1.4mm into both scaffold designs. The percent bone ingrowth in the penetration zone was higher in the orthogonal channel design but not statistically different due to the low number of samples. However, the overall shape of the regenerated bone tissue was significantly different. In the orthogonal design, bone and HA formed an interpenetrating matrix, while in the radial design, the regenerated bone formed an intact piece at the center of the implant. These preliminary results showed that controlling the overall geometry of the regenerated bone tissue is possible through the internal architectural design of the scaffolds.

Animals↗
PubMedDate not supplied

Engineered osteochondral grafts using biphasic composite solid free-form fabricated scaffolds.

Tissue engineering has provided an alternative to traditional strategies to repair cartilage damaged by injury or degenerative disease. A successful strategy to engineer osteochondral tissue will mimic the natural contour of the articulating surface, achieve native mechanical properties and functional load-bearing ability, and lead to integration with host cartilage and underlying subchondral bone. Image-based design (IBD) and solid free-form (SFF) fabrication can be used to generate scaffolds that are load bearing and match articular geometry. The objective of this study was to utilize materials and biological factors in an integrated approach to regenerate a multitissue interface. Biphasic composite scaffolds manufactured by IBD and SFF fabrication were used to simultaneously generate bone and cartilage in discrete regions and provide for the development of a stable interface between cartilage and subchondral bone. Poly-L-lactic acid/hydroxyapatite composite scaffolds were differentially seeded with fibroblasts transduced with an adenovirus expressing bone morphogenetic protein 7 (BMP-7) in the ceramic phase and fully differentiated chondrocytes in the polymeric phase. After subcutaneous implantation into mice, the biphasic scaffolds promoted the simultaneous growth of bone, cartilage, and a mineralized interface tissue. Within the ceramic phase, the pockets of tissue generated included blood vessels, marrow stroma, and adipose tissue. This combination of IBD and SFF-fabricated biphasic scaffolds with gene and cell therapy is a promising approach to regenerate osteochondral defects.

Animals↗
PubMedDate not supplied

Functional bone engineering using ex vivo gene therapy and topology-optimized, biodegradable polymer composite scaffolds.

Bone tissue engineering could provide an alternative to conventional treatments for fracture nonunion, spinal fusion, joint replacement, and pathological loss of bone. However, this approach will require a biocompatible matrix to allow progenitor cell delivery and support tissue invasion. The construct must also support physiological loads as it degrades to allow the regenerated tissue to bear an increasing load. To meet these complex requirements, we have employed topology-optimized design and solid free-form fabrication to manufacture biodegradable poly(propylene fumarate)/beta-tricalcium phosphate composites. These scaffolds were seeded with primary human fibroblasts transduced with an adenovirus expressing bone morphogenetic protein-7 and implanted subcutaneously in mice. Specimens were evaluated by microcomputed tomography, compressive testing, and histological staining. New bone was localized on the scaffold surface and closely followed its designed contours. Furthermore, the total stiffness of the constructs was retained for up to 12 weeks after implantation, as scaffold degradation and tissue invasion took place.

Adenoviridae↗