Osteoimmune-modulating and BMP-2-eluting anodised 3D printed titanium for accelerated bone regeneration.

3D printing of titanium (Ti) metal has potential to transform the field of personalised orthopaedics and dental implants. However, the impacts of controlled surface topographical features of 3D printed Ti implants on their interactions with the cellular microenvironment and incorporation of biological growth factors, which are critical in guiding the integration of implants with bone, are not well studied. In the present study, we explore the role of surface topological features of 3D printed Ti implants using an anodised titania nanotube (TiNT) surface layer in guiding their immune cell interaction and ability to deliver bioactive form of growth factors. TiNT layers with precisely controlled pore diameter (between 21and 130 nm) were anodically grown on 3D printed Ti surfaces to impart a nano-micro rough topology. Immune biomarker profiles at gene and protein levels show that anodised 3D Ti surfaces with smaller pores resulted in classical activation of macrophages (M1-like), while larger pores (i.e., >100 nm) promoted alternate activation of macrophages (M2-like). The in vitro bone mineralisation studies using the conditioned media from the immunomodulatory studies elucidate a clear impact of pore diameter on bone mineralisation. The tubular structure of TiNTs was utilised as a container to incorporate recombinant human bone morphogenetic protein-2 (BMP-2) in the presence of various sugar and polymeric cryoprotectants. Sucrose offered the most sustainable release of preserved BMP-2 from TiNTs. Downstream effects of released BMP-2 on macrophages as well as bone mineralisation were assessed showing bioactivity retention of the released rhBMP-2. Overall, the TiNT surface topography in combination with controlled, sustained, and local release of bioactive growth factors can potentially enhance the osseointegration outcomes of custom 3D printed Ti implants in the clinic.

Total contact cast for neuropathic diabetic foot ulcers.

OBJECTIVE: To determine the outcome of diabetic neuropathic foot ulcers treated with Total Contact Cast (TCC) in terms of percentage of ulcers healed and time to heal. STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Department of Orthopaedic Surgery, Abbasi Shaheed Hospital, Karachi Medical and Dental College, from April 2005 to March 2007. METHODOLOGY: The study included diabetic patients with non-ischemic neuropathic foot ulcers of upto grade 2 of Wagner's classification. Ulcers were debrided off necrotic tissues and Total Contact Cast (TCC) was applied. TCC was renewed every 2 weeks till healing. Cases were labeled as cast failure when there was no reduction in wound size in 4 consecutive weeks or worsening to a higher grade. Main outcome measures were the percentage of ulcers healed and time to heal in the cast. RESULTS: Thirty four (87.17%) patients were males and 5(12.82%) were females. The mean age was 62 +/- 13.05 years. All patients had NIDDM. Out of the 52 ulcers, 41(78.84%) healed with TCC in an average 2 casts duration (mean 32 days). There were 11(21.15%) cast failure. Majority (63.63%) of cast failure ulcers were located on pressure bearing area of heel. Most (90%) of the ulcers on forefoot and midsole region healed with TCC (p < 0.001). Longer ulcer duration (mean 57.45 +/- 29.64 days) significantly reduced ulcer healing (p < 0.001). CONCLUSION: Total contact cast was an effective treatment modality for neuropathic diabetic foot ulcers of Wagner's grade 2, located on forefoot and midsole region.