FAK-mediated mechanotransduction in skeletal regeneration

The majority of cells are equipped to detect and decipher physical stimuli, and then react to these stimuli in a cell type-specific manner. Ultimately, these cellular behaviors are synchronized to produce a tissue response, but how this is achieved remains enigmatic. Here, we investigated the genetic basis for mechanotransduction using the bone marrow as a model system. We found that physical stimuli produced a pattern of principal strain that precisely corresponded to the site-specific expression of sox9 and runx2, two transcription factors required for the commitment of stem cells to a skeletogenic lineage, and the arrangement and orientation of newly deposited type I collagen fibrils. To gain insights into the genetic basis for skeletal mechanotransduction we conditionally inactivated focal adhesion kinase (FAK), an intracellular component of the integrin signaling pathway. By doing so we abolished the mechanically induced osteogenic response and thus identified a critical genetic component of the molecular machinery required for mechanotransduction. Our data provide a new framework in which to consider how physical forces and molecular signals are synchronized during the program of skeletal regeneration

Quantitative analysis of bone reactions to relative motions at implant-bone interfaces

Connective soft tissues at the interface between implants and bone, such as in human joint replacements, can endanger the stability of the implant fixation. The potential of an implant to generate interface bone resorption and form soft tissue depends on many variables, including mechanical ones. These mechanical factors can be expressed in terms of relative motions between bone and implant at the interface or deformation of the interfacial material.\ud \ud The purpose of this investigation was to determine if interface debonding and subsequent relative interface motions can be responsible for interface degradation and soft tissue interposition as seen in experiments and clinical results. A finite element computer program was augmented with a mathematical description of interface debonding, dependent on interface stress criteria, and soft tissue interface interposition, dependent on relative interface motions. Three simplified models of orthopaedic implants were constructed: a cortical bone screw for fracture fixation plates, a femoral resurfacing prosthesis and a straight stem model, cemented in a bone. The predicted computer configurations were compared with clinical observations. The computer results showed how interface disruption and fibrous tissue interposition interrelate and possibly enhance each other, whereby a progressive development of the soft tissue layer can occur.\ud \ud Around the cortical bone screw, the predicted resorption patterns were relatively large directly under the screw head and showed a pivot point in the opposite cortex. The resurfacing cup model predicted some fibrous tissue formation under the medial and lateral cup rim, whereby the medial layer developed first because of higher initial interface stresses. The straight stem model predicted initial interface failure at the proximal parts. After proximal resorption and fibrous tissue interposition, the medial interface was completely disrupted and developed an interface layer. The distal and mid lateral side maintained within the strength criterion.\ud \ud Although the applied models were relatively simple, the results showed reasonable qualitative agreement with resorption patterns found in clinical studies concerning bone screws and the resurfacing cup. The hypothesis that interface debonding and subsequent relative (micro)motions could be responsible for bone resorption and fibrous tissue propagation is thereby sustained by the results

Bone healing response in cyclically loaded implants : comparing zero, one, and two loading sessions per day

When bone implants are loaded, they are inevitably subjected to displacement relative to bone. Such micromotion generates stress/strain states at the interface that can cause beneficial or detrimental sequels. The objective of this study is to better understand the mechanobiology of bone healing at the tissue-implant interface during repeated loading. Machined screw shaped Ti implants were placed in rat tibiae in a hole slightly bigger than the implant diameter. Implants were held stable by a specially-designed bone plate that permits controlled loading. Three loading regimens were applied, (a) zero loading, (b) one daily loading session of 60 cycles with an axial force of 1.5 N/cycle for 7 days, and (c) two such daily sessions with the same axial force also for 7 days. Finite element analysis was used to characterize the mechanobiological conditions produced by the loading sessions. After 7 days, the implants with surrounding interfacial tissue were harvested and processed for histological, histomorphometric and DNA microarray analyses. Histomorphometric analyses revealed that the group subjected to repeated loading sessions exhibited a significant decrease in bone-implant contact and increase in bone-implant distance, as compared to unloaded implants and those subjected to only one loading session. Gene expression profiles differed during osseointegration between all groups mainly with respect to inflammatory and unidentified gene categories. The results indicate that increasing the daily cyclic loading of implants induces deleterious changes in the bone healing response, most likely due to the accumulation of tissue damage and associated inflammatory reaction at the bone-implant interface

The effect of thread pattern upon implant osseointegration

Objectives : Implant design features such as macro- and micro-design may influence overall implant success. Limited information is currently available. Therefore, it is the purpose of this paper to examine these factors such as thread pitch, thread geometry, helix angle, thread depth and width as well as implant crestal module may affect implant stability. Search Strategy : A literature search was conducted using MEDLINE to identify studies, from simulated laboratory models, animal, to human, related to this topic using the keywords of implant thread, implant macrodesign, thread pitch, thread geometry, helix angle, thread depth, thread width and implant crestal module. Results : The results showed how thread geometry affects the distribution of stress forces around the implant. A decreased thread pitch may positively influence implant stability. Excess helix angles in spite of a faster insertion may jeopardize the ability of implants to sustain axial load. Deeper threads seem to have an important effect on the stabilization in poorer bone quality situations. The addition of threads or microthreads up to the crestal module of an implant might provide a potential positive contribution on bone-to to-implant contact as well as on the preservation of marginal bone; nonetheless this remains to be determined. Conclusions : Appraising the current literature on this subject and combining existing data to verify the presence of any association between the selected characteristics may be critical in the achievement of overall implant success. To cite this article: Abuhussein H, Pagni G, Rebaudi A, Wang H-L. The effect of thread pattern upon implant osseointegration. Clin. Oral Impl. Res . 21 , 2010; 129–136. doi: 10.1111/j.1600-0501.2009.01800.xPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74748/1/j.1600-0501.2009.01800.x.pd

A Bioengineered Implant for a Predetermined Bone Cellular Response to Loading Forces. A Literature Review and Case Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142048/1/jper1276.pd

Surface Modification of Biomedical and Dental Implants and the Processes of Inflammation, Wound Healing and Bone Formation

Bone adaptation or integration of an implant is characterized by a series of biological reactions that start with bone turnover at the interface (a process of localized necrosis), followed by rapid repair. The wound healing response is guided by a complex activation of macrophages leading to tissue turnover and new osteoblast differentiation on the implant surface. The complex role of implant surface topography and impact on healing response plays a role in biological criteria that can guide the design and development of future tissue-implant surface interfaces

Critical review of immediate implant loading

Background : Implant dentistry has become successful with the discovery of the biological properties of titanium. In the original protocol, studies have advocated a 2-stage surgical protocol for load-free and submerged healing to ensure predictable osseointegration. However, the discomfort, inconvenience, and anxiety associated with waiting period remains a challenge to both patients and clinicians. Hence, loading implant right after placement was attempted and has gained popularity among clinicians. Issues/questions related to this approach remain unanswered. Therefore, it is the purpose of this review article to (1) review and analyze critically the current available literature in the field of immediate implant loading and (2) discuss, based on scientific evidence, factors that may influence this treatment modality. Material and Methods : Literature published over the past 20 years was selected and reviewed. Findings from these studies were discussed and summarized in the tables. The advantages and disadvantages associated with immediate implant loading were analyzed. Factors that may influence the success of immediate implant loading, including patient selection, type of bone quality, required implant length, micro- and macrostructure of the implant, surgical skill, need for achieving primary stability/control of occlusal force, and prosthesis guidelines, were thoroughly reviewed and discussed. Results and Conclusion : Various studies have demonstrated the feasibility and predictability of this technique. However, most of these articles are based on retrospective data or uncontrolled cases. Randomized, prospective, parallel-armed longitudinal human trials are primarily based on short-term results and long-term follow-ups are still scarce in this field. Nonetheless, from available literature, it may be concluded that anatomic locations, implant designs, and restricted prosthetic guidelines are key to ensure successful outcomes. Future studies, preferably randomized, prospective longitudinal studies, are certainly needed before this approach can be widely used. To cite this article: Gapski R, Wang H-L, Mascarenhas P, Lang NP. Critical review of immediate implant loading. Clin. Oral Impl. Res , 14 , 2003; 515–527Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73058/1/j.1600-0501.2003.00950.x.pd