Bone Regenerative Engineering Using a Protein Kinase A-Specific Cyclic AMP Analogue Administered for Short Term

Ifegwu, Okechukwu Clinton; Awale, Guleid; Kan, Ho Man; Rajpura, Komal; O’Neill, Edward; Kuo, Chia‐Ling; Lo, Kevin W.‐H.

doi:10.1007/s40883-018-0063-1

Cited by 18 publications

(11 citation statements)

References 65 publications

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“…Regenerative engineering of this complex tissue via the localized and controlled delivery of clinically‐translatable biological therapeutics sustained through the active healing period post‐surgical repair is a promising approach for improving post‐operative tendon and enthesial fibrocartilage tissue quality. Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology, and Clinical Translation for the regeneration of complex tissues 2‐20 such as the rotator cuff enthesis. Traditionally, biodegradable synthetic polymers have been widely utilized as biotherapeutic delivery scaffolds due to their tailorability in release, degradation, and mechanical properties and minimal variability during clinical translation 11,15,17,21‐23 .…”

Section: Introductionmentioning

confidence: 99%

“…Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology, and Clinical Translation for the regeneration of complex tissues [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] such as the rotator cuff enthesis. Traditionally, biodegradable synthetic polymers have been widely utilized as biotherapeutic delivery scaffolds due to their tailorability in release, degradation, and mechanical properties and minimal variability during clinical translation.…”

Section: Introductionmentioning

confidence: 99%

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Kinetic degradation and biocompatibility evaluation of polycaprolactone‐based biologics delivery matrices for regenerative engineering of the rotator cuff

Prabhath

Vernekar

Vasu

et al. 2021

J Biomedical Materials Res

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Whereas synthetic biodegradable polymers have been successfully applied for the delivery of biologics in other tissues, the anatomical complexity, poor blood supply, and reduced clearance of degradation byproducts in the rotator cuff create unique design challenges for implantable biomaterials. Here, we investigated lower molecular weight poly‐lactic acid co—epsilon‐caprolactone (PLA‐CL) formulations with varying molecular weight and film casting concentrations as potential matrices for the therapeutic delivery of biologics in the rotator cuff. Matrices were fabricated with target footprint dimensions to facilitate controlled and protected release of model biologic (Bovine Serum Albumin), and anatomically‐unhindered implantation under the acromion in a rodent model of acute rotator cuff repair. The matrix obtained from the highest polymeric‐film casting concentration showed a controlled release of model biologics payload. The tested matrices rapidly degraded during the initial 4 weeks due to preferential hydrolysis of the lactide‐rich regions within the polymer, and subsequently maintained a stable molecular weight due to the emergence of highly‐crystalline caprolactone‐rich regions. pH evaluation in the interior of the matrix showed minimal change signifying lesser accumulation of acidic degradation byproducts than seen in other bulk‐degrading polymers, and maintenance of conformational stability of the model biologic payload. The context‐dependent biocompatibility evaluation in a rodent model of acute rotator cuff repair showed matrix remodeling without eliciting excessive inflammatory reaction and is anticipated to completely degrade within 6 months. The engineered PLA‐CL matrices offer unique advantages in controlled and protected biologic delivery, non‐toxic biodegradation, and biocompatibility overcoming several limitations of commonly‐used biodegradable polyesters.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kinetic degradation and biocompatibility evaluation of polycaprolactone‐based biologics delivery matrices for regenerative engineering of the rotator cuff

Prabhath

Vernekar

Vasu

et al. 2021

J Biomedical Materials Res

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“…To accelerate bone regeneration, we utilized bone morphogenetic protein 2 (BMP-2), which is approved by the US FDA for a range of lumbar spinal fusion procedures and has been shown in ACL reconstruction models to enhance osteointegration of tendon grafts (16)(17)(18). In our previous study, we demonstrated that BMP-2 saline injections could enhance osteoid seam width and reduce bone tunnel cross-sectional area, a sign of bone regeneration (5).…”

Section: Significancementioning

confidence: 99%

Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits

Mengsteab

Otsuka

McClinton

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a “tiger graft.” The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.

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“…One of the most prevalent diseases that has been investigated in regenerative engineering studies is osteoarthritis (OA). Ongoing research in biomaterials and stem cell-based therapies has shown promising results in preclinical and clinical trials demonstrating that cartilage and bone regeneration could provide a long-term solution to OA and prevent progression to end-stage disease [4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Regenerative Engineering Animal Models for Knee Osteoarthritis

Esdaille

Ude

Laurencin

2021

Regen. Eng. Transl. Med.

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Osteoarthritis (OA) of the knee is the most common synovial joint disorder worldwide, with a growing incidence due to increasing rates of obesity and an aging population. A significant amount of research is currently being conducted to further our understanding of the pathophysiology of knee osteoarthritis to design less invasive and more effective treatment options once conservative management has failed. Regenerative engineering techniques have shown promising preclinical results in treating OA due to their innovative approaches and have emerged as a popular area of study. To investigate these therapeutics, animal models of OA have been used in preclinical trials. There are various mechanisms by which OA can be induced in the knee/stifle of animals that are classified by the etiology of the OA that they are designed to recapitulate. Thus, it is essential to utilize the correct animal model in studies that are investigating regenerative engineering techniques for proper translation of efficacy into clinical trials. This review discusses the various animal models of OA that may be used in preclinical regenerative engineering trials and the corresponding classification system. Lay Summary Osteoarthritis (OA) of the knee is the most common synovial joint disease worldwide, with high rates of occurrence due to an increase in obesity and an aging population. A great deal of research is currently underway to further our understanding of the causes of osteoarthritis, to design more effective treatments. The emergence of regenerative engineering has provided physicians and investigators with unique opportunities to join ideas in tackling human diseases such as OA. Once the concept is proven to work, the initial procedure for the evaluation of a treatment solution begins with an animal model. Thus, it is essential to utilize a suitable animal model that reflects the particular ailment in regenerative engineering studies for proper translation to human patients as each model has associated advantages and disadvantages. There are various ways by which OA can occur in the knee joint, which are classified according to the particular cause of the OA. This review discusses the various animal models of OA that may be used in preclinical regenerative engineering investigations and the corresponding classification system.

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Bone Regenerative Engineering Using a Protein Kinase A-Specific Cyclic AMP Analogue Administered for Short Term

Cited by 18 publications

References 65 publications

Kinetic degradation and biocompatibility evaluation of polycaprolactone‐based biologics delivery matrices for regenerative engineering of the rotator cuff

Kinetic degradation and biocompatibility evaluation of polycaprolactone‐based biologics delivery matrices for regenerative engineering of the rotator cuff

Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits

Regenerative Engineering Animal Models for Knee Osteoarthritis

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