Research

Growth of and heterogeneity of conditions pose unique challenges for restoring function. Compounding these challenges are changes in tissue properties during early childhood development that are largely unknown. My research interests focus on uncovering changes in tissue structure function relationships during growth, developing predictive computational models for device testing, designing materials accommodating ease of delivery and directing growth, and scalable manufacture addressing heterogeneity.

Patient specific models of growth and pathology

The changes in tissue structure, function, and mechanics during growth are difficult to study due to the lack of suitable human or animal models. Additionally, the variability in anatomical structures and the heterogeneity of pathologies require patient-specific devices. However, designing these devices is challenging because of the vast number of potential design variations, underscoring the need for high-throughput, low-cost screening approaches. For rare pathologies or those with limited patient populations, computational models can simulate changes in tissue properties and allow for virtual testing of devices. These models can also be used to 3D print anatomical phantoms, which are valuable for bench testing devices, surgical planning, or patient education.

  1. Ramaraju H, Landry AM, Sashidharan S, Shetty A, Crotts SJ, Maher KO, Goudy SL, Hollister SJ Clinical grade manufacture of 3D printed patient specific biodegradable devices for pediatric airway support  Biomaterials. August 2022. [Link]
  2. Ramaraju H, Pithadia K, Crotts SJ, Flanagan CL, Green GE, Hollister SJ, Evaluating Directional Dependency of Selective Laser Sintered Patient Specific Biodegradable Devices to Improve Predictive Modeling and Design Verification. Ann Biomed Eng 49,  2021 [Link]
  3. Ramaraju H, Sferra S, Kunisaki SM, Hollister SJ. Finite element analysis of esophageal atresia repair with biodegradable polymer sleeves. J. Mech Beh. of Biomed. Mat.,Volume 133, September 2022 ,105349 [Link]
Additional Publications >>
  1. Ramaraju H*, Hollister SJ Evaluating nonlinear elasticity and anisotropy of Porcine Diaphragm Central Tendon with Aging. Biomechanics (2024). *PI In Revision
  2. Ramaraju H, Clifton M, Hollister SJ, Predictive modeling and in vivo verification of a full thickness surgical diaphragmatic defect repair. (2024) Under Review
  3. Ramaraju H, Verga AS, Park J, Steedley B, Kowblansky A, Kulagin V, Green GE, Hollister SJ, Predicting growth and degradation of polycaprolactone devices in a 2-year procine model. (2024) Under Review
  4. Ramaraju H*, Akman RE, Hollister SJ. Adressing the impact of multi-modal 3D printing of shape memory polymers on the degradation mechanics suited for articular cartilage. Biofabrication. (2024) *PI In preparation
  5. Ramaraju H*,Benetti S, Hollister SJ, Multimodal evaluation of articular cartilage mechanics reveals microstructural optimization of material mimics using 3D printed lattice structures. Journal of Mehcanical Behavior of Biomedical Materials (2024) *PI In Preparation
  6. Hollister SJ, Crotts SJ, Ramaraju H, Flanagan CL, Zopf DA, Morrison RJ, Les A, Ohye RG, Green GE. Quality Control of 3D Printed Resorbable Implants: The 3D Printed Airway Splint Example. In: Ovsianikov A., Yoo J., Mironov V. (eds) 3D Printing and Biofabrication. pp 131-160.[Link]
  7.  Michaels R, Ramaraju H, Crotts SJ, Hollister SJ, Zopf DA. Early preclinical evaluation of a novel, computer aided designed, 3D printed, bioresorbable posterior cricoid scaffold. Int J Pediatr Otorhinolaryngol. 2021 Nov;150:110892. [Link]
  8. Brooks KA, Lai AY, Tucker SJ, Ramaraju H, Verga A, Shashidharan S, Maher KO, Simon DM, Hollister SJ, Landry AM, Goudy SL. External airway splint placement for severe pediatric tracheobronchomalacia. Int J Pediatr Otorhinolaryngol. 2023 Jun;169:111559. [Link]
Patents >>
  1. Kunisaki S, Hollister SJ, Ramaraju H. Structural Esophageal Repair Through Bioresorbable Esophageal Sleeves, PCT/US2022/072445      
  2. Dasi P, Hollister SJ, Verga AS., Bui H., Ramaraju H., Akman R., Joshi S., Harikrishnan SK., 3D printed bioresorbable heart valve

Instructive Shape Memory Materials

Minimally invasive surgeries (MIS), particularly in pediatrics, are favored over open procedures for their smaller incisions, reduced trauma, and better aesthetics. Biodegradable shape memory polymers (SMPs), which recover their original shape when triggered by heat, light, or other stimuli, are gaining attention for tissue engineering.
Incorporating bioinstructive cues into SMPs is essential for applications like cell-based tissue engineering, inflammation control, and infection prevention. This requires careful design to ensure proper conformation and presentation of cues. Combining these functionalization strategies with 3D printing allows precise spatial control of factors guiding cell behavior, offering significant advantages for complex tissue repair.

  1. Ramaraju H, Garcia-Gomez E, Verga AS, McAtee AM, Hollister SJ, Shape memory cycle conditions impact human bone marrow stromal cell binding to RGD- and YIGSR-conjugated poly (glycerol dodecanedioate). Acta Biomaterialia 2024 Sep 15:186:246-259. [Link]
  2. Ramaraju, H, Kohn, DH, “Cell and Material-Specific Phage Display Peptides Increase iPS-MSC Mediated Bone and Vasculature Formation In Vivo” Advanced Healthcare Materials 2019 May;8(9):e1801356. [Link]
  3. Ramaraju, H, Miller, SS, and Kohn, DH, “Dual-functioning peptides discovered by phage display increase the magnitude and specificity of BMSC attachment to mineralized biomaterials.” Biomaterials. 2017 Jul;134:1-12 [Link]
Additional Publications >>
  1. Ramaraju, H, Miller, SS, and Kohn, DH, “Dual-functioning phage derived peptides encourage human bone marrow cell specific attachment to mineralized biomaterials,” In: 11th ICCBMT Proceedings Issue of the journal Connective Tissue Research. Connective Tissue Research. 2014 Aug;55 Suppl 1:160-3[Link]
  2. Ramaswamy J, Nam HK, Ramaraju H, Hatch NE, Kohn DH, “Inhibition of osteoblast mineralization by phosphorylated phage-derived apatite-specific peptide.” Biomaterials. 2015 Dec;73 120-30.[Link]
  3. Ramaraju H, Ul-Haque A, Verga AS, Bocks ML, Hollister SJ, Modulating nonlinear elastic behavior of biodegradable shape memory elastomer and small intestinal submucosa(SIS) composites for soft tissue repair, J. Mech Beh. of Biomed. Mat.,Volume 110, 2020 [Link]
Patents >>

Ramaraju, H and Hollister SJ. Bioresorbable Implant Materials and Methods of Making the Same US 18/287,475

Responsive Shape Memory Materials

Responsive shape memory biomaterials can be designed to enable a dynamic and personalized approach to regeneration. Tissue growth and remodeling often occur in non-linear, unpredictable patterns, limiting device performance throughout the repair process. SMPs address this by responding to external triggers—such as heat, light, magnetic fields, or ultrasound—to modulate their behavior in real-time. This capability facilitates on-demand control over mechanical properties or the timed release of growth factors, bioactive molecules, or other instructive cues.

  1. Ramaraju H, Masarella D, Wong C, Verga AS, Kish E, Bocks ML, Hollister SJ, Percutaneous delivery and degradation of a shape memory elastomer poly(glycerol dodecanedioate) in porcine pulmonary arteries. Biomaterials.  2023. [Link]
  2. Akman RE*, Ramaraju H*, Verga A, Hollister SJ. Multimodal 3D printing of biodegradable shape memory elastomer resins for patient specific soft tissue repair. Applied Materials Today. Volume 29 December 2022, 101666[Link]
  3. Ramaraju H., Akman RE, Safranski DL, Hollister SJ, Designing Biodegradable Shape Memory Polymers for Tissue Repair. Adv. Func. Mat. 2020, 30, 2002014. [Link]
Additional Publications >>
  1. WangL, JinK, LiN, XuP, YuanH, Ramaraju H, Hollister SJ, Fan Y., Innovative design of minimal invasive biodegradable poly(glycerol-dodecanoate) nucleus pulposus scaffold with function regeneration. Nat. Comm. 2023. [Link]
  2. Jin K, Wang L, Zhang K, Ramaraju H, Hollister SJ, Fan Y. Biodegradation Behavior Control for Shape Memory Polyester Poly(Glycerol Dodecanedioate): An In Vivo and In Vitro Study. Biomacromolecules. 2023. [Link]
  3. Akman R.*, Ramaraju H.* and Hollister S.J. (2021), Development of Photocrosslinked Poly(glycerol dodecanedioate)—A Biodegradable Shape Memory Polymer for 3D-Printed Tissue Engineering Applications. Adv. Eng. Mater., 23: 2100219. [Link]
  4. Ramaraju H, McAtee AM, Akman RE, Verga AS, Bocks ML, Hollister SJ, Sterilization Effects on Poly Glycerol Dodecanedioate(PGD), a Biodegradable Shape Memory Elastomer. Journal of Biomedical Materials Research 2022;1‐13.[Link]
  5. Ramaraju H, Solorio LD, Bocks ML, Hollister SJ (2020) Degradation properties of a biodegradable shape memory elastomer, poly(glycerol dodecanoate), for soft tissue repair. PLoS ONE 15(2): e0229112. [Link]
  6. Omer A, Tiruchinapally G, Youssef I, Ramaraju H, Durmaz YY, Kozloff K, Kohn DH, and ElSayed M. 2022. “Selective Binding of pVTK Peptide- and Bisphosphonate-Functionalized Micelles to Prostate Cancer Cells, Osteoblasts, and Osteoclasts.” Precision Nanomedicine 5 (1): 851–69. [Link]
Patents >>

Ramaraju H, Hollister SJ., Akman RE. Photocurable Materials for Additive Manufacturing of Biomedical Devices, PCT 63/208,259