3D Printing in alloy design to improve biocompatibility in metallic implants.

3D Printing (3DP) or additive manufacturing (AM) enables parts with complex shapes, design flexibility, and customization opportunities for defect specific patient-matched implants. 3DP or AM also offers a design platform that can be used to innovate novel alloys for application-specific compositional modifications. In medical applications, the biological response from a host tissue depends on a biomaterial's structural and compositional properties in the physiological environment. Application of 3DP can pave the way towards manufacturing innovative metallic implants, combining structural variations at different length scales and tailored compositions designed for specific biological responses. This study shows how 3DP can be used to design metallic alloys for orthopedic and dental applications with improved biocompatibility using in vitro and in vivo studies. Titanium (Ti) and its alloys are used extensively in biomedical devices due to excellent fatigue and corrosion resistance and good strength to weight ratio. However, Ti alloys' in vivo biological response is poor due to its bioinert surface. Different coatings and surface modification techniques are currently being used to improve the biocompatibility of Ti implants. We focused our efforts on improving Ti's biocompatibility via a combination of tantalum (Ta) chemistry in Ti, the addition of designed micro-porosity, and nanoscale surface modification to enhance both in vitro cytocompatibility and early stage in vivo osseointegration, which was studied in rat and rabbit distal femur models.

Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.

Use of single-agent carboplatin as adjuvant or neoadjuvant therapy in conjunction with amputation for appendicular osteosarcoma in dogs.

Survival following amputation and administration of single-agent carboplatin for treatment of appendicular osteosarcoma (OSA) in dogs was retrospectively examined. Records of 155 dogs with appendicular OSA treated with amputation and single-agent carboplatin were included from 14 centers. Any carboplatin dosage, number of doses, and protocol schedule were eligible for inclusion. The median disease-free interval (DFI) was 256 days. The median overall survival time was 307 days. Similar prognostic survival factors were identified in this study as reported in prior studies of canine appendicular OSA. Median DFI and survival were comparable to those reported in the original Bergman et al publication. Carboplatin treatment improves the survival probability in dogs with appendicular OSA compared to amputation alone and remains an acceptable alternative to adjuvant treatment with cisplatin.

Additively manufactured calcium phosphate reinforced CoCrMo alloy: Bio-tribological and biocompatibility evaluation for load-bearing implants.

Cobalt-chromium-molybdenum (CoCrMo) alloys are widely used in load-bearing implants; specifically, in hip, knee, and spinal applications due to their excellent wear resistance. However, due to in vivo corrosion and mechanically assisted corrosion, metal ion release occurs and accounts for poor biocompatibility. Therefore, a significant interest to find an alternative to CoCrMo alloy exists. In the present work we hypothesize that calcium phosphate (CaP) will behave as a solid lubricant in CoCrMo alloy under tribological testing, thereby minimizing wear and metal ion release concerns associated with CoCrMo alloy. CoCrMo-CaP composite coatings were processed using laser engineered net shaping (LENS™) system. After LENS™ processing, CoCrMo alloy was subjected to laser surface melting (LSM) using the same LENS™ set-up. Samples were investigated for microstructural features, phase identification, and biocompatibility. It was found that LSM treated CoCrMo improved wear resistance by 5 times. CoCrMo-CaP composites displayed the formation of a phosphorus-based tribofilm. In vitro cell-material interactions study showed no cytotoxic effect. Sprague-Dawley rat and rabbit in vivo study displayed increased osteoid formation for CoCrMo-CaP composites, up to 2 wt.% CaP. Our results show that careful surface modification treatments can simultaneously improve wear resistance and in vivo biocompatibility of CoCrMo alloy, which can correlate to a reduction of metal ion release in vivo.

Use of alternating administration of carboplatin and doxorubicin in dogs with microscopic metastases after amputation for appendicular osteosarcoma: 50 cases (1999-2006).

OBJECTIVE: To evaluate the efficacy and toxicity of an alternating carboplatin and doxorubicin chemotherapy protocol in dogs with putative microscopic metastases after amputation for appendicular osteosarcoma and assess patient-, tumor-, and treatment-related factors for associations with prognosis. DESIGN: Retrospective case series. ANIMALS: 50 client-owned dogs. PROCEDURES: Records of dogs that underwent amputation for appendicular osteosarcoma and received an alternating carboplatin and doxorubicin chemotherapy protocol were reviewed. Dogs had full staging and were free of detectable metastases prior to chemotherapy. Data on disease-free interval (DFI), survival time, and toxicoses were retrieved from medical records and owner or referring veterinarian communications. RESULTS: Median DFI was 202 days. Median survival time was 258 days. Twenty-nine (58%) dogs completed the protocol as planned, and the rest were withdrawn typically because of metastases or toxicoses. Grade 3 or 4 myelosuppression was reported in 9 of 50 (18%) dogs and grade 3 or 4 gastrointestinal toxicosis in 6 of 50 (12%) dogs. There were no chemotherapy-related fatalities. Univariate factors associated with significant improvement in DFI included tumor location (radius), receiving doxorubicin as the first drug, starting chemotherapy more than 14 days after amputation, and no rib lesions on preamputation bone scans. Multivariate factors associated with a significant improvement in survival time were tumor location (radius) and completing chemotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Alternating administration of carboplatin and doxorubicin resulted in DFI and survival time similar to those reported for single-agent protocols. Clients should be counseled regarding the likelihood of toxicoses. Relevance of sequence and timing of starting chemotherapy should be further evaluated.

Reconstruction of chest wall defects after rib tumor resection: a comparison of autogenous, prosthetic, and composite techniques in 44 dogs.

OBJECTIVE: To compare short- and long-term outcome and complications of chest wall reconstruction in dogs using autogenous, prosthetic, and composite autogenous-prosthetic techniques. STUDY DESIGN: Historical cohort. ANIMALS: Dogs (n=44) with spontaneous tumors arising from or involving the chest wall. METHODS: Medical records were reviewed for dogs with rib and/or sternal tumors treated by chest wall resection and reconstruction. Signalment, preoperative clinical features, intraoperative findings and complications, reconstruction technique (autogenous muscle flap, prosthetic mesh, or composite autogenous-prosthetic technique), and short- (< or =14 days) and long-term (>14 days) postoperative complications were determined from the medical records and telephone contact with owners and referring veterinarians. Associations between chest wall reconstruction technique and postoperative complications were tested with Cox proportional hazards. RESULTS: Chest wall defects were reconstructed with autogenous muscle flaps (29 dogs), prosthetic mesh (3), and a composite technique of prosthetic mesh and either autogenous muscle or omental pedicle flap (12). Early postoperative complications were recorded in 8 dogs (18.2%) and included seroma (5) and pleural effusion and peripheral edema (3). One dog had a late complication (2.3%) with a mesh-related infection 767 days postoperatively. Overall, complications occurred in 10.3% of autogenous, 25.0% of composite, and 66.7% of prosthetic reconstructions. Chest wall reconstruction with Marlex mesh alone was associated with a significantly increased risk of postoperative complications compared with autogenous reconstruction (P=.027). Reconstruction of sternal defects (3), 2 of which were performed with Marlex mesh alone, was associated with a significantly increased risk of complications compared with lateral chest wall reconstructions (P=.037). CONCLUSIONS: Large chest wall defects can be reconstructed with autogenous and composite techniques, but prosthetic mesh should be covered with well-vascularized autogenous muscle or omentum to decrease the risk of postoperative complications. Sternal defects should be reconstructed with rigid techniques. CLINICAL RELEVANCE: Chest wall reconstruction with autogenous muscle flaps or a combination of autogenous techniques with prosthetic mesh is associated with a low rate of infection and other complications.

Oncologic outcome after curative-intent treatment in 39 dogs with primary chest wall tumors (1992-2005).

OBJECTIVE: To describe the clinical features and determine oncologic outcome and prognostic factors for dogs with primary tumors of the osseous chest wall. STUDY DESIGN: Historical cohort. ANIMALS: Dogs (n=39) with spontaneous tumors involving the chest wall. METHODS: Medical records were reviewed for dogs with rib and/or sternal tumors treated by chest wall resection and reconstruction. Signalment, preoperative clinical features, reconstruction technique, and oncologic outcome (local tumor recurrence, metastasis, and survival time) were determined from medical records and by telephone contact with owners and referring veterinarians. Oncologic outcome and prognostic factors were determined using Kaplan-Meier survival analysis and Cox proportional hazards. Logistic regression was used to determine if increased serum alkaline phosphatase (ALP) concentration was associated with tumor type. RESULTS: Of the 39 dogs with tumors arising from the chest wall, 25 had osteosarcoma, 12 had chondrosarcoma, and 2 dogs had hemangiosarcoma. Median survival time (MST) for dogs with rib osteosarcoma was 290 days. Increased activity of total ALP significantly decreased survival in dogs with osteosarcoma (210 days versus 675 days, P=.0035). MST for dogs with rib chondrosarcoma was not reached (mean 1301 days) and survival was significantly greater than all other types of rib tumors (P=.0321). CONCLUSION: Rib tumors should be resected with wide margins to decrease the risk of incomplete excision, because local tumor recurrence has a significant impact on the survival time. The prognosis for dogs with rib chondrosarcoma is very good, but guarded for other types of tumors. CLINICAL RELEVANCE: Osteosarcoma and chondrosarcoma are the most common primary tumors of the chest wall. Prognosis for dogs with primary rib chondrosarcoma is very good with surgery alone, but surgery and adjunctive chemotherapy is recommended for dogs with primary rib osteosarcoma and the prognosis remains guarded.

Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study.

BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.

Evaluation of primary re-excision after recent inadequate resection of soft tissue sarcomas in dogs: 41 cases (1999-2004).

OBJECTIVE: To determine the efficacy of primary re-excision alone for treatment of soft tissue sarcomas after recent incomplete resection, the frequency and clinical importance of detecting residual tumor in resected scars, and prognostic factors associated with the procedure. DESIGN: Retrospective case series. ANIMALS: 41 dogs. PROCEDURES: Medical records of dogs that had undergone recent incomplete excision of a soft tissue sarcoma at a referring veterinary practice and subsequent re-excision of the scar at the Colorado State University Veterinary Medical Center were reviewed. Owners and referring veterinarians were contacted for follow-up information. Slides from re-excised specimens were reviewed. Dogs that underwent radiation therapy after the re-excision procedure were excluded. RESULTS: 41 dogs met the inclusion criteria, and long-term follow-up information was available for 39 dogs. Median follow-up time was 816 days. Local recurrence of tumor developed in 6 of 39 (15%) dogs, and distant metastasis occurred in 4 of 39 (10%) dogs. Healthy tissue margins of 0.5 to 3.5 cm were achieved at re-excision. Residual tumor was identified in 9 of 41 (22%) resected scars. No tumor-, patient-, or treatment-related variables were associated with local recurrence except for the presence of liposarcoma or fibrosarcoma or whether fine-needle aspiration had been performed prior to surgery. CONCLUSIONS AND CLINICAL RELEVANCE: After incomplete resection of soft tissue sarcomas, resection of local tissue should be performed, even if excisable tissue margins appear narrow. A long-term favorable prognosis is achievable without radiation therapy or amputation. The presence of residual tumor in resected scar tissue should not be used to predict local recurrence.

Effects of MgO and SiO2 on Plasma-Sprayed Hydroxyapatite Coating: An in Vivo Study in Rat Distal Femoral Defects.

Plasma-sprayed hydroxyapatite (HA)-coated titanium implants have been widely used in orthopedic applications due to their inheritance of an excellent mechanical property from titanium and great osteoconductivity from HA. However, the lack of osteoinductivity limits their further applications. In this study, 1 wt % MgO and 0.5 wt % SiO2 were mixed with HA for making plasma-sprayed coatings on titanium implants. Plasma-sprayed HA- and MgO/SiO2-HA-coated titanium implants showed adhesive bond strengths of 25.73 ± 1.92 and 23.44 ± 2.89 MPa, respectively. The presence of MgO and SiO2 significantly increased the osteogenesis, osseointegration, and bone mineralization of HA-coated titanium implants by the evaluation of their histomorphology after 6, 10, and 14 weeks of implantation in rat distal femoral defects. Implant pushout tests also showed a shear modulus of 149.83 ± 3.69 MPa for MgO/SiO2-HA-coated implants after 14 weeks of implantation, compared to 52.68 ± 10.41 MPa for uncoated implants and 83.92 ± 3.68 MPa for pure HA-coated implants; These are differences in the shear modulus of 96% and 56.4%, respectively. This study assesses for the first time the quality of the bone-implant interface of induction plasma-sprayed MgO and SiO2 binary-doped HA coatings on load-bearing implants compared to bare titanium and pure HA coatings in a quantitative manner. Relating the osseointegration and interface shear modulus to the quality of implant fixation is critical to the advancement and implementation of HA-coated orthopedic implants.

Evaluation of survival time in dogs with stage III osteosarcoma that undergo treatment: 90 cases (1985-2004).

OBJECTIVE-To assess survival time in dogs that underwent treatment for stage III osteosarcoma and evaluate factors affecting survival. DESIGN-Retrospective case series. ANIMALS-90 dogs with stage III osteosarcoma. PROCEDURES-Records in the osteosarcoma database at the Animal Cancer Center at Colorado State University from 1985 to 2004 were searched for dogs with metastatic disease at the time of evaluation. Dogs were included in the study if they had metastasis to any site and if treatment was initiated. A Kaplan-Meier survival analysis was performed, and the influences of age, sex, breed, primary tumor site, metastatic sites, and treatment on outcome were analyzed via log-rank analysis. RESULTS-Median survival time was 76 days, with a range of 0 to 1,583 days. No significant differences in survival times on the basis of age, sex, breed, or primary site were observed. Breeds and primary tumor sites were typical of those usually associated with osteosarcoma in dogs. Dogs treated palliatively with radiation therapy and chemotherapy had a significantly longer survival time (130 days) than dogs in all other treatment groups. Dogs treated with surgery alone had a significantly shorter survival time (3 days) than dogs treated with surgery and chemotherapy (78 days). Dogs with bone metastases had a longer survival time than dogs with soft tissue metastases. CONCLUSIONS AND CLINICAL RELEVANCE-Treatment of dogs with stage III osteosarcoma can result in various survival times. Dogs with metastasis to bone and dogs that were treated palliatively with radiation and chemotherapy had the longest survival times.

Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998-2004).

OBJECTIVE: To evaluate prognostic factors associated with outcome of dogs with multiple cutaneous mast cell tumors (MCTs) treated with surgery with or without adjuvant treatment. DESIGN: Retrospective case series. ANIMALS: 54 dogs with a minimum of 2 simultaneous, histologically confirmed cutaneous MCTs that had been excised and had adequate staging and follow-up data. PROCEDURE: Medical records from 1998 to 2004 were examined. Outcome was assessed with the Kaplan-Meier product-limit method and log-rank analysis. Prognostic factors evaluated included signalment; number, histologic grade, location, size, local recurrence, and de novo development of MCTs; quality of surgical margins; clinical signs at the time of diagnosis; and use of adjuvant treatment. RESULTS: Medical records of 54 dogs with 153 tumors were included. Median follow-up time was 658 days. Median disease-free interval (1,917 days; range, 11 to 1,917 days) and median survival time (1,917 days; range, 14 to 1,917 days) were not yet reached. The 1- year and 2- to 5-year survival rates were 87% and 85%, respectively. The overall rate of metastasis was 15%. Factors that negatively influenced survival time in the univariate analysis included incomplete excision, local recurrence, size > 3 cm, clinical signs at the time of diagnosis, and use of adjuvant treatment. Presence of clinical signs at the time of diagnosis was the only negative prognostic factor for disease-free interval detected in the multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that multiple cutaneous MCTs in dogs are associated with a low rate of metastasis and a good prognosis for long-term survival with adequate excision of all MCTs.

Initial wound management.

A wounded patient can be presented to the veterinary surgeon under a number of circumstances. The wound could result from external trauma,such as vehicle trauma or an animal fight, or it could have been created by surgical intervention, such as the removal of a mass. A wound could also be secondary to a failed initial attempt at wound closure. No matter what the cause, initial wound management often follows similar pathways. A successful wound closure and healing outcome is often dependent on adherence to basic principles of wound assessment, appropriate care, and reassessment. This article covers the approach to and specific options for the initial stages of wound management.

Clinical evaluation of mitoxantrone and piroxicam in a canine model of human invasive urinary bladder carcinoma.

PURPOSE: Cyclooxygenase inhibitors show promise in chemoprevention and therapy of certain carcinomas, an effect that may be additive to that of standard chemotherapy. The purpose of this study was to evaluate the efficacy of combined therapy using the cyclooxygenase inhibitor, piroxicam, and mitoxantrone against a relevant canine model of human invasive bladder cancer. EXPERIMENTAL DESIGN: Fifty-five dogs with transitional cell carcinoma of the urinary bladder were enrolled in this nonrandomized one-armed prospective multi-institutional clinical trial. Mitoxantrone was administered i.v. (5 mg/m(2)) every 21 days for four treatments, and piroxicam was administered p.o. (0.3 mg/kg/day) for the study duration. Tumor staging was performed at baseline, day 42 and every 3 months after protocol completion. Endpoints included time-to-treatment failure and survival time (ST). RESULTS: Response data were available for 48 dogs and included one complete response, 16 partial responses, 22 with disease stabilization, and 9 with progressive disease for an overall 35.4% measurable response rate. Subjective improvement occurred in 75% of treated dogs. Median time-to-treatment failure and ST were 194 and 350 days, respectively. Using censoring and end point definitions similar to those of previous reports of dogs treated with piroxicam alone, the median ST in this study was 291 days, compared with 181 days with piroxicam alone. Diarrhea and azotemia were the most common treatment complications. CONCLUSIONS: Mitoxantrone/piroxicam induced remission more frequently than previously reported for either drug as a single agent in this canine model of invasive human transitional cell carcinoma. Additional evaluation of these drugs in combination protocols should be explored.

Incidence and prognostic importance of lymph node metastases in dogs with appendicular osteosarcoma: 228 cases (1986-2003).

OBJECTIVE: To determine the incidence of regional lymph node metastasis in dogs with appendicular osteosarcoma and determine whether regional lymph node metastasis was associated with shortened disease-free interval or survival time. DESIGN: Retrospective study. ANIMALS: 228 dogs with appendicular osteosarcoma in which regional lymph nodes were examined histologically at the time of limb amputation. PROCEDURE: Information collected from the medical records included signalment; affected site; initial serum alkaline phosphatase activity; whether treatment involved adjuvant chemotherapy and, if so, chemotherapeutic agents administered and number of treatments; disease-free interval; and survival time. RESULTS: 10 (4.4%) dogs had histologic evidence of regional lymph node metastasis at the time of amputation. Median disease-free interval for dogs without regional lymph node metastasis (238 days; range, 0 to 1,067 days) was significantly longer than median disease-free interval for dogs with regional lymph node metastasis (48 days; range, 2 to 269 days). Median survival time for dogs without lymph node metastasis (318 days; range, 20 to 1,711 days) was significantly longer than median survival time for dogs with lymph node metastasis (59 days; range, 19 to 365 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that regional lymph node metastasis is rare in dogs with appendicular osteosarcoma but that dogs with lymph node metastasis have a poorer prognosis than do dogs without.

Partial foot amputation in 11 dogs.

Eleven dogs with malignant tumors of the digits and feet were treated with partial foot amputation. Partial foot amputation involved amputation of one or both central weight-bearing digits. Lameness occurred in all dogs but resolved in eight dogs at a median of 37 days postoperatively. In the remaining three dogs, lameness improved but did not resolve. Tumor control was excellent, with no evidence of local recurrence in 10 dogs. One dog underwent limb amputation. Based on these results, partial foot amputation may be recommended in the management of malignant tumors of the canine foot in which more than one digit must be amputated to achieve adequate surgical margins.

SrO- and MgO-doped microwave sintered 3D printed tricalcium phosphate scaffolds: mechanical properties and in vivo osteogenesis in a rabbit model.

The presence of interconnected macro pores allows guided tissue regeneration in tissue engineering scaffolds. However, highly porous scaffolds suffer from having poor mechanical strength. Previously, we showed that microwave sintering could successfully be used to improve mechanical strength of macro porous tricalcium phosphate (TCP) scaffolds. This study reports the presence of SrO and MgO as dopants in TCP scaffolds improves mechanical and in vivo biological performance. We have used direct three dimensional printing (3DP) technology for scaffold fabrication. These 3DP scaffolds possessed multiscale porosity, that is, 3D interconnected designed macro pores along with intrinsic micro pores. A significant increase in mechanical strength, between 37 and 41%, was achieved due to SrO and MgO doping in TCP as compared with pure TCP. Maximum compressive strengths of 9.38 ± 1.86 MPa and 12.01 ± 1.56 MPa were achieved by conventional and microwave sintering, respectively, for SrO-MgO-doped 3DP scaffolds with 500 µm designed pores. Histomorphological and histomorphometric analysis revealed a significantly higher osteoid, bone and haversian canal formation induced by the presence of SrO and MgO dopants in 3DP TCP as compared with pure TCP scaffolds when tested in rabbit femoral condyle defect model. Increased osteon and thus enhanced network of blood vessel formation, and osteocalcin expression were observed in the doped TCP scaffolds. Our results show that these 3DP SrO-MgO-doped TCP scaffolds have the potential for early wound healing through accelerated osteogenesis and vasculogenesis.

Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors.

There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors, and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need.

An initial investigation of photocurable three-dimensional lactic acid based scaffolds in a critical-sized cranial defect.

Degradable polymer networks formed by the photoinitiated polymerization of multifunctional monomers have great potential as in situ forming materials, especially for bone tissue engineering. In this study, one specific chemistry was analyzed with respect to bone formation in a critical-sized defect model with and without adsorbed osteoinductive growth factors present. The scaffolds degraded in approximately 8 months and possessed an elastic modulus similar to that of trabecular bone. A porous scaffold fabricated with approximately 80% porosity and pore diameters ranging from 45 to 150 mm was implanted in a critical-sized cranial defect in rats. When implanted alone, the scaffolds were filled primarily with fibrous tissue after 9 weeks with only mild inflammation at the defect site. When the scaffolds released osteoinductive growth factors, statistically more bone filled the scaffold. For instance, 65.8+/-9.4% (n=5) of the defects were filled with radiopaque tissue in the osteoinductive releasing scaffolds, whereas only 24.2+/-7.4% (n=5) of the defects were filled in the untreated defects 9 weeks after implantation. These results illustrate not only the benefits of delivering osteoinductive factors when developing synthetic bone grafts, but the potential of these materials for supporting the infiltration and development of bone in large defects.